bluuebunny/crossref_metadata_2025 huggingface dataset:
Indirect effects of the COVID-19 pandemic on healthcare contacts, quality of care, and social disparities across essential healthcare domains
Authors: Knudsen Søren Valgreen , Jensen Henry , Mainz Jan , Baandrup Lone , Gögenur Ismail , Jensen Jens Winther , Johnsen Søren Paaske , Lassen Jens Flensted , Løkke Anders , Mackenhauer Julie , Mortensen Laust Hvas , Møller Henrik , Olesen Tina Bech
Published: February 2025

Background

The COVID-19 pandemic significantly affected global healthcare systems, revealing their resilience to crises. Despite this, national-level research on its impact across key healthcare domains—such as acute and chronic disease management, cancer screening and care, mental health, and palliative care—is scarce. This study examines the pandemic’s impact on contacts, quality of care, and social disparity in these healthcare domains to guide better preparedness for future health emergencies.

Methods

The study utilized data from the Danish National Clinical Quality Registries, covering January 2015 to June 2022, to create a nationwide cohort for comparing healthcare metrics across the pandemic’s phases and the prepandemic period. Healthcare contacts were assessed through descriptive analyses, while the quality of care and social disparities were analysed using multivariable regression models, providing estimated prevalence ratios and 95% confidence intervals.

Results

The first wave of the COVID-19 pandemic in Denmark led to community and healthcare lockdowns, which were associated with fewer hospital contacts and reduced participation in national cancer screening programs. However, a gradual recovery towards prepandemic levels was found, with the exceptions of chronic obstructive pulmonary disease contacts and colorectal cancer incidence. Overall, the quality of care across various healthcare domains in Denmark remained largely unchanged or improved slightly during the pandemic. However, social disparities in contacts were increased across all examined healthcare domains, with patients who were immigrants, living alone, had limited educational level or low income experiencing reduced contact compared to the prepandemic period.

Conclusions

Overall, the Danish healthcare system appeared to be resilient and largely unaffected throughout the pandemic, and the quality of care in several healthcare domains remained high. Nevertheless, the increasing social disparities in healthcare contacts during the pandemic demands attention. In preparing for future health crises, it is important to address and mitigate potential social inequalities, focusing on achieving equity in healthcare.
Extracting Herbrand systems from refutation schemata
Authors: Leitsch Alexander , Lolic Anela
Published: February 2025

An inductive proof can be represented as a proof schema, i.e. as a parameterized sequence of proofs defined in a primitive recursive way. A corresponding cut-elimination method, called schematic cut-elimination by resolution, can be used to analyse these proofs, and to extract their (schematic) Herbrand sequents, even though Herbrand’s theorem in general does not hold for proofs with induction inferences. This work focuses on the most crucial part of the schematic cut-elimination method, which is to construct a refutation of a schematic formula that represents the cut-structure of the original proof schema. We develop a new framework for schematic substitutions and define a unification algorithm for resolution schemata. Moreover, we introduce a new calculus for the refutation of formula schemata that is simpler and more expressive than previous formalisms. Finally, we show that this new formalism allows the extraction of a structure from the refutation schema, called a Herbrand system, which represents its Herbrand sequent.
Phylogeography Analysis Reveals Rabies Epidemiology, Evolution, and Transmission in the Philippines
Authors: Zhang Liang , Cruz Jeffrey , Tian Yao , Wang Yuyang , Jiang Jianfeng , Gonzales Riva Marie , Azul Rachel R , Peña Rainelda C Dela , Sun Sheng , Liu Yan , Jiang Tao , Fang Liqun , Tu Changchun , Gong Wenjie , Feng Ye
Published: February 2025

Rabies, caused by rabies virus, is a severe public health problem in the Philippines, where animal rabies epidemiology had been extensively investigated, but little is known about the national epidemiologic situations since 2010. Here, we report a 12-year nationwide animal rabies surveillance with systematic phylogenetic analysis, in which 353 whole genomes of rabies viruses collected from animal rabies cases between 2018 and 2022 were obtained. The phylogenetic and spatial–temporal evolutionary analyses showed that rabies viruses in the Philippines were exclusively classified into the SEA4 subclade within the Asian clade, but forming three major geographically specific lineages. Intra-island spread predominates the rabies transmission in three major island regions, while the inter-island transmission, between major island regions, is very limited, likely due to ocean barriers. Overall, our findings have provided the most comprehensive dataset on the infected animal species, geographic distribution, transmission dynamics, genetic diversity of rabies viruses, and transmission risk factors, thus established a basis to support WOAH-endorsed national control program for dog-mediated rabies in the Philippines.
VEXAS syndrome through a rheumatologist’s lens: insights from a Spanish national cohort
Authors: García-Escudero Paula , López-Gómez Marta , López Berta Magallares , Dorta Alicia García , Frade-Sosa Beatriz , Lizarzaburu Meritxell Sallés , Rúa-Figueroa Íñigo , Fiallo Dolly Viviana , Toyos Sáenz de Miera Francisco Javier , Melero-Gonzalez Rafael Benito , Dios Santos Diego , Miranda José Alberto , Belando Clara García , Boselli Giuliano , Boteanu Alina Lucica , Villalobos Lourdes , Selaya Cristina Corrales , Sieiro Santos Cristiana , Álvarez Elvira Díez , Font Judit , Alonso Elena Riera , Araguás Ernesto Trallero , Merayo Eugenia Enríquez , Rodriguez-Laguna María , Monjo Irene , Gómez Ignacio Vázquez , Vela-Casasempere Paloma , Merino Carolina , Martínez Marta Ibáñez , Beriain José Ángel Hernández , Ruiz-Román Alberto , Calvo-Alén Jaime
Published: February 2025

Objectives

To describe the clinical spectrum of VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, and somatic) syndrome in patients managed by rheumatology units and analyse genotype–phenotype correlations.

Methods

A multicentre, cross-sectional, retrospective study was conducted across 126 Spanish hospitals. Patients with VEXAS syndrome diagnosed between December 2020 and January 2024 were included. Demographic data, clinical manifestations, laboratory findings, genetic analyses, treatments and outcomes were collected from medical records.

Results

Thirty-nine male patients were included (mean age at diagnosis: 72.78 years). Common manifestations were cutaneous lesions (87.18%), polyarthritis (82.05%) and fever (79.49%). Renal involvement was observed in 20.51% of patients. Genetic testing confirmed ubiquitin-like modifier-activating enzyme 1 mutations in all cases: 18 M41L, 14 M41T, 6 M41V and 1 novel mutation of unknown significance at site c.209T>A. The M41V mutation was significantly associated with renal involvement, while M41T was linked to deep vein thrombosis and thrombocytopaenia. Glucocorticoids were used in all patients, with improved response rates post-diagnosis (55.26% vs 97.14%) probably influenced by an increase in administered doses. IL-6 inhibitors and JAK inhibitors showed promising response rates (75% and 76.92%, respectively).

Conclusions

This study provides insights into the clinical spectrum of VEXAS syndrome in rheumatology settings, highlighting a higher prevalence of joint symptoms and renal involvement than previously reported. Genotype–phenotype correlations were observed, with M41V significantly associated with renal involvement and M41T linked to deep vein thrombosis and thrombocytopaenia. A new, presumably causative variant of VEXAS syndrome at site c.209T>A was described. These findings contribute to the growing understanding of VEXAS syndrome and may inform future diagnostic and treatment strategies.
Revisiting Board Independence Mandates: Evidence from Director Reclassifications
Authors: Bowen Donald E , Taillard Jérôme P
Published: February 2025

We provide causal evidence on the effects of mandated board independence. We compare firms that replace existing non-independent directors to firms that retain these directors by reclassifying them as independent. Reclassification eligibility, being largely predetermined, offers quasi-exogenous variation in compliance strategies. We show that firms required to replace insiders perform worse post-mandate, driven by increased operational costs and reduced labor efficiency. Boards of non-reclassifying firms retain fewer former employees and replace them with directors more likely to join monitoring-focused committees, emphasizing the shift from advising to monitoring. Overall, these findings suggest that firm-specific director expertise contributes materially to performance and is consistent with pre-mandate board compositions optimized to balance benefits of enhanced monitoring against costs of reduced advisory capacity. We rule out alternative explanations, including adjustment costs due to director turnover and co-option. Our study underscores the importance of allowing firms flexibility in governance structures and cautions against uniform mandates.
Self-settlement and the Challenges of Local Integration of Syrians in the Absence of Government Support
Authors: Karaoğlu Ezgi , Nawyn Stephanie J
Published: February 2025

Refugees’ opportunities for third-country resettlement have always been limited, but in recent years resettlement opportunities have become scarce. Syrians who sought protection in Türkiye initially expected to either return to Syria or be resettled within several years, but now acknowledge that they must remain in Türkiye. The Turkish government provides humanitarian assistance for registered Syrian refugees who need their basic needs met, but virtually no government programmes address the needs of middle-class Syrians. This article examines the experiences of middle-class Syrians in their efforts to establish settled lives in Istanbul now that resettlement programmes for Syrians in the country have ended. They navigated numerous daily and routine challenges related to identity, language acquisition, residential choices, and entitlement to citizenship. They did all this without support or guidance from formal government policies, pursuing one of two paths. One path involved becoming an expat, still foreign but more elite than a refugee. The other involved becoming “like a Turk” and included more engagement with the host community. These findings offer insights into the complex processes of belonging, visibility, and the interplay of identities within an urban context, and highlight the challenges refugees face when governments fail to support resettlement or local integration.
Application of Bacillus velezensis 160 for the biocontrol of Botrytis cinerea in pomegranate
Authors: Patricio-Hernandez Alberto , Quezada-Salinas Andrés Quezada-Salinas , Moreno-Velázquez Magnolia , Anducho-Reyes Miguel Angel , Mercado-Flores Yuridia
Published: February 2025

Botrytis cinerea is the causal agent of gray mold, a disease that attacks many plants worldwide. This phytosanitary problem was reported in orchards in the State of Mexico, Mexico, specifically in pomegranate crops. This study isolated this phytopathogen from fruits collected in the municipality of Chilcuautla, state of Hidalgo, Mexico, indicating that the disease is spreading across the country. Two strains of phytopathogens, MIC and MID, were obtained after conducting Koch’s postulates. These strains were identified molecularly by amplifying and analyzing the concatenated sequence of the regions that correspond to the internal transcript spacer (ITS), glyceraldehyde-3-phosphate dehydrogenase (G3PDH), and DNA-dependent RNA polymerase subunit II (RPB2). In vitro confrontation tests demonstrated that B. velezensis 160 inhibited the development of both strains of B. cinerea under study through the action of nonvolatile thermostable and volatile metabolites. Applying this bacteria to pomegranate orchards for two consecutive years (2022, 2023) decreased the incidence, severity, and progression of the disease. We conclude that this bacterium can be used as a fungicide to control gray mold in pomegranate crops.
Impact of DMI fungicides on Bacillus subtilis cell growth and consequences for disease control
Authors: Wesche Johanna , Schnabel Guido
Published: February 2025

Strategic mixtures of biological control agents (BCA) with demethylation inhibitor (DMI) fungicides to control diseases of fruit crops can result in additive interaction, synergism, or antagonism. To evaluate the compatibility of eight commercial DMI fungicides with the BCA Bacillus subtilis AFS032321, marketed as Theia, bacteria were cultured in nutrient broth with 0, 10, 50, 100, and 150 µg/ml of each DMI fungicide at 30°C on a shaker rotating at 180 rpm and the optical density (OD600) was measured after 24 and 48 h. In addition, nutrient agar (NA) was enriched with the same concentrations and an endospore suspension was streaked out to count colony-forming units (CFU/ml) and measure the colony diameter. Results showed vegetative cell growth was strongly inhibited at > equal to 50 µg/ml difenoconazole and > equal to 100 µg/ml tebuconazole. All other DMI fungicides had little impact on B. subtilis AFS032321 cell growth at any concentrations tested. Interestingly, mefentrifluconazole significantly promoted colony growth (diameter) at all concentrations on NA. Theia applied at label rate combined with vegetative growth-promoting DMI fungicide mefentrifluconazole (formulated as Cevya) or vegetative growth-suppressing DMI fungicide difenoconazole (formulated as Inspire) at 150 µg/ml a.i. (active ingredient) were investigated against gray mold of cherry. Disease incidence and severity 5 days after inoculation indicated the best control efficacy and synergism (+10.2) for the mixture Theia + Cevya. For the mixture Theia + Inspire an antagonistic effect (-6.8) was calculated. Our results indicate that compatibility between biological and conventional fungicides must be considered if they are used in mixtures or together in integrated spray programs.
Bleeding management of thoracic trauma
Authors: Werner Marie , Bergis Benjamin , Duranteau Jacques
Published: February 2025

Purpose of review

Thoracic injuries are directly responsible for 20–30% of deaths in severe trauma patients and represent one of the main regions involved in preventable or potentially preventable deaths. Controlling bleeding in thoracic trauma is a major challenge because intrathoracic hemorrhagic lesions can lead to hemodynamic instability and respiratory failure.

Recent findings

The aim of managing intrathoracic hemorrhagic lesions is to control bleeding as quickly as possible and to control any respiratory distress. Extended focus assessment with sonography for trauma enables us to identify intrathoracic bleeding much more quickly and to determine the most appropriate therapeutic strategy.

Thoracic bleeding can result from the diaphragm, intrathoracic vessels (aorta, but also inferior or superior vena cava, and suprahepatic veins), lung, cardiac, or chest wall injuries. Depending on thoracic lesions (such as hemothorax or hemopericardium), hemodynamic instability, and respiratory failure, a pericardial window approach, sternotomy, thoracotomy, or emergency resuscitation thoracotomy may be considered after discussion with the surgeon. Alongside treatment of injuries, managing oxygenation, ventilation, hemodynamic, and coagulopathy are essential for the patient’s outcome.
Nail Plafond Angle: A Novel Technique to Evaluate for Intraoperative Coronal Malalignment in Tibia Fractures
Authors: Jodoin Zachary , Koslosky Ezekial , Williamson Tyler , Karia Ravi , Hand Thomas
Published: February 2025

Objective:

Orthopedic management of distal tibia fractures presents a difficult challenge with high rates of malignment. Intramedullary nailing demonstrates coronal malalignment rates of 5% to 30%. This malignment has been associated with decreased satisfaction with outcomes. This stresses the importance of obtaining appropriate intraoperative nail alignment. This article helps address the rate of coronal plane malreduction during intramedullary nailing of distal tibial shaft fractures. This novel fluoroscopic technique analyzes the intraoperative angle between the distal end of the tibial nail and the tibial plafond [the nail plafond angle (NPA)].

Materials and Methods:

Retrospective review study of 100 subjects with distal tibia fractures at a single level 1 trauma center. Coronal nail alignment was measured on intraoperative fluoroscopic films utilizing the NPA. This measurement was then compared with full-length film alignment postoperatively analyzing for overall malreduction and correlation between the measurements. All measurements were completed by at least 2 orthopedic trained physicians.

Results:

Coronal alignment was compared, and there was a strong correlation between the measured varus and valgus angulation using the intraoperative technique and the full-length postoperative films (R = 0.74). The overall coronal malalignment while utilizing the NPA technique was 8% (8/100 patients).

Discussion:

The overall malalignment utilizing the NPA intraoperatively was 8%, which is substantially lower than the generally accepted literature malreduction rate of distal tibia fractures treated with intramedullary fixation. This novel technique could be added to the armamentarium of tools to assist in preventing the malreduction of distal tibia shaft fractures.
Blood pressure measurement at kiosks in public spaces: systematic review and consensus statement by the European Society of Hypertension Working Group on Blood Pressure Monitoring and Cardiovascular Variability endorsed by the International Society of Hypertension and the World Hypertension League
Authors: Stergiou George S. , Kyriakoulis Konstantinos G. , Kollias Anastasios , McManus Richard J. , Menti Ariadni , Parati Gianfranco , Schutte Aletta E. , Wang Jiguang , Asayama Kei , Asmar Roland , Bilo Grzegorz , Chapman Niamh , Fujiwara Takeshi , Head Geoffrey , Kahn Nadia , Kario Kazuomi , Li Yan , Manios Efstathios , Mariglis Dimitrios , Mihailidou Anastasia S. , Muntner Paul , Myers Martin , Niiranen Teemu , Ohkubo Takayoshi , Omboni Stefano , Protogerou Athanasios , Saladini Francesca , Sharman James , Shimbo Daichi , De La Sierra Alejandro , Palatini Paolo
Published: February 2025

Kiosk devices for unsupervised self-measurement of blood pressure (BP) are being used in public spaces and healthcare settings in several countries. This statement by the European Society of Hypertension (ESH) Working Group on BP Monitoring and Cardiovascular Variability provides a review of the published evidence on kiosk BP devices and consensus recommendations for their requirements and clinical use. A systematic literature search identified 54 relevant studies. Kiosk BP measurements appeared to be close to office BP [mean difference systolic 0.2 mmHg (95% confidence intervals −1.3 to 1.8); diastolic −0.4 mmHg (−3.5 to 2.7)], and higher than daytime ambulatory and home BP [mean difference 6.0 mmHg (1.6–10.4)/5.0 (2–8) and 8.1 mmHg (–2.6 to 18.9)/0.2 (−9.6 to 10.0), respectively]. Randomized or observational studies using kiosk BP measurements for hypertension screening or for assessing hypertension control were also included, as well as studies investigating users’ and healthcare professionals’ opinions, acceptability, and perspectives regarding kiosk BP measurements, and validation studies of kiosk BP devices. These studies had considerable heterogeneity in design, setting, methodology, measurement protocol, and sample size. Thus, at present, the clinical utility of kiosk BP measurements is uncertain. This ESH consensus statement acknowledges the potential of kiosk BP measurement as an emerging method for unsupervised self-measurement in the context of opportunistic screening for hypertension in apparently healthy people and the long-term monitoring of people with diagnosed hypertension. Requirements for the design, validation, function, and use of kiosk BP monitors are provided, together with the pending research questions on their optimal implementation in clinical practice.
Awakening the Spiritual Identity in Adolescents With Cancer
Authors: Alshakhshir Nadeen Sami , Hendricks-Ferguson Verna L. , Ward Earlise , Ersig Anne L. , Montgomery Kathleen E.
Published: February 2025

Background

Awakening the spiritual identity in adolescents with cancer is a phenomenon that has not been fully explored. Nevertheless, empirical research shows that spirituality is associated with positive health outcomes for adolescents with cancer. This finding indicates that awakening the spiritual identity can serve as a coping mechanism in health contexts.

Objective

In this study, we (1) describe the essential structure of the process of awakening the spiritual identity as experienced and perceived by adolescents with cancer and (2) explore factors that facilitate or hinder the process.

Methods

We used a qualitative empirical phenomenological approach to explore the process of awakening the spiritual identity of adolescents with cancer. Ten adolescents completed a graphing-timeline activity and participated in semistructured interviews. We analyzed the data with an adapted version of Colaizzi’s method.

Results

Regarding the process of awakening the spiritual identity, we identified 4 theme categories corresponding to 12 themes. The essential structure of the process is cyclical and ongoing: once a triggering moment initiates the awakening, adolescents navigate it through connectedness with the transcendent while drawing strength from preexisting spiritual foundations and family.

Conclusions

We reveal the essential structure of the process of awakening the spiritual identity among adolescents with cancer and highlight factors affecting the process.

Implications for Practice

Expanding our understanding of the phenomenon of awakening the spiritual identity among adolescents may support nurses in addressing and fostering adolescents’ use of spirituality as a coping mechanism during cancer treatment.
Breast Carcinomas Resembling Acinic Cell Carcinoma
Authors: Qin Fengxia , Li Jiazhen , Zheng Yi , Jiang Chengying , Jia Yumian , Sun Hui , Xue Huiqin , Wang Xiaozi , Wang Lu , Qian Xiaolong , Niu Yun , Wen Hannah Y. , Guo Xiaojing
Published: February 2025

Acinic cell carcinoma (AciCC) of the breast is an exceptionally rare subtype of invasive breast carcinoma, often exhibiting a triple-negative phenotype and relatively indolent behavior. Since the first case reported by Roncaroli and colleagues in 1996, no more than 60 additional cases have been described in English medical journals, usually as case reports or small case series. In this study, we presented an in-depth analysis of 14 cases of AciCC of the breast, including 4 pure AciCCs and 10 AciCCs mixed with other histologic types. We reported the clinicopathologic characteristics, histologic components, treatment modalities including response to neoadjuvant treatment in 3 patients, and outcomes. In addition, we assessed the expression of nuclear transcription factor nuclear receptor subfamily 4 group A member 3 by immunohistochemistry and gene rearrangements by fluorescence in situ hybridization, which has been implicated in AciCC of the salivary gland. All 14 cases were negative for nuclear receptor subfamily 4 group A member 3 expression, and no gene rearrangements were detected. We also conducted a thorough review of the literature to highlight advancements in understanding this rare breast cancer subtype. This study aims to enhance clinical knowledge of AciCC of the breast and contributed to growing evidence that AciCC of the breast and AciCC of the salivary glands appear to be unrelated entities, despite sharing a similar histologic appearance.
Impact of oral sensory function including proprioception on swallowing in patients with stroke
Authors: Park So-Hyun , Ham Dae-Hoon , Shin Joon-Ho
Published: February 2025

Objective

To assess oral sensory deficits and their correlation with mastication and swallowing in patients with stroke.

Design

This prospective observational study was conducted in the stroke unit of a rehabilitation hospital. The inclusion criterion was first occurrence of stroke with a unilateral lesion. Patients underwent oral sensory tests, including tactile sensation (light touch, two-point discrimination) and proprioception, along with mastication and swallowing assessments via videofluoroscopic swallowing study (VFSS) and Test of Masticating and Swallowing Solids (TOMASS).

Results

Among 36 patients, contralesional sides exhibited reduced oral sensory function (light touch, two-point discrimination, and proprioception of lips) compared with ipsilesional sides (p = 0.003, p = 0.001, p = 0.046, respectively). Oral proprioception was negatively correlated with mastication and swallowing. Proprioception of tongue showed negative correlation with mastication (p = 0.035), while combined value of proprioception of teeth, lip, and tongue showed negative correlation with time per swallow. Contralesional light touch and two-point discrimination influenced swallow items in TOMASS and pharyngeal phase items in VFSS.

Conclusion

Patients with stroke demonstrated contralesional oral sensory deficits, which were associated with impaired mastication and swallowing. Oral proprioception was correlated with mastication and swallowing, whereas tactile sensation correlated with the pharyngeal phase.
Comparative study of two common methods for the determination of total mercury in soil
Authors: Qin Pinzhu , Cai Ziyu , Wei Cuilan , Guan Ying , Li Bowen , Huang Jiali , Cheng Xiamin
Published: February 2025

Cold atomic absorption spectrophotometry and atomic fluorescence methods were employed to ascertain the total mercury concentration in soil samples. A systematic comparison and analysis were conducted on the operational procedures, precision and detection limits of these methodologies. The standard curve for total mercury determination in soil using the atomic fluorescence method is
y
= 851.98
x
+16.771 (
R
2
= 0.9996, 0–2.5 µg l
−1
), with a detection limit of 0.0006 mg kg
−1
. This method demonstrates superior precision and accuracy not only for samples with high and medium concentrations but also for those with low concentrations. For the cold atomic absorption spectrophotometry method, the standard curve for total mercury determination is
y
= 0.0547
x
+ 0.0047 (
R
2
= 0.9998, 0–15 µg l
−1
). For high-concentration samples, the curve is
y
= 0.0007
x
− 0.0003 (
R
2
= 0.9998, 0–600 µg l
−1
). The detection limit for this method is 0.06 μg kg
−1
, indicating better sensitivity and accuracy compared with the atomic fluorescence method. While the precision for low-concentration (0.017 ± 0.003 mg kg
−1
) samples is moderate, it is higher for medium (0.030 ± 0.003 mg kg
−1
) and high-concentration (0.590 ± 0.05 mg kg
−1
) samples. Overall, there is no significant difference between the two detection methods. However, the cold atomic absorption spectrophotometry method has the advantage of not requiring pre-treatment, making it more convenient and environment friendly.
Kinetic Monte Carlo methods for three-dimensional diffusive capture problems in exterior domains
Authors: Bernoff Andrew J. , Lindsay Alan E.
Published: February 2025

Cellular scale decision-making is modulated by the dynamics of signalling molecules and their diffusive trajectories from a source to small absorbing sites on the cellular surface. Diffusive capture problems which model this process are computationally challenging due to their complex geometry and mixed boundary conditions together with intrinsically long transients that occur before a particle is captured. This paper reports on a particle-based kinetic Monte Carlo (KMC) method that provides rapid accurate simulation of arrival statistics for (i) a half-space bounded by a surface with a finite collection of absorbing traps and (ii) the domain exterior to a convex cell, again with absorbing traps. We validate our method by replicating classical results and verifying some newly developed boundary homogenization theories and matched asymptotic expansions on capture rates. In the case of non-spherical domains, we describe a new shielding effect in which geometry can play a role in sharpening cellular estimates on the directionality of diffusive sources.
Host traits and temperature predict biogeographical variation in seagrass disease prevalence
Authors: Schenck F. R. , Baum J. K. , Boyer K. E. , Duffy J. E. , Fodrie F. J. , Gaeckle J. , Hanley T. C. , Hereu C. M. , Hovel K. A. , Jorgensen P. , Martin D. L. , O’Connor N. E. , Peterson B. J. , Stachowicz J. J. , Hughes A. R.
Published: February 2025

Diseases are ubiquitous in natural systems, with broad effects across populations, communities and ecosystems. However, the drivers of many diseases remain poorly understood, particularly in marine environments, inhibiting effective conservation and management measures. We examined biogeographical patterns of infection in the foundational seagrass
Zostera marina
by the parasitic protist
Labyrinthula zosterae
, the causative agent of seagrass wasting disease, across >20° of latitude in two ocean basins. We then identified and characterized relationships among wasting disease prevalence and a suite of host traits and environmental variables. Host characteristics and transmission dynamics explained most of the variance in prevalence across our survey, yet the particular host traits underlying these relationships varied between oceans, with host size and nitrogen content important in the Pacific and host size and density most important in the Atlantic. Temperature was also a key predictor of prevalence, particularly in the Pacific Ocean. The strength and shape of the relationships between prevalence and some predictors differed in our large-scale survey versus previous experimental and site-specific work. These results show that both host characteristics and environment influence host–parasite interactions, and that some such effects scale up predictably, whereas others appear to depend on regional or local context.
Measuring adult mortality from mobile phone surveys in Burkina Faso, Malawi and the Democratic Republic of the Congo
Authors: Dianou Kassoum , Masquelier Bruno , Luhar Shammi , Lankoandé Bruno , Oren Ashira Menashe , Soura Abdramane , Bassinga Hervé , Tlhajoane Malebogo , Dulani Boniface , Akilimali Pierre , Reniers Georges
Published: February 2025

In many low and middle-income countries, adult mortality estimates are derived from surveys and censuses conducted through face-to-face interviews. These interviews can be time-intensive and are often impractical during health crises or humanitarian emergencies. The expansion in cellphone ownership and network coverage has created new opportunities for collecting demographic data through mobile phone surveys, but our understanding of selection biases and reporting errors of such data remains incomplete. This study reports on adult mortality estimates obtained through mobile phone surveys conducted in Burkina Faso, Malawi, and the Democratic Republic of the Congo in 2021 and 2022. To mitigate respondent fatigue and network interruptions, we used a shortened version of the set of questions generally used in surveys to ask about the survival of respondents’ siblings. We found substantial differences between mortality estimates obtained from mobile phone interviews and those from face-to-face demographic surveys. Mortality rates from the mobile phone surveys were also approximately half those expected from United Nations estimates. We attribute this underestimation to inaccuracies in reporting of ages and the timing of sibling deaths in the shortened sibling instrument. After imputing ages and dates based on full sibling histories collected in previous face-to-face surveys, mortality rates were more consistent with other data sources. Mobile phone surveys are promising for the measurement of adult mortality in settings where face-to-face surveys are hindered, but they are susceptible to reporting errors. More research is needed on the best set of questions to use for capturing recent adult deaths.
Exploration of the Social Determinants of Diarrhoea, Rotavirus Vaccine Uptake, and Vaccine ‘Fatigue’ in Ethiopia, Kenya, and Malawi
Authors: Phiri Mackwellings , Osman Rahma , Weldegebriel Shewit , Sabola Steven , Ongadi Beatrice , Beavis Catherine , Mwendera Chikondi , Nyirenda Deborah ,   GHRG-GI Consortium
Published: February 2025

Diarrhoea due to rotavirus remains a significant cause of child mortality in developing regions. Caregivers’ perspectives on the social determinants of gastroenteritis and childhood vaccination, including the rotavirus vaccine, were explored through focus group discussions in Ethiopia (n=6), Kenya (n=14), and Malawi (n=10), using a combination of thematic and framework analysis approaches. The results show that diarrhoea was perceived to be a burden in all three countries, particularly among infants, due to challenges in WASH (water, sanitation, and hygiene) infrastructures and poverty. Prevention strategies mentioned by the caregivers focussed on enhancing WASH interventions without mention of vaccination. Participants however expressed a lack of agency to address WASH at community level in informal settlements where the studies were conducted. Antibiotics were seen as “strong medications” and often purchased without prescription for treatment of diarrhoea, raising concerns on Anti-Microbial Resistance (AMR), while home remedies such as rice porridge were used for less severe diarrhoea symptoms. Perceived or experiential benefits and safety of previous vaccines promoted vaccine uptake in all three countries. On the other hand, limited understanding of vaccines, concerns about side effects, perceived excessive vaccination, mistrust of vaccines or suspicions of existing vaccines undermined individuals’ willingness to vaccinate children. Our results highlight that a lack of attention to socio-determinants of poor health in contexts where there are several vaccines and yet a high incidence of vaccine-preventable diseases may undermine vaccine confidence. Multi-sectoral interventions to tackle social determinants of diarrhoea and improve community understanding of vaccines are required to improve overall community health outcomes.
Data-Driven Insights on Opioid Use and Health Behavior Trends Following Decriminalization: Zero-Shot Sentiment and Behavior Analysis
Authors: Moridani Sepehr Harfi , Yang Chan Pang , Noaeen Mohammad , Shakeri Zahra
Published: February 2025

Opioid decriminalization has taken on renewed urgency in regions grappling with high mortality and health-care costs. Traditional assessments often focus on legal or epidemiological data, leaving gaps in understanding how the public actually perceives and reacts to such policies. This paper introduces an AI-driven approach that applies Mistral, a Large Language Model (LLM), to a corpus of over 22,000 Reddit comments discussing British Columbia’s decriminalization policy. Our method uses zero-shot classification to track shifts in sentiment and self-reported behaviors related to opioid use and harm reduction. The findings suggest that online conversations initially reflected optimism about reduced stigma and broader acceptance of harm reduction measures, but sentiment became more mixed as policy details and lived experiences surfaced. This pattern indicates that advanced LLM-based text analysis can yield deep insights into the evolving public narrative on health interventions, informing future policymaking and healthcare strategies.
TOPOLOW: A MAPPING ALGORITHM FOR ANTIGENIC CROSS-REACTIVITY AND BINDING AFFINITY ASSAY RESULTS
Authors: Arhami Omid , Rohani Pejman
Published: February 2025

Motivation: Understanding antigenic evolution through cross-reactivity assays is crucial for tracking viral pathogens and informing vaccine development, particularly for rapidly evolving pathogens requiring regular vaccine updates. However, existing cartography methods, commonly based on multidimensional scaling (MDS), face significant challenges with sparse data, producing incomplete and inconsistent maps. There is an urgent need for robust computational methods that can accurately map antigenic relationships from incomplete experimental data while maintaining biological relevance, especially given that up to 95% of possible measurements may be missing in large-scale studies. Results: We present Topolow, a physics-inspired optimization framework that transforms cross-reactivity and binding affinity measurements into accurate positions in a phenotype space. By modeling antigenic relationships as a system of particles connected by springs representing measured similarities, with selective repulsion between unmeasured pairs, Topolow achieves superior performance compared to MDS. Applied to neutralization data for H3N2 influenza and HIV viruses, our method demonstrated 12% and 43% improvement in prediction accuracy respectively, while maintaining complete positioning of all antigens. Topolow determines optimal dimensionality through likelihood-based estimation, avoiding distortions due to insufficient dimensions, and demonstrates orders of magnitude better stability across multiple runs. The method effectively reduces experimental noise and bias, revealing the underlying antigenic relationships and clusters. Availability and implementation: Topolow is implemented in R and freely available at [https://github.com/omid arhami/topolow]. The package is optimized for both single machines and SLURM clusters, with parallel processing support for computational efficiency.
Leveraging Deep Learning to Enhance MRI for Brain Disorders
Authors: Dai Yuxiang , Yakupov Renat , Xia Yunman , Tang Wei , Lett Tristram , Nees Frauke , Polemiti Elli , Roy Jean-Charles , Chu Ying-Hua , Vaidya Nilakshi , Wang Chengyan , Chang Xiao , Xie Chao , Zhang Boyu , Zhao Xingzhong , Zheng Rencheng , Zheng Liping , Xu Shuai , King Sinead , Zhang Yuning , Zhang Zuo , Bokde Arun , Stringaris Argyris , ORFANOS Dimitri Papadopoulos , Barker Gareth J , Lemaitre Herve , Kebir Hedi , Walter Henrik , Sinclair Julia , Bruehl Ruediger , Whelan Robert , Schmidt Ulrike , Feng Jianfeng , Desrivieres Sylvane , Jia Tianye , Duezel Emrah , Marquand Andre , Wang He , Schumann Gunter
Published: February 2025

The limited availability and high cost of 7 Tesla (7T) structural MRI hinder its widespread application despite its superior imaging quality. This study introduces a High Frequency-Generative Adversarial Network (HF-GAN) to predict three-dimensional 7T-equivalent (P7T) images from standard 3T structural MRI scans, offering a cost-effective alternative. HF-GAN was trained on paired 3T and 7T MRI data and validated on external datasets, including STRATIFY/ESTRA (N=671) and ADNI2 (N=643), covering psychiatric and neurodegenerative disorders. Results indicate that P7T images generally exhibit enhanced contrast and better preservation of fine structural details compared to 3T, with improved sensitivity in detecting disease-related differences in key brain regions such as the thalamus, caudate, putamen, and frontal cortical areas. The partial η^2 values revealed that P7T explained a higher proportion of variance compared to 3T in most comparisons, highlighting its improved sensitivity to disease-related structural changes. These findings demonstrate that HF-GAN effectively enhances 3T MRI data quality, providing a scalable solution for research and clinical applications in neurodegenerative and psychiatric disorders. Additional validations in brain and other organ systems are warranted to further advance clinical translation.
Leveraging Large-Scale Biobanks for Therapeutic Target Discovery
Authors: Ferolito Brian R , Dashti Hesam , Giambartolomei Claudia , Peloso Gina M , Golden Daniel J , Gravel-Pucillo Kai , Rasooly Danielle , Horimoto Andrea RVR , Matty Rachael , Gaziano Liam , Liu Yi , Smit Ines A , Zdrazil Barbara , Tsepilov Yakov , Costa Lauren , Kosik Nicole , Huffman Jennifer E , Tartaglia Gian Gaetano , Bini Giorgio , Proietti Gabriele , Ioannidis Harris , Hunter Fiona , Hemani Gibran , Butterworth Adam S , Di Angelantonio Emanuele , Langenberg Claudia , Ghoussaini Maya , Leach Andrew R , Liao Katherine P , Damrauer Scott , Selva Luis E , Whitbourne Stacey , Tsao Philip S , Moser Jennifer , Gaunt Tom , Cai Tianxi , Whittaker John C , Program Million Veteran , Casas Juan P , Muralidhar Sumitra , Gaziano J Michael , Cho Kelly , Pereira Alexandre C
Published: February 2025

Large biobanks, including the Million Veteran Program (MVP), the UK Biobank, and FinnGen, provide genetic association results for more than 1,000,000 individuals for hundreds of phenotypes. To select targets for pharmaceutical development, as well as to improve the understanding of existing targets, we harmonized these studies, and performed two-sample Mendelian Randomization (MR) on 2,003 phenotypes using genetic variants associated with gene expression (derived from GTEx and eQTLGen) and plasma protein levels (derived from ARIC, Fenland, and DeCODE) as proxies of target modulation. We found 69,669 gene-trait pairs with evidence (p ≤ 1.6 x 10-9) for causal effects. From the selected gene-trait pairs, we observed 6,447 genes with strong causal evidence for at least one of 2,003 investigated traits. As expected, being identified as a gene-trait pair in our approach was significantly associated with higher odds of being an approved drug target and indication. We were able to rediscover 9% of approved drug targets in ChEMBL 34. Moreover, identified gene-traits were significantly associated with higher odds of being previously described as a gene-trait pair in OMIM, ClinVar, mouse knock-out data, and rare variant burden studies. To enhance the translational potential of the resource, we developed a predictive ranking model trained using approved drug targets described in ChEMBL 34 as well as several different biological annotations. This model was able to accurately predict the odds of a particular significant MR result being developed into an approved drug and its clinical indication (precision-recall AUC 0.79). We make our results publicly available inCIPHER.
Use of evidence-based cardiovascular preventive therapies in type 2 diabetes patients with established or high risk of atherosclerotic cardiovascular disease in China: A retrospective cohort study
Authors: Tian Jian-Qing , Lin yuhao , Zhang Zhi-Jun , Peng Yi-Ting , Ye Jia-Wen , Wang Zhi-Yi
Published: February 2025

Aims To examine trends of glucose-, blood pressure-, and lipid-lowering drugs and antiplatelet medications with cardiovascular benefit in type 2 diabetes (T2DM) patients with established or high risk of atherosclerotic cardiovascular disease (ASCVD). Materials and methods In this retrospective cohort study, we identified T2DM patients with established or high risk of ASCVD using diagnostic codes from the institutional data of Xiamen Humanity Hospital between 2018 and 2023. The prescription of any of the glucagon-like peptide-1 receptor agonist (GLP-1 RA) or sodium glucose cotransporter-2 inhibitors (SGLT2i), angiotensin-converting enzyme inhibitors (ACEI) or angiotensin-receptor blockers (ARB), moderate-intensity statins, and aspirin was quantified using frequencies/percentages. Results We identified 17,320 patients with T2DM and established or high risk of ASCVD, with a mean of 66.3 years and 43.9% of patients were women. From 2018 to 2023, the use of GLP-1 RA increased from 2.7% to 13.7%; SGLT2i increased from 3.9% to 16.5%; ACEI/ARB increased from 28.1% to 43.0%; moderate-intensity statins increased from 61.6% to 70.5%; and aspirin increased from 23.7% to 32.9%. Overall, only 4.8% of patients were prescribed 4 evidence-based cardiovascular preventive therapies, and 17.6% of patients were not prescribed any of these medications. Conclusions This study demonstrated that despite a modest annual increase in the use of evidence-based cardiovascular preventive medications among patients with T2DM and established or high risk of ASCVD, less than 1 in 20 patients received all 4 medications. To maximize the potential population benefit of these therapies, further efforts are necessary on many fronts.
Large language model-assisted causal machine learning for identifying fatigue-related poor glycated hemoglobin in type 2 diabetes
Authors: Sufriyana Herdiantri , Romadlon Debby Syahru , Kurniawan Rudy , Al Baqi Safiruddin , Ekpor Emmanuel , Osei Eric Peprah , Chiu Hsiao-Yean , Su Emily Chia-Yu
Published: February 2025

Background

Fatigue is common but mostly untreated in type 2 diabetes, since it requires a diagnostic workup which is hardly justified by fatigue alone. Individually identifying fatigue-related cause help decide effective follow-up and prioritize resource utilization. This study aimed to determine whether glycated hemoglobin (HbA1c) level contributes to fatigue for each individual case using a fatigue prediction model based on large language model (LLM)-assisted structural causal modeling (SCM).

Methods

Retrospective cohort design was applied to collect data from diabetes management centers in Indonesia. We conducted SCM to select predictors among HbA1c and other variables for fatigue predictive modeling. Causal diagram was constructed by inferring the causal direction for each pair of correlated variables via LLM, i.e., GPT-4. The models were trained using eight machine learning (ML) algorithms. The best one was selected among the models that fulfilled sufficient sample size, was well-calibrated, and had positive net benefit using threshold closest to 95% specificity in our data. We chose the best model based on the area under curve (AUC) of receiver operating characteristics (ROC) and the concordance between the feature impact on model output based on the beeswarm plot of the Shapley additive explanation (SHAP) values and the effect size based on SCM. The SHAP waterfall plot was utilized to quantify HbA1c contribution to fatigue for each individual case.

Results

Individuals with type 2 diabetes receiving OHA last 3 months (n=281) were more likely to report fatigue when they had poor HbA1c (adjusted odds ratio [aOR]=6.1, 95% CI 2.5, 14.4), comorbidity (aOR=25.2, 95% CI 12.1, 52.4), or a need for insulin treatment (aOR=3.6, 95% CI 2.0, 6.4). The best model used random forest algorithm (AUC-ROC=0.966, 95% CI 0.962, 0.969). Fatigue-related poor HbA1c could be individually identified among 95.1% (95% CI 94.5, 95.7) of those who reported fatigue.

Conclusions

We have developed a web application and nomogram for identifying fatigue-related poor HbA1c for each individual case. Future studies are warranted for external validation and randomized trials to examined the validity and impact of the cause identifier of fatigue in this study.