bluuebunny/crossref_metadata_2025_split huggingface dataset:
Symptoms Associated With Gadolinium Exposure
Authors: Shahid Imran , Lancelot Eric 
Published: February 2025

Objective
Some patients who received multiple administrations of gadolinium-based contrast agents (GBCAs) have been reported to develop “symptoms associated with gadolinium exposure” (SAGE). The aim of this study was to analyze pharmacovigilance data and to explore the various SAGE patterns of linear and macrocyclic GBCAs among patients exhibiting 3 or more SAGE symptoms.

Materials and Methods
SAGE were identified from a review of the scientific literature, and the corresponding preferred terms (PTs) were searched in each system organ class recorded in the FDA Adverse Event Reporting System (FAERS). To ensure the comparability of data, 3 macrocyclic and 3 linear extracellular GBCAs currently approved for intravenous administration in the United States were considered. Only patients with 3 or more SAGE symptoms were included. SAGE weights, representing the percentage of SAGE symptoms among all adverse events collected over a 6-year period from 2014 to 2019, were calculated for each GBCA. The frequency of these symptoms to occur in sets of “3 PT combinations” was also analyzed. The 3 PT combinations were calculated by first selecting the PT with the highest occurrence for a GBCA and then combining it with all the PTs accounting for 5% or more of the total adverse events reported for the respective GBCA. This led to identify the most prevalent 3 PT combinations per GBCA. Moreover, in order to determine whether or not SAGE symptoms were specific to GBCAs, data for 4 water-soluble iodinated contrast media were also extracted from the FAERS database over the same period, using the SAGE list of symptoms as reference.

Results
The analysis of FAERS data revealed a significantly higher SAGE weight for the linear GBCAs (20%–24%) than for the macrocyclic GBCAs (5%–9%). For the linear agents, the most prevalent 3 PT combinations of SAGE symptoms were reported in 152–164 occurrences, whereas for the macrocyclic agents, this range was significantly lower (1–13 occurrences). Moreover, all these agents could be categorized in 3 groups with different patterns of 3 PT combinations (ie, [gadodiamide and gadopentetate dimeglumine], [gadobenate dimeglumine and gadoteridol], and [gadoterate dimeglumine and gadobutrol]). The most prevalent PTs were found to be “pain,” “arthralgia,” and “headache” in each group, respectively.

Conclusions
The global SAGE weights were significantly lower for the macrocyclic GBCAs as compared with the linear GBCAs. Moreover, the frequency of occurrence of 3 PT combinations was notably lower with the macrocyclic agents and comparable to the iodinated contrast media, indicating that SAGE may be negligible for this class of GBCAs. Different patterns of 3 PT combinations were also observed among the GBCAs involved in this study. A causal relationship could not be established between SAGE and the corresponding GBCAs, therefore, further research on this topic and routine pharmacovigilance are warranted.
Long-range electrostatic forces govern how proteins fold on the ribosome
Authors: Streit Julian O. , Chan Sammy H.S. , Burridge Charles , Wallace Joel , Waudby Christopher A. , Cabrita Lisa D. , Christodoulou John 
Published: February 2025

AbstractProtein biosynthesis and folding are tightly intertwined processes regulated by the ribosome and auxiliary factors. Nascent proteins can begin to fold on their parent ribosome but formation of the native state is often inhibited well beyond the emergence of the necessary residues from the exit tunnel. The dominant forces driving this apparent destabilisation have remained unclear. We investigate this here, combining NMR experiments and atomistic simulations of a folded nascent chain on and off the ribosome. While its native structure and internal dynamics remain unaltered, co-translational folding is disfavoured due to intermolecular electrostatic repulsion between the negatively charged ribosome surface and nascent protein. Partially folded intermediates are less destabilised, resulting in their high populations. Specifically, we show that the polypeptide’s net charge is the dominant factor determining nascent folding thermodynamics, with smaller contributions from charge distribution. Consequently, positively charged proteins can fold on the ribosome without populating stable intermediates. These findings reconcile conflicting observations of previous studies and establish the general physical principles underpinningde novoprotein folding.
Probing the Role of Membrane in Neutralizing Activity of Antibodies Against Influenza Virus
Authors: Ozgulbas Defne G. , Tan Timothy J. C. , Wen Po-Chao , Teo Qi Wen , Lv Huibin , Ghaemi Zhaleh , Frank Martin , Wu Nicholas C. , Tajkhorshid Emad 
Published: February 2025

SUMMARYInfluenza poses a major health issue globally. Neutralizing antibodies targeting the highly conserved stem region of hemagglutinin (HA) of the influenza virus provide considerable protection against the infection. Using an array of advanced simulation technologies, we developed a high-resolution structural model of full-length, Fab-bound HA in a native viral membrane to characterize direct membrane interactions that govern the efficacy of the antibody. We reveal functionally important residues beyond the antibody’s complementary-determining regions that contribute to its membrane binding. Mutagenesis experiments and infectivity assays confirm that deactivating the membrane-binding residues of the antibody decreases its neutralization activity. Therefore, we propose that the association with the viral membrane plays a key role in the neutralization activity of these antibodies. Given the rapid evolution of the influenza virus, the developed model provides a structural framework for the rational design and development of more effective therapeutic antibodies.
A century of theories of balancing selection
Authors: Ruzicka Filip , Zwoinska Martyna K. , Goedert Debora , Kokko Hanna , Richter Xiang-Yi Li , Moodie Iain R. , Nilén Sofie , Olito Colin , Svensson Erik I. , Czuppon Peter , Connallon Tim 
Published: February 2025

AbstractTraits that affect organismal fitness are often very genetically variable. This genetic variation is vital for populations to adapt to their environments, but it is also surprising given that nature (after all) “selects” the best genotypes at the expense of those that fall short. Explaining the extensive genetic variation of fitness-related traits is thus a longstanding puzzle in evolutionary biology, with cascading implications for ecology, conservation, and human health. Balancing selection—an umbrella term for scenarios of natural selection that maintain genetic variation— is a century-old explanation to resolve this paradox that has gained recent momentum from genome-scale methods for detecting it. Yet evaluating whether balancing selection can, in fact, resolve the paradox is challenging, given the logistical constraints of distinguishing balancing selection from alternative hypotheses and the daunting collection of theoretical models that formally underpin this debate. Here, we track the development of balancing selection theory over the last century and provide an accessible review of this rich collection of models. We first outline the range of biological scenarios that can generate balancing selection. We then examine how fundamental features of genetic systems—including non-random mating between individuals, differences in ploidy, genetic drift, and different genetic architectures of traits— have been progressively incorporated into the theory. We end by linking these theoretical predictions to ongoing empirical efforts to understand the evolutionary processes that explain genetic variation.
Real-world brain imaging in a population-based cohort enables accurate markers for dementia
Authors: Sund Reijo , Seppänen Juho , Moradi Elaheh , Väänänen Sami , Miettinen Jani , Hakumäki Juhana , Rikkonen Toni , Kröger Heikki , Koivumaa-Honkanen Heli , Solomon Alina , Tohka Jussi ,   Alzheimer’s Disease Neuroimaging Initiative
Published: February 2025

AbstractINTRODUCTIONWhile a vast amount of MRI data are collected for healthcare delivery, generating real-world evidence (RWE) in Alzheimer’s and related diseases (ADRD) research is substantially limited by lack of methods and results showing how routine MRIs can be used for ADRD imaging studies.METHODSWe compared three established ADRD biomarkers (total gray matter, hippocampal and ventricular volumes) in four groups (normal, subjective complaints, mild cognitive impairment, and dementia) between the general population of women born in 1932-1941 in the Kuopio region of eastern Finland (population-based OSTPRE cohort, N=14220) and a well-characterized research cohort (ADNI).RESULTSA total of 2434 brain MRIs for 1885 women were collected between 2003-2022 by the public healthcare provider covering all residents in the region. The established biomarkers were overall aligned between these cohorts.DISCUSSIONTypical biomarkers extracted from real-world brain MRI scans collected over 20 years are suitable for generating RWE in ADRD research.HighlightsReal-world brain MRI is applicable for generating evidence in ADRD researchFirst study comparing a real-world MRI cohort with an established research cohort referenceA methodological framework for RWE ADRD studies using routinely collected MRIs
Neoadjuvant chemotherapy response and genetic susceptibility in recently parous women with breast cancer
Authors: Dennis Saya , Tsukioki Takahiro , Kocherginsky Masha , Qi Andrea Keya , DeHorn Sarah , Gurley Michael , Wrubel Erica , Luo Yuan , Khan Seema Ahsan 
Published: February 2025

AbstractIntroductionWomen with recent parity are at increased short-term breast cancer (BC) risk and face a worse prognosis. The effect of parity on response to neoadjuvant chemotherapy (NAC) is unstudied, and the influence of inherited susceptibility on parity-related short-term risk remains unclear.MethodsWe conducted a retrospective case-cohort study among women aged ≤50 with non-metastatic BC diagnosed between 2010 and 2020 who underwent genetic testing and were treated at Northwestern Medicine. Associations between NAC response and recency of parity were evaluated using multivariate logistic regression, stratified by tumor biologic subtypes. Relationships between germline mutations, recency of parity, and BC were explored via multi-state modeling and linear regression.ResultsAmong 1,080 eligible women, 231 received NAC. Treatment response was poorer in parous women with triple negative tumors compared to nullipara, regardless of the recency of parity (P<0.03). Among 122 women (11.3%) with detectable pathogenic mutations, adjusted analyses with both modeling approaches revealed no indications thatBRCA1/2carriers had an increased hazard of BC diagnosis in the decade following recent parity, compared to nulliparous mutation carriers. ForBRCA2andPALB2carriers, breast cancer diagnosis occurred less frequently in the post-partum intervals.ConclusionWe observed a poor response to NAC in parous TNBC patients compared to nullipara; effects of immunotherapy-based regimens deserve evaluation in the context of parity. Post-partum BC occurrence is not increased inBRCA1/2carriers; effects of rarer susceptibility genes may differ. These important effects of parity on BC in young women and those at genetic risk warrant larger prospective studies.
MMR vaccination coverage in the U.S. before and after the COVID-19 pandemic: A modelling study
Authors: Dong Ensheng , Nearchou Andreas , Okura Yamato , Saiyed Samee , Gardner Lauren M. 
Published: February 2025

BackgroundChildhood vaccination rates have been declining in the United States since the COVID-19 pandemic began. While COVID-19 exacerbated the decline in routine vaccination through disruption of healthcare services and the diversion of resources, factors including vaccine hesitancy, socioeconomic disparities and vaccine policy also contribute to changes in vaccination behavior. Understanding the factors that influence vaccination choice is necessary to develop effective public health policy.MethodsWe collect county-level MMR vaccination rates for kindergarten children from 2017 – 2024 for 2,266 U.S. counties, evaluate coverage patterns and trends before and after the COVID-19 pandemic, and implement multivariable weighted logistic regression models to identify factors associated with low and declining MMR vaccination rates in U.S. counties.FindingsWe reveal a nationwide decline in MMR rates following the COVID-19 pandemic, with declines observed in 1,688 of the counties evaluated. We find state-level non-medical exemption (NME) policies to be strongly associated with low and declining MMR rates. We identify a positive association in vaccination rates across vaccine types. We find higher MMR rates are positively associated with Republican-aligned counties and declines in MMR rates to be positively associated with COVID-19 death rates.InterpretationThe significant association between NMEs and low and declining MMR rates suggest these state level policies are harmful and reduce vaccination coverage. The positive associations among vaccine types suggest spillover effects in vaccine seeking behavior. The association between MMR rates and Republican-aligned counties contrast COVID-19 vaccination patterns, highlighting the complex nature of political polarization on vaccine-related behavior, while the association between MMR declines and COVID-19 death rate reveals an additional burden posed by the pandemic.FundingThis work was supported by a grant from Bloomberg Philanthropies awarded to the Johns Hopkins Bloomberg Center for Government Excellence, City Analytics Initiative.
Estimating health facility-level catchment populations using routine surveillance data and a Bayesian gravity model
Authors: Millar Justin , Arambepola Rohan , Cameron Ewan , Hamainza Busiku , Silumbe Kafula , Miller John , Bennett Adam , Slater Hannah 
Published: February 2025

AbstractAccurate estimates of health facility catchment populations are crucial for understanding spatial heterogeneity in disease incidence, targeting healthcare interventions, and allocating resources effectively. Despite improvements in health facility reporting, reliable catchment population data remain sparse. This study introduces a Bayesian gravity model-based approach for estimating catchment populations at health facilities, with a focus on Zambia’s routine malaria surveillance data from 2018-2023. Our method integrates health-seeking behavior, facility attractiveness, and travel time, allowing for the development of probabilistic catchment areas that reflect the treat-seeking and facility selection process. We developed an open-source R package to implement this method, and we apply this model to Zambian health facilities and compare the results to reported headcount data, highlighting improvements in stratification of malaria incidence rates. Additionally, we validate the model’s sensitivity using real-world treatment-seeking data from household surveys in Southern Province, Zambia, demonstrating its utility in enhancing sub-district-level health facility data for strategic planning. Validation of model facility selection rates compared to the treatment-seeking data showed a model sensitivity of 0.72 overall, with sensitivity reaching 0.89 for households within 2 kilometers of their preferred facility. This validation supports the model’s ability to closely estimate treatment-seeking behavior patterns, offering a scalable, accurate tool for enhancing local-level decision-making for health interventions, contributing to improved targeting and understanding of healthcare access patterns.
Evaluation of an Integrated Digital and Mobile Intervention for COPD Exacerbation
Authors: O’Connor Laurel , Wang Biqi , Ye Zehao , Behar Stephanie , Tarrant Seanan , Stamegna Pamela , Pretz Caitlin , Soni Apurv 
Published: February 2025

AbstractBackgroundChronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and healthcare utilization, with frequent exacerbations contributing to emergency department visits and hospitalizations. This study evaluates a multimodal, community-based digital health intervention’s association with changes in acute care utilization among patients with COPD to develop preliminary estimates of intervention effects.MethodsIn this decentralized, nonrandomized pilot clinical trial, participants with moderate to severe COPD were offered biometric monitoring, symptom tracking, on-demand MIH services, and a digital pulmonary rehabilitation program. Outcomes were compared between intervention participants and a weighted synthetic control group using full optimal matching. Weighted odds ratios derived from regression models were used to estimate intervention effect size. The primary outcome was hospitalization during the study period. Secondary outcomes included 30 and 90-day readmission rates, emergency department visits, and hospital length of stay.ResultsIn total, 88 participants from the intervention arm (mean age 67, 50% female) were compared to a weighted synthetic control of 14,492 participants (weighted mean age 66, 48.7% female). We observed that participants in the intervention arm had a trend toward decreased hospitalization with an OR of 0.69 (CI 0.44-1.03, p=0.066). The intervention was also associated with 61% decreased odds of 30-day readmission after an index admission compared to controls (OR: 0.39, 95% CI: 0.16–0.95, p = 0.04). Trends toward reductions in ED visits and hospital length of stay were also observed.ConclusionsA combined digital and mobile health approach to COPD management was associated with reductions in acute care utilization. These findings support further investigation into hybrid care models to enhance COPD self-management and improve patient outcomes. Future research should evaluate scalability, cost-effectiveness, and long-term clinical impact.
Identifying single origin rare variants in population genomic data
Authors: Reynolds Josh J. , Koufopanou Vassiliki , Burt Austin 
Published: February 2025

AbstractGenomic analyses have shown that some mutations in large population genomic datasets may be the result of repeated, independent events at the same locus. However, the possibility of this recurrent mutation is often ignored, even when it has the potential to introduce errors, such as when assuming co-ancestry through variant sharing for demographic analysis. Even rare variants such as doubletons, which should be particularly informative about recent demography, may have multiple origins despite arising relatively recently in the population. Here, we develop methods first to estimate the frequency of recurrent doubletons in a population genomic dataset from the occurrence of tri-allelic sites with two different singleton mutations, and then to identify a subset of high confidence single origin doubletons based on the presence of a linked rare variant on the surrounding shared haplotype. Applying these methods to data for the malaria mosquitoAnopheles gambiae, we estimate that up to ∼16% of reported doubletons have independent origins. We then identify a set of doubletons likely (∼99%) to have a single origin, which consists of ∼68% of all the expected single origin doubletons (and ∼57% of all observed doubletons). The effectiveness of our approach is queried, and these doubletons are then used to test population genetic hypotheses about recombination, selection, and isolation by distance. The methods developed here should be useful for demographic inference when populations are large enough such that recurrent mutation cannot be ignored.
Commissioning of a compact multibend achromat lattice NanoTerasu: A new 3 GeV synchrotron radiation facility
Authors: Obara Shuhei , Ueshima Kota , Asaka Takao , Hosaka Yuji , Kan Koichi , Nishimori Nobuyuki , Aoki Toshitaka , Asano Hiroyuki , Haga Koichi , Iba Yuto , Ihara Akira , Ito Katsumasa , Iwashita Taiki , Kadowaki Masaya , Kanahama Rento , Kobayashi Hajime , Kobayashi Hideki , Nishihara Hideo , Nishikawa Masaaki , Oikawa Haruhiko , Saida Ryota , Sakuraba Keisuke , Sugimoto Kento , Suzuki Masahiro , Takahashi Kouki , Takahashi Shunya , Tanaka Tatsuki , Tsuchiyama Tsubasa , Yoshioka Risa , Aoki Tsuyoshi , Dewa Hideki , Fujita Takahiro , Kawase Morihiro , Kiyomichi Akio , Hamano Takashi , Masaki Mitsuhiro , Masuda Takemasa , Matsubara Shinichi , Okada Kensuke , Saji Choji , Taniuchi Tsutomu , Taniuchi Yukiko , Ueda Yosuke , Yamaguchi Hiroshi , Yanagida Kenichi , Fukami Kenji , Hosoda Naoyasu , Ishii Miho , Itoga Toshiro , Iwai Eito , Magome Tamotsu , Oishi Masaya , Ohshima Takashi , Kondo Chikara , Sakurai Tatsuyuki , Shoji Masazumi , Sugimoto Takashi , Takano Shiro , Tamura Kazuhiro , Watanabe Takahiro , Tomai Takato , Azumi Noriyoshi , Inagaki Takahiro , Maesaka Hirokazu , Takahashi Sunao , Tanaka Takashi , Inoue Shinobu , Kumazawa Hirosuke , Moriya Kazuki , Sakai Kohei , Seno Toshio , Sumitomo Hiroshi , Takesako Ryoichi , Tanaka Shinichiro , Yamamoto Ryo , Yokomachi Kazutoshi , Yoshioka Masamichi , Hara Toru , Matsui Sakuo , Hiraiwa Toshihiko , Tanaka Hitoshi , Ego Hiroyasu 
Published: February 2025

NanoTerasu, a new 3 GeV synchrotron light source in Japan, began user operation in April 2024. It provides high-brilliance soft to tender x-rays and covers a wide spectral range from ultraviolet to tender x-rays. Its compact storage ring with a circumference of 349 m is based on a four-bend achromat lattice to provide two straight sections in each cell for insertion devices with a natural horizontal emittance of 1.14 nm rad, which is small enough for soft x-rays users. The NanoTerasu accelerator incorporates several innovative technologies, including a full-energy injector C-band linear accelerator with a length of 110 m, an in-vacuum off-axis injection system, a four-bend achromat with B-Q combined bending magnets, and a TM020-mode accelerating cavity with built-in higher-order-mode dampers in the storage ring. This paper presents the accelerator machine commissioning over a half-year period and our model-consistent ring optics correction. The first user operation with a stored beam current of 160 mA is also reported. We summarize the storage ring parameters obtained from the commissioning. This is helpful for estimating the effective optical properties of synchrotron radiation at NanoTerasu.

Published by the American Physical Society
2025