bluuebunny/crossref_metadata_2025 huggingface dataset:
Developing the ambition for action in the Ocean Decade to 2030
Authors: Bassan Niccolo’ , Flamand Aude , Clausen Alison
Published: January 2025

The ocean is vital for regulating climate, supporting biodiversity, and sustaining human livelihoods. However, as climate change accelerates ocean acidification, deoxygenation, warming, and biodiversity loss, the ocean’s ability to provide solutions is at risk. Addressing critical gaps in ocean science is essential, and the United Nations Decade of Ocean Science for Sustainable Development 2021–2030 (the “Ocean Decade”) seeks to bridge these gaps. Its transformative framework is built around 10 key challenges representing urgent needs for ocean knowledge. The Vision 2030 process, initiated in the Decade’s third year, refines these challenges, setting quantifiable success measures by 2030. Informed by contributions from around 150 experts and 10 White Papers, the Vision 2030 process highlights priorities such as actively considering Indigenous knowledge, co-designing innovative solutions, and enhancing investment in ocean science. This article introduces the insights of the Vision 2030 process, emphasizing the need for inclusive, coordinated action across the science–policy–society interface. It underscores the urgency of prioritizing ocean health and securing sustainable financing for ocean initiatives, particularly as Sustainable Development Goal (SDG) 14 remains the least funded SDG. Through advancing knowledge, fostering innovation, and promoting inclusivity, the Ocean Decade aims to protect ocean ecosystems and ensure a sustainable future for future generations.
Regularity of the Solution to a Real Monge–Ampère Equation on the Boundary of a Simplex
Authors: Andreasson Rolf , Hultgren Jakob , Jonsson Mattias , Mazzon Enrica , McCleerey Nicholas
Published: January 2025

Motivated by conjectures in Mirror Symmetry, we continue the study of the real Monge–Ampère operator on the boundary of a simplex. This can be formulated in terms of optimal transport, and we consider, more generally, the problem of optimal transport between symmetric probability measures on the boundary of a simplex and of the dual simplex. For suitably regular measures, we obtain regularity properties of the transport map, and of its convex potential. To do so, we exploit boundary regularity results for optimal transport maps by Caffarelli, together with the symmetries of the simplex.
Range expansion of the tropical predatory crab Eurytium limosum (Say, 1818) (Decapoda: Brachyura: Panopeidae) into temperate salt marshes along the eastern coast of the United States
Authors: Silliman Parker D R , Zhang Y Stacy , Morton Joseph P
Published: January 2025

We document the range expansion of Eurytium limosum (Say, 1818), a panopeid, mud crab commonly found in Florida mangroves and in southeastern US salt marshes, from its historically known northern range limit in southern South Carolina to newly observed range in central North Carolina (NC) salt marshes. Through field surveys conducted in 2024, we recorded E. limosum populations in two salt marshes on Bogue Banks-Atlantic Beach, NC. Field surveys conducted in two salt marshes showed that this predatory crab is very abundant in both marshes, and its densities vary by marsh zone, with the highest abundance occurring in the low marsh. Compilation and analysis of published and unpublished data on mud-crab density in these same marshes reveal that E. limosum was not present in these marshes in the mid-1990’s but were at low densities in 2016, 88% lower than they were in 2024. Combined, these findings indicate a significant northward expansion (at least ~400 km) of E. limosum likely influenced by rising sea temperatures in NC. Given their current abundances and past studies that show this mesopedatory crab preys on two key salt marsh consumers, fiddler crabs and plant-grazing snails, and that it is an aggressive competitor, E. limosum will likely alter top-down forcing of marsh structure and function and/or competitive interactions with other infaunal marsh predators. We document what is likely the beginning of the tropicalization of the predator assemblage of temperate salt marshes, underscoring the importance of monitoring the distribution of marine species in response to climate change, and suggests potential impacts on local ecosystems and biodiversity that warrant future investigations.
Evaluation of a fluorophore for marking navel orangeworm (Lepidoptera: Pyralidae)
Authors: Liu Tzu-Chin (Jean) , Burks Charles S , Wilson Houston
Published: January 2025

Navel orangeworm, Amyelois transitella (Walker), is a key pest in California’s almonds, pistachios, and walnuts. This insect’s strong dispersal capacity can potentially undermine the efficacy of localized management efforts. The timing and extent of A. transitella movement between orchards remain unclear, and more studies are needed to better characterize its landscape ecology. Mark-release-recapture studies offer a potential solution but require a reliable insect marker that is durable, easily identifiable and has minimal impacts on A. transitella longevity and flight ability. To address this, we evaluated 4 colors (red, blue, green, and yellow) of a fluorophore marker (SmartWater) for adult A. transitella. We conducted laboratory assays to assess moth flight ability and mortality, as well as marker persistence over time using both quantitative (plate reader) and qualitative (visual observation) fluorophore detection methods. Results demonstrated that none of the 4 colors negatively affected A. transitella flight ability or mortality. Green and yellow markers were persistent and readily identified by both detection methods, unlike blue and red markers. Although marker degradation was observed over time with the quantitative method, a high percentage of moths (70.3%) retained green and yellow markers after 14 days. In contrast, these markers did not show significant degradation using the qualitative method, with over 94.2% of moths showing fluorescence 14 days postmarking. These findings highlight the strong potential of green and yellow markers for field studies with A. transitella. We discuss their use in future mark-release-recapture studies and compare the 2 fluorophore detection methods.
Vision Loss in an Infantryman With Complex Hearing Loss: Case Report and Review of Susac Syndrome
Authors: Lambert Lester H , Kernan Caroline J , Hartmann Kathryn M , O’Connell Stephen R , Powell Brittany E
Published: January 2025

Susac syndrome can resemble various disorders resulting in a delayed or missed diagnosis and subsequent delays in treatment. Here, we present how successful consideration of patient history, symptoms, and ancillary testing led to prompt diagnosis and treatment of Susac syndrome by ophthalmologists. A 27-year-old active duty infantryman presented with sudden vision loss in the right eye during strenuous exercise after experiencing similar symptoms in the left eye 5 months earlier. The patient’s medical history was notable for mixed conductive and sensorineural hearing loss, confounded by a history of concussions, syncope, frequent ear infections, tympanic membrane perforation requiring tympanoplasty, and loud noise exposures. Identification of branch retinal artery occlusions on fluorescein angiography and low-to-mid frequency hearing loss confirmed the diagnosis of Susac syndrome. The patient was immediately treated with high-dose oral prednisone and subsequently transitioned to rituximab infusions to preserve vision. Susac syndrome should be considered when a patient presents with vision loss, hearing deficits, and or cognitive changes, even if symptoms are separated by time and seemingly attributed to more common causes.
A skin-inspired durable de-icing surface with boosting interfacial cracks
Authors: Yang Qiucheng , Yang Jinlong , Hu Yuhao , Niu Xiaopeng , Liu Zhenda , Zou Jian , Guo Junchang , Xiong Hao , Gu Xingshi , Yang Li , Yu Fanfei , Zhu Shunpeng , Ye Ming , Yi Xian , Deng Xu
Published: January 2025

Fracture-based interfacial breakage has shown promise in efficiently removing ice accretion. Here, intrigued by the response of human skin to stress-induced deformation, we present a strategy to design tough-skin de-icing surfaces (TSDSs) that actively manipulate crack-induced ice-substrate interfacial breakage during ice removal. This design leverages the surface instability of thin films to generate extensive wrinkling at the ice-substrate interface, which serves as crack initiation sites. We demonstrate efficient ice shedding by creating wrinkles at two length scales: macro-wrinkles for actively initiating the cracks at the rim of the ice and micro-wrinkles for further promoting the stress concentration at the ice-substrate interface. The TSDS (τ < 10 kPa) displays excellent durability and weather resistance, achieving a large-area ice-self-shedding effect solely through gravity. The universality of the proposed mechanism is verified on multiple materials and potential applications. This design concept offers valuable insights into the creation of durable de-icing materials with enhanced ice-shedding properties.
Evaluation of resistant cultivars for management of downy mildew in fall cucumbers in South Deerfield, MA, 2024
Authors: Scheufele Susan B. , Higgins Genevieve , Shokoohi Alireza
Published: January 2025

Cucurbit downy mildew, caused by the oomycete pathogen Pseudoperonospora cubensis, is among the most devastating diseases of fall cucumber crops in the northeastern United States. Symptoms include angular, vein-trapped lesions on undersides of leaves that are initially water-soaked and develop fuzzy gray sporulation under humid conditions. Diseased foliage becomes quickly necrotic. This report evaluates the resistance to cucurbit downy mildew of 11 cucumber cultivars (Cucumis sativa ‘SVCS0415’, ‘SVCS0029’, ‘SVCS0025’, ‘TSX-CU254’, ‘TSX-CU252 AS’, ACU-2083’, TSX-CU253 AS’, ‘EWS-CU-059’, ‘Chaperon’, ‘Gateway’, and ‘Marketmore 76’). The trial was conducted in 2024 in South Deerfield, MA. Results from this trial will help cucumber growers select appropriate resistant cultivars for fall production, when downy mildew pressure is high.
Trends in Uterine Cancer Cases After the Coronavirus Disease 2019 (COVID-19) Pandemic
Authors: Tran Nathan , Chan Joshua E. , Stewart Chelsea , Johnson Caitlin R. , Darcy Kathleen , Tian Chunqiao , Kapp Daniel S. , Liao Cheng-I , Chan John K.
Published: January 2025

We assessed the temporal trends in diagnosis of uterine cancer before and during the coronavirus disease 2019 (COVID-19) pandemic using data from the United States Cancer Statistics database spanning from 2001 to 2020. A comparison between projected and observed new cases in 2020 revealed a 4,232-case discrepancy, indicating 9.3% fewer diagnosed cases than predicted based on trends. Hispanic and Asian and Pacific Islander patients exhibited the highest discrepancy at 14.6% and 12.0% fewer cases, respectively, compared with 8.6% and 6.9% for White and Black patients. Our results highlight the importance of targeting health resources toward vulnerable populations in an effort to address accumulated cases of uterine cases after the pandemic.
Barriers and Facilitators to Video Telehealth Use in Low-Income Hispanic Patients
Authors: Peterson Devan J. , de Haro Cristina M. , Kilgore David B. , Sorkin Dara H. , Gago-Masague Sergio , Billimek John
Published: January 2025

Background and Objectives:

As telehealth grows in ubiquity, it is important to understand the barriers and facilitators to telehealth utilization in historically marginalized populations. This study utilizes the Theory of Planned Behavior (TPB) to assess correlates of the intention to utilize video consultations among low-income Hispanic patients.

Methods:

This cross-sectional observational study included participants (N = 138) recruited from a federally qualified health center affiliated with a large university health system. Components of the TPB were assessed using an in-person survey. Participant survey responses were analyzed using multiple logistic regression to identify correlates of participants’ intention to utilize video consultations.

Results:

Multiple logistic regression revealed subjective norms (adjusted odds ratio (aOR [95% CI]) = 3.29 [1.66, 6.52], P = .001) as the only significant correlate of participants’ intention to utilize video consultations. Attitudes toward video consultations (aOR [95% CI] = 1.32 [0.60, 2.89], P = .49) and perceived behavioral control (1.72 [0.89, 3.32], P = .11) did not independently correlate with behavioral intention.

Conclusions:

Ratings of subjective norms were independently correlated with intention to utilize video consultations among low-income, predominantly Spanish-speaking Hispanic adults. These results suggest a potentially central role of relational influences in determining telehealth engagement in this population.
Association between hormone therapy and glioma risk in US women: a cancer screening trial
Authors: Pan Jinyu , Shao Chuan , Xu Chao , Zhang Gang , Jiang Haotian , Tang Tao , Tang Hui , Wu Nan
Published: January 2025

Objective

Gliomas are the most common primary brain tumors in adults, and the role of hormone therapy (HT) in their development remains controversial. This study with a cohort design aimed to investigate the association between HT use and glioma risk using the data from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial.

Methods

We analyzed data from 75,335 women, aged 50-78, who were enrolled between 1993 and 2001. The median follow-up period was 11.82 years. Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the relationship between HT use and glioma risk, adjusting for various potential confounders.

Results

Over the follow-up period, 101 participants were diagnosed with glioma. After adjusting for relevant variables, there was no significant association between HT use and glioma risk (HR, 1.16; 95% CI, 0.75-1.81). Similarly, no significant associations were found when considering HT status or duration of use. However, in subgroup analysis by education, marital status, body mass index, oral contraceptive, hysterectomy, ovariectomy, ever been pregnant, age at menarche, and age at menopause, we found that a significant positive association was only observed in the group with at least college graduate (HR, 3.00; 95% CI, 1.02-8.84). The interaction effect for education was not significant (P = 0.056)

Conclusions

Our findings suggest no overall link between HT use and glioma risk. Further research is needed to confirm these results.
Adjuvant transarterial chemoembolization for hepatocellular carcinoma following curative resection: A randomized, open-label, phase 3 trial
Authors: Ma Tao , Bai Xueli , Zhang Qi , Chen Wen , Huang Kaiquan , Qian Tao , Xu Yongzi , Sun Peiwei , Chen Yiwen , Xiao Wenbo , Sun Ke , Gao Shunliang , Liang Tingbo
Published: January 2025

Background and Aims:

The role of adjuvant transarterial chemoembolization (TACE) for HCC following curative resection remains controversial. We aimed to determine the effectiveness of postoperative adjuvant TACE in patients with HCC​​​​​.

Approach and Results:

In this randomized phase 3 trial, histologically confirmed patients with HCC (American Joint Committee on Cancer TNM stage I and II) were randomly assigned (1:1) to adjuvant TACE or observation groups. The primary endpoint was recurrence-free survival (RFS) in the intention-to-treat (ITT) population. The secondary endpoints included overall survival and safety. A total of 332 patients (ITT population) were randomly assigned to the TACE group (n=166) or the observation group (n=166) between March 2014 and June 2021. The RFS was comparable between the 2 groups from the ITT population (median, both unreached; HR, 0.88; 95% CI: 0.62–1.24; p=0.468). The RFS rates at 1, 3, and 5 years were 87.3% (95% CI: 81.2–91.5), 70.7% (95% CI: 63.0–77.0), and 60.6% (95% CI: 51.9–68.3) in the adjuvant TACE group and 84.8% (95% CI: 78.3–89.5), 69.3% (95% CI: 61.6–75.8), and 58.1% (95% CI: 49.5–65.8) in the observation group, respectively. The overall survival was comparable between the TACE group and the observation group in the ITT population (median, both unreached, HR, 1.06; 95% CI: 0.63–1.76; p=0.838). There was no grade ≥ 3 adverse event or treatment-related death in either group.

Conclusions:

Postoperative adjuvant TACE was not associated with prolonged RFS or overall survival in patients with American Joint Committee on Cancer TNM stage I or II HCC.
Refractive Changes and Corneal Thickness in Healthy Mountaineers at High Altitude: The Korzhenevskoi Experience (7105 m)
Authors: Panthier Christophe , Fabro Filippo , Debellemanière Guillaume , Gatinel Damien
Published: January 2025

Purpose:

The purpose of this study was to investigate the effect of hypoxia and hypobaric conditions on refraction and central corneal thickness on healthy corneas during an ascent without oxygen supplementation above 7000 m (23 000 ft).

Methods:

Twelve multinational mountaineers were included in a prospective observational cohort study during an expedition to the Korzhenevskoi Peak (7105 m). The two patients excluded from the study had a history with keratoconus or were current wearers of rigid contact lenses. None had a history of refractive surgery or ocular disease. The central corneal thickness (CCT), the oxygen saturation, and the refraction have been recorded for each patient using portable equipment. The highest measurement has been taken at 6356 m of altitude which is the highest ophthalmologic measurement ever done.

Results:

Longitudinal analysis revealed a significant increase of CCT during altitude exposure (CCTbaseline = 542± 36 μm; CCTC3 = 633 ± 30 μm) due to stromal edema reversible upon descent. The amount of decrease in oxygen saturation paralleled the increase in CCT. The refraction measurements showed a myopic shift (−1.14D) with the altitude (RBaseline = −0.41 ±2.25D; RC3 = −1.55 ± 2.41D P < 0.05).

Conclusions:

Significant stromal edema was found during exposure to high altitude in healthy mountaineers. This is due to hypoxia and decreased atmospheric pressure leading to a deficiency of adenosine triphosphate. A significant and clinically relevant myopic shift, due to the stroma edema, appears above 6500 m which can explained the blurry far vision in high altitude for mountaineers without oxygen supplementation.
The Effect of Autologous Serum Tears 50% on the Ocular Surface of Patients With Severe Dry Eye Disease due to Sjogren Syndrome: A Prospective, Double-Blind, Randomized, Controlled, Contralateral Eye Study
Authors: Bachtalia Konstantina , Plakitsi Athina , Voudouri Adamantia , Terzidou Chryssa , Dalianis Georgios , Kopsinis Gerasimos , Palioura Sotiria
Published: January 2025

Purpose:

To assess the impact of autologous serum (AS) tears at a 50% concentration on the ocular surface of patients with refractory dry eye disease (DED) because of Sjogren syndrome.

Methods:

Twenty eyes of ten patients with severe immune-mediated DED were contralaterally randomized to receive either AS tears 50% or artificial tears between June 2021 and May 2023. Changes in tear stability, ocular surface staining, and in the morphology of the corneal sub-basal nerves were evaluated before treatment and at 1, 2, and 3 months after treatment using objective tests for DED and confocal microscopy. The microbiological safety of the used AS tears 50% was investigated using Matrix-Assisted Laser Desorption Ionization–Time of Flight Mass Spectrometry.

Results:

The AS tears 50% group exhibited significant improvements in tear break-up time, Schirmer test scores, visual acuity, and confocal microscopy parameters of corneal nerve health at the 3-month follow-up (P < 0.05). Corneal nerve regeneration correlated with increased tear stability and decreased ocular surface staining. Microbiological analysis identified Gram-negative bacteria in the postuse AS tears, highlighting the need for meticulous handling and storage practices.

Conclusions:

Treatment with AS tears at a 50% concentration markedly enhances ocular surface health, tear stability, and visual acuity, affirming the regenerative effects on corneal nerves in severe DED. The findings advocate for the therapeutic potential of higher-concentration AS tears in DED management, albeit with strict protocols to mitigate contamination risks and ensure patient safety.
Injury induced endotheliopathy: overview, diagnosis, and management
Authors: Rehani Chavi , Abdullah Sarah , Kozar Rosemary Ann
Published: January 2025

Purpose of review

This review aims to examine recent advances in the understanding of injury-induced endotheliopathy and therapeutics to mitigate its development in critically injured patients.

Recent findings

Clinical studies have clearly demonstrated that syndecan-1 ectodomains can be found in circulation after various types of trauma and injury and correlates with worse outcomes. As the mechanisms of endotheliopathy are better understood, pathologic hyperadhesive forms of von Willebrand factor, along with a relative deficiency of its cleaving enzyme, a disintegrin and metalloprotease with thrombospondin type I motifs, member 13 (ADAMTS13), have emerged as additional biomarkers. Therapeutics to date have focused primarily on the protective effects of fresh frozen plasma and its constituents to restore the glycocalyx. Human recombinant ADAMTS13 holds promise, as do synthetic variants of heparan sulfate and activated protein C, although all data to date are preclinical.

Injury-induced endotheliopathy represents an important pathologic response to trauma. Key biomarkers, such as syndecan-1, can aid in the diagnosis, but testing is not yet available clinically. As the mechanisms of endotheliopathy are better understood, therapeutics are being identified and show promise. To date, plasma has been the most widely studied; however, like all therapeutics for injury-induced endotheliopathy, it has primarily been studied in the preclinical setting.
Developmental Venous Anomaly
Authors: Ngam Pei Ing , Anzai Yoshimi , Minoshima Satoshi
Published: January 2025

Developmental venous anomaly (DVA) is a common benign brain vascular malformation, typically asymptomatic, with intervention required when complications arise. We present the case of a 63-year-old man with mild cognitive decline whose brain FDG PET showed decreased uptake not only at the site of DVA, but in the extended surrounding parenchyma where MRI showed no parenchymal abnormalities. DVAs arise from developmental irregularities in the embryonic venous system, but likely affecting a greater extent of the surrounding parenchymal functions. These findings highlight the clinical significance of DVAs and their effects on the parenchymal function seen on FDG PET albeit normal parenchyma on structural imaging.
Metastatic Lung Lesion Changes in Follow-up Chest CT
Authors: Kenneth Portal Neta , Rochman Shalom , Szeskin Adi , Lederman Richard , Sosna Jacob , Joskowicz Leo
Published: January 2025

Purpose:

Radiological follow-up of oncology patients requires the detection of metastatic lung lesions and the quantitative analysis of their changes in longitudinal imaging studies. Our aim was to evaluate SimU-Net, a novel deep learning method for the automatic analysis of metastatic lung lesions and their temporal changes in pairs of chest CT scans.

Materials and Methods:

SimU-Net is a simultaneous multichannel 3D U-Net model trained on pairs of registered prior and current scans of a patient. It is part of a fully automatic pipeline for the detection, segmentation, matching, and classification of metastatic lung lesions in longitudinal chest CT scans. A data set of 5040 metastatic lung lesions in 344 pairs of 208 prior and current chest CT scans from 79 patients was used for training/validation (173 scans, 65 patients) and testing (35 scans, 14 patients) of a standalone 3D U-Net models and 3 simultaneous SimU-Net models. Outcome measures were the lesion detection and segmentation precision, recall, Dice score, average symmetric surface distance (ASSD), lesion matching, and classification of lesion changes from computed versus manual ground-truth annotations by an expert radiologist.

Results:

SimU-Net achieved a mean lesion detection recall and precision of 0.93±0.13 and 0.79±0.24 and a mean lesion segmentation Dice and ASSD of 0.84±0.09 and 0.33±0.22 mm. These results outperformed the standalone 3D U-Net model by 9.4% in the recall, 2.4% in Dice, and 15.4% in ASSD, with a minor 3.6% decrease in precision. The SimU-Net pipeline achieved perfect precision and recall (1.0±0.0) for lesion matching and classification of lesion changes.

Conclusions:

Simultaneous deep learning analysis of metastatic lung lesions in prior and current chest CT scans with SimU-Net yields superior accuracy compared with individual analysis of each scan. Implementation of SimU-Net in the radiological workflow may enhance efficiency by automatically computing key metrics used to evaluate metastatic lung lesions and their temporal changes.
Endoscopic Dacryocystorhinostomy in Nasolacrimal Duct Obstruction With and Without Dacryocystitis: A Comparative Study
Authors: Wei Jinfei , Li Xinyu , Zhou Guangming , Wu Wencan , Yu Bo
Published: January 2025

Aim:

This research was designed to make a comparison of the treatment outcomes of endoscopic dacryocystorhinostomy (En-DCR) in nasolacrimal duct obstruction (NLDO) with and without chronic dacryocystitis.

Methods:

NLDO (obstruction group) and chronic dacryocystitis (dacryocystitis group) patients treated with En-DCR in the Eye Hospital of Wenzhou Medical University from March 2021 to February 2022 were retrospectively analyzed. According to CT dacryocystography, patients in each group were assigned into the high obstruction group (obstruction located in the lacrimal sac) and the low obstruction group (obstruction located at or below the junction of the nasolacrimal duct and dacryocystis). The surgery outcomes of patients in the 2 groups were compared 12 months postoperation.

Results:

One hundred four patients (104 eyes: obstruction group: 49 eyes; dacryocystitis group: 55 eyes) were recruited. Patients with high obstruction accounted for 61.2% in the obstruction group and 32.7% in the dacryocystitis group. There were significantly more high obstruction patients in the obstruction group versus the dacryocystitis group (P<0.05). At 12 months postoperative follow-up, the total anatomic and functional success rate was 83.7% and 80.8%, respectively. Higher anatomic success rate (90.9%) and functional success rate (89.1%) were noted in the dacryocystitis group versus the obstruction group (75.5% and 71.4%, respectively, P<0.05).

Conclusions:

The obstruction site is higher in the obstruction group in comparison to that in the dacryocystitis group. En-DCR is effective in the treatment of NLDO and chronic dacryocystitis, and its efficacy on chronic dacryocystitis is better than that on NLDO.
Why wasn’t mirabegron chosen for the first year of the CMS negotiation program?
Authors: CADISH Lauren A. , SHEPHERD Jonathan P.
Published: January 2025

Importance: The most used overactive bladder (OAB) medications are anticholinergics, which professional societies recommend avoiding in older patients given dementia risk. Cost prevents patients from switching to preferred beta-3 agonists. Mirabegron was the only beta-3 agonist eligible for the Centers for Medicare/Medicaid Services (CMS) 2023 Drug Negotiation Program (DNP). While mirabegron’s price would be markedly reduced by inclusion in the DNP, only ten drugs were chosen in its first year.

Objectives: We sought to explain mirabegron’s absence from CMS’s 2023 DNP and estimate the percentage of anticholinergic to mirabegron conversions needed to merit DNP inclusion.

Study design: We modeled CMS's 2023 selection process using publicly available dashboards from 2017-2021. Among the 20 costliest drugs, we excluded ineligible drugs and categorized the remainder as DNP chosen/not chosen. For drugs not chosen, we used price inflation and beneficiary utilization trends to project total 2023 costs.

Results: In 2021, mirabegron was the 14th most costly drug overall—9th when excluding ineligibles—and the only top-20 drug eligible but not selected for the 2023 DNP. We estimated mirabegron to be 96.7% the cost of the 10th most costly drug. Switching 1.2% of 2021 anticholinergic prescriptions to mirabegron would have led to DNP inclusion, presenting an interesting dilemma where more patients would use mirabegron if it were cheaper, but insufficient patients used it for DNP inclusion to make it cheaper.

Conclusions: Mirabegron came exceedingly close to DNP selection in 2023, and its future inclusion in the DNP would likely herald a massive shift of Medicare patients away from anticholinergics.
High-throughput Mucus Microrheology for Phenotyping and Disease Modeling
Authors: Ling Feng , Sahin Ayse Tugce , Miller Naranjo Bernardo , Aime Stefano , Roth Doris , Tepho Niels , Vendrame Andrea S. , Emken Ellen , Kiechle Marion , Tesfaigzi Yohannes , Lieleg Oliver , Nawroth Janna
Published: January 2025

Mucus plays an integral role for the barrier function of many epithelial tissues. In the human airways, mucus is constantly secreted to capture inhaled microbes and pollutants and cleared away through concerted ciliary motion. Many important respiratory diseases exhibit altered mucus flowability and impaired clearance, contributing to respiratory distress and increased risk of infections. Understanding how mucus rheology changes during disease progression and in response to treatments is thus of great interest for subtyping patients and tailoring treatments, probing disease mechanisms, and tailoring therapies; however, basic research of mucus rheology is greatly hampered by the lack of scalable and user-friendly rheometry assays for the small volumes of mucus typically produced by in vitro respiratory models and in clinical ex vivo settings. To address this challenge, we developed a streamlined, high-throughput protocol leveraging Differential Dynamic Microscopy (DDM) to reliably measure the frequency-dependent microrheology of minuscule (3–10µL) mucus samples using standard epifluorescence microscopy. Our method does not require time-consuming user-interventions common in particle tracking routines and measures microrheology at the time scale of mucus relaxation (1-20s), hence greatly reducing assay time. We demonstrate the successful application of our method in mucus samples harvested from state-of-the-art air-liquid-interface (ALI) human respiratory cultures to assess mucus rheology in airway disease models and different culture conditions. To show that our approach equally applies to other types and sources of human mucus, we also validated our method with clinical samples of cervical mucus. We envision that our method can be seamlessly adopted by non-expert users, without the need for specialized equipment or extensive training, to study diseases and their treatments in the respiratory, intestinal, reproductive and other mucosal organ systems. This advancement opens up new avenues for large-scale studies, providing new insights into the role of mucus rheology which was previously limited by data accessibility and resource constraints.
Warming winters, changing springs: cold hardiness dynamics predict budbreak and associated low temperature threats on an intercontinental scale
Authors: Campos-Arguedas Francisco , Kirchhof Erica , North Michael G , Londo Jason P , Bates Terry , van Leeuwen Cornelis , Destrac-Irvine Agnès , Bois Benjamin , Kovaleski Al P
Published: January 2025

Temperate woody perennial plants form buds during late summer that contain leaves and flowers that emerge in the following growth season. To survive winter, dormant buds must attain cold hardiness, and timely lose it in spring to break bud while avoiding damage from low temperatures and late frosts. Here, we use an untrained process-based model to predict bud cold hardiness of three grapevine varieties (V. vinifera'Cabernet-Sauvignon' and 'Riesling', andV. hybrid'Concord') from historical temperature records of eight different locations in North America and Europe (n = 329). Based on those predictions, and thresholds of cold hardiness at budbreak from literature, timing of budbreak was extracted. Despite being untrained to the data, the RMSE of budbreak predictions was 7.3 days (Bias=−0.83). Based on cold hardiness estimations and air temperature records, low temperature damage was quantified and validated through newspapers and extension records. In years × location where damage was predicted, corrections to budbreak based on delays expected resulted in improvements of predictions (RMSE=7.2d, Bias=0.58). Predictions of instances of freeze damage risk demonstrate genotypic adaptation to different environments. At the species level, increasing or decreasing trends in freeze damage risk are predicted, depending on the range of mean dormant season temperature (MDST; 1 Nov - 30 Apr) present in each location. Sensitivity analysis of predicted time to budbreak based on MDST shows a general advancement of phenology at −5.8d/°C. However, in much warmer locations, delays can be expected as temperatures continue to increase (+1.9d/°C for MDST>10°C). Through cold hardiness dynamics, the estimation of chilling accumulation appears as an important source of error for predictions of spring phenology across environments. Cold dynamics represents an advancement in phenological modeling that provides information for the entirety of the dormant season, as well as budbreak.
Biomass Production, Phosphorus Use Efficiency, and Fatty Acid Composition in Phaeodactylum tricornutum Cultivated in Wastewater from an Atlantic Salmon Recirculating Aquaculture System
Authors: Borg-Stoveland Stian , Draganovic Vukasin , Gabrielsen Tove Margrethe , Spilling Kristian
Published: January 2025

Recirculating Aquaculture Systems (RAS) are becoming increasingly important as a sustainable method for fish production. However, further advancements are needed to enhance the sustainability of RAS, particularly in the management of waste-streams. Furthermore, the capital and operational expenditures of running a RAS is high, so solutions turning waste-streams into added value is a focus area for the industry moving forward. Wastewater is high in nitrogen, and phosphorus (P) is foreseen to be the limiting nutrient. Here we evaluated the growth dynamics, biomass production, nutrient uptake, phosphorus use efficiency (PUE), and fatty acid composition of the diatomPhaeodactylum tricornutumcultivated in aquaculture wastewater (AWW) from a land-based Atlantic salmon RAS. The diatom was cultivated in various treatments at pilot scale (10 L), including 100% AWW and AWW supplemented with silicon (Si) and P, and compared with a control treatment using Guillard's F/2 medium. The highest dry weight biomass concentrations of ~2.0 g L-1 was achieved for the nutrient-supplemented AWW treatments, even outcompeting the control, demonstrating its viability as a growth medium when supplemented with Si and P. The control treatment achieved the highest specific growth rate of 0.422 d-1. The "Si+P addition" treatment achieved the highest PUE, indicating that co-supplementation strategies can enhance phosphorus utilization. However, fatty acid yields, particularly eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), were lower in AWW-based treatments, likely due to micronutrient deficiencies or the effect of possible contaminants. Despite this,P. tricornutumcultivated in AWW offers a sustainable and possible cost-effective solution for producing biomass and valuable fatty acids.
RNA helicase DDX1 regulates germinal centre selection and affinity maturation by promoting tRNA ligase activity
Authors: Kimber Rachael , Ingelsfield Sarah , Screen Michael , Salerno Fiamma , Matheson Louise S , Okkenhaug Hanneke , Whale Alex , Assalaarachchi Jayalini , Stammers Melanie , Akdeniz Deniz , Andrews Simon , Ribeiro de Almeida Claudia
Published: January 2025

Clonal expansion of antigen-specific B-cells defines effective germinal centre responses and is key for the generation of high-affinity antibodies. While positive selection in germinal centres has been associated with anabolic metabolism and cell growth, the downstream drivers of B-cell proliferation are not well understood. Here we report that the RNA helicase DDX1 is required for germinal centre maturation and accrual of dark-zone cellularity. Upon interaction with T-follicular helper cells, DDX1-deficient B-cells upregulate c-MYC but do not clonally expand. We show that positive selection is coupled with an increase in mRNA translation, that is dependent on DDX1. DDX1 endows B-cells with the protein biosynthetic capability that is required for rapid cell proliferation. It does so by modulating the activity of the tRNA ligase complex and tRNA splicing. Our data reveal that mRNA translation efficiency is a key determinant of B-cell fitness during germinal centre responses.
scValue: value-based subsampling of large-scale single-cell transcriptomic data for machine and deep learning tasks
Authors: Huang Li , Gong Weikang , Chen Dongsheng
Published: January 2025

Large single-cell RNA-sequencing (scRNA-seq) datasets offer unprecedented biological insights but pose major computational challenges for visualisation and analysis. Existing subsampling methods can improve efficiency yet may not guarantee downstream machine and deep learning (ML/DL) performance. Here, we propose scValue, a conceptually distinct approach that ranks individual cells by "data value" based on out-of-bag estimates from a random forest. scValue prioritises higher-value cells and allocates more representation to cell types displaying greater value variability, preserving essential biological signals in subsamples. We benchmarked scValue in automatic cell-type annotation tasks on four large datasets (human peripheral blood mononuclear cells, mouse brain cells, human cross-tissue atlas, and mouse aging cell atlas), paired with distinct ML/DL models (scANVI, scPoli, CellTypist, and ACTINN). Our method consistently outperformed existing subsampling methods, closely matching full-data performance in all annotation tasks. Furthermore, in two additional case studies of label transfer learning (via CellTypist) and cross-study label harmonisation (via CellHint), scValue better preserved T-cell annotations across human gut-colon datasets and more accurately reproduced T-cell subtype relationships in a human spleen dataset. Finally, using 16 public datasets ranging from tens of thousands to millions of cells, we compared subsampling quality of scValue and its counterparts on computational time, Gini coefficient, and Hausdorff distance. The method demonstrated fast execution, balanced cell-type representation, and near-random subsampling distributional characteristics. Overall, scValue provides an efficient and accurate solution for subsampling large scRNA-seq data for ML/DL tasks. It is implemented as an open-source Python package installable via pip, with source code available at https://github.com/LHBCB/scvalue.
Real-time simultaneous monitoring of multiple analytes in bacterial cultures
Authors: Fink Maggie M , Aljuboori Zahra , Klaers Maggie , Underdue Morgan , Malkovsky Joseph , Rizk Shahir S
Published: January 2025

Bacterial metabolites are essential for biological processes, influencing human health, ecosystems, and industrial applications. Simultaneous real-time monitoring of these metabolites is critical in understanding microbial dynamics, particularly in bioreactors and food or drug manufacturing. Current approaches often rely on offline methods, which are labor-intensive and susceptible to contamination, or genetic engineering techniques limited to single-analyte monitoring. Here, we present a novel method utilizing engineered periplasmic binding proteins (PBPs) conjugated with fluorophores to track multiple metabolites simultaneously in Escherichia coli cultures. This system continuously monitors the levels of multiple analytes such as glucose, arabinose, ribose, glutamate, and arginine, providing high temporal resolution while maintaining sensor stability over 24 hours. Our findings confirm hierarchical substrate utilization in E. coli and demonstrate the versatility of PBP-based multi-sensor arrays. This approach offers a non-invasive, modular, and scalable tool for bacterial metabolite analysis, paving the way for advances in both fundamental discoveries and practical applications in microbiology.
Atlas of plasma metabolic markers linked to human brain morphology
Authors: van der Meer Dennis , Kopal Jakub , Shadrin Alexey , Fuhrer Julian , Rokicki Jaroslav , Stinson Sara , Djurovic Srdjan , Dale Anders , Andreassen Ole
Published: January 2025

Background: Metabolic processes form the basis of the development, functioning and maintenance of the brain. Despite accumulating evidence of the vital role of metabolism in brain health, no study to date has comprehensively investigated the link between circulating markers of metabolic activity and in vivo brain morphology in the general population. Methods: We performed uni- and multivariate regression on metabolomics and MRI data from 24,940 UK Biobank participants, to estimate the individual and combined associations of 249 circulating metabolic markers with 91 measures of global and regional cortical thickness, surface area and subcortical volume. We investigated similarity of the identified spatial patterns with brain maps of neurotransmitters, and used Mendelian randomization to uncover causal relationships between metabolites and the brain. Results: Intracranial volume and total surface area were highly significantly associated with circulating lipoproteins and glycoprotein acetyls, with correlations up to .15. There were strong regional associations of individual markers with mixed effect directions, with distinct patterns involving frontal and temporal cortical thickness, brainstem and ventricular volume. Mendelian randomization provided evidence of bidirectional causal effects, with the majority of markers affecting frontal and temporal regions. Discussion: The results indicate strong bidirectional causal relationships between circulating metabolic markers and distinct patterns of global and regional brain morphology. The generated atlas of associations provides a better understanding of the role of metabolic pathways in structural brain development and maintenance, in both health and disease.
Epidemiological Burden and Projections of Pulmonary Arterial Hypertension in China: An Analysis from the Global Burden of Disease Study 2021
Authors: Wei Shuoshuo , Han Yonghui , Liu Min , Wang Hanli , Lu Zhiwei , Cheng Yusheng , Guo Jun , Zha Lei
Published: January 2025

Objective: Pulmonary arterial hypertension (PAH) is a severe condition with high morbidity and mortality, yet its epidemiology in China remains poorly understood. This study aims to assess the burden of PAH in China from 1990 to 2021 and project trends to 2050, providing insights for effective management and prevention strategies. Method: Data from the Global Burden of Disease (GBD) Study 2021 were analyzed, focusing exclusively on PAH. Key metrics included incidence, prevalence, mortality, and disability-adjusted life years (DALYs), along with their corresponding age-standardized rates (ASRs). Average annual percent changes (AAPCs) were calculated using joinpoint regression analysis, and a Bayesian age-period-cohort model was employed to project trends through 2050. Results: In 2021, there were 41,135 estimated prevalent cases of PAH (95% UI: 32,838.91 to 51,357.25) in China, with an age-standardized prevalence rate (ASPR) of 2.24 per 100,000. Females accounted for approximately 58% of cases. PAH caused 7,318 deaths (95% UI: 4,835.72 to 9,075.75; 3,683 males, 3,635 females), with an age-standardized death rate (ASDR) of 0.42 per 100,000. From 1990 to 2021, the ASPR increased slightly from 2.07 (95% UI: 1.68 to 2.54) to 2.24 (95% UI: 1.81 to 2.75), while the ASDR decreased from 0.61 (95% UI: 0.46 to 0.83) to 0.42 (95% UI: 0.28 to 0.51). Projections suggest declining trends in both ASPR and ASDR, although the overall prevalence of PAH is expected to rise over the next 30 years. Conclusion: PAH imposes a significant disease burden in China, particularly among women and older adults. These findings highlight the urgent need to enhance diagnostic capabilities and develop improved treatment strategies to address this challenging condition in the Chinese population.
Proteomic profiling of zinc homeostasis mechanisms inPseudomonas aeruginosathrough data-dependent and data-independent acquisition mass spectrometry
Authors: Meyer Annaliese C. S. , McIlvin Matthew R. , Lopez Paloma , Searle Brian C. , Saito Mak A.
Published: January 2025

Zinc is central to the function of many proteins, yet the mechanisms of zinc homeostasis and their interplay with other cellular systems remain underexplored. In this study, we employ data-dependent acquisition (DDA) and data-independent acquisition (DIA) mass spectrometry to investigate proteome changes inPseudomonas aeruginosaunder conditions of different zinc availability. Using these methods, we detected 2143 unique proteins, 1578 of which were identified by both DDA and DIA. We demonstrated that most of the previously described Zn homeostasis systems exhibit proteomic responses that follow similar trends to those seen in transcriptomics studies. However, some proteins that are considered instrumental in Zn homeostasis, notably those in Zn transporter ZnuABC, were not detected by our methods, although other proteins of other uptake systems were abundant. Furthermore, changes in abundance of multiple Zn-metalloproteins and Zn-independent homologs were clearly observable, with respective increases and decreases when Zn was provided, though the magnitude of these changes varied. Most of the Zn-metalloproteins observed were located in one of two Zur-regulated operons between PA5534 and PA5541. This study provides a view of Zn homeostasis mechanisms that is complementary to existing transcriptomics investigations: as gene transcripts are not strictly proportional to the actual distribution of proteins within a cell, analysis of the proteome offers another way to assess the relative use and importance of similar or ostensibly redundant systems in different conditions and can highlight shifts in metal prioritization between metalloproteins.
Manifestation of antiquark nuggets in collisions with the Earth
Authors: Flambaum V. V. , Samsonov I. B. , Vong G. K.
Published: January 2025

Antiquark nuggets are hypothetical compact composite objects conjectured to account for a significant fraction of dark matter in the Universe. In contrast to quark nuggets, these objects consist of antimatter. They may remain undetected if they possess a sufficiently small cross section relative to their mass. In this paper, we investigate the allowed region in the parameter space of this model that is consistent with the observed neutrino flux from the Sun and the Earth, and the nonobservation of seismic events with specific signatures of dark matter particles. We found the allowed values of the antibaryon charge number in this model to be in the interval 2×1024<A<8×1025, while the probability of nucleon annihilation upon collisions with the antiquark core is constrained by 0.1≲κ<0.25. These values of A and κ are, however, constrained by the IceCube experiment and nonobservation of impacts of antiquark nuggets on humans. Although very large values of the antibaryon charge, A>1033, are not fully excluded by the present study, we show that they conflict with the nonobservation of rare catastrophic explosionlike events on the Earth.

Published by the American Physical Society
2025