bluuebunny/crossref_metadata_2025 huggingface dataset:
Assessing the impact of macroeconomic and environmental concerns on Bitcoin in lower-income countries
Authors: Santiyano B J , Tanty V F , Hariwinarta J , Havidz S A H
Published: January 2025

This study investigated the effects of macroeconomic and environmental factors on Bitcoin return. The analysis included 31 lower-income countries selected based on their GDP rankings from 2012 to 2022. Using 341 observations, we applied Feasible Generalized Least Squares (FGLS) and One-step System Generalized Method of Moments (GMM) to evaluate the effects of Gross Domestic Product (GDP), Inflation Rate (INF), CO2 Emissions (CO2E), Climate Policy Uncertainty (CPU), Global Price Energy Index (GPEI), and Cambridge Bitcoin Electricity Consumption Index (CBECI) on Bitcoin return. The findings revealed a significant negative relationship between CO2E and Bitcoin return, reflecting investor concerns about Bitcoin’s environmental impact. CBECI showed a significant positive effect, suggesting that higher electricity consumption associated with mining activities led to increased Bitcoin return. CPU was positively associated with Bitcoin return, indicating that investors might have viewed Bitcoin as a hedge against climate policy uncertainties. GPEI had a significant negative effect, demonstrating Bitcoin’s sensitivity to global energy price fluctuations. GDP and INF showed no significant effect on Bitcoin return, suggesting that macroeconomic indicators did not significantly impact Bitcoin’s value in emerging markets. These results offered essential guidance for investors and policymakers in emerging markets.
Optimization of leading sectors and regional independence in the arek region, east java
Authors: Abdillah K , Edi A S , Aminatuzzuhro
Published: January 2025

Regional economic development focused on individual activities and analyzed the potential of regional income in diverse areas to formulate policies that encouraged faster economic growth. This study aimed to determine how economic potential and the degree of regional independence affected the economy in the Arek Region of East Java Province. A quantitative descriptive approach was used, employing secondary data from Statistics of East Java Province (BPS) with analyses of Location Quotient (LQ), degree of fiscal decentralization, and fiscal capacity index. The study concluded that there were 79 leading sectors, with Batu City having the highest average LQ of 12.10 in other service activities. The degree of fiscal decentralization indicated that 7 regions were classified as having deficient financial capacity, while 3 regions were classified as having low financial capacity. One region classified as having medium financial capacity was Surabaya City, with a score of 0.61. The fiscal capacity index calculation results revealed that 5 regions were classified as having very high fiscal capacity, 1 region as having high fiscal capacity, 3 regions as having medium fiscal capacity, and 2 regions with low fiscal capacity levels. Surabaya City had the highest fiscal capacity index at 6.65. Regions with leading sectors had the potential to improve the regional economy and increase regional independence through taxes generated from the currently developing business sector.
Financial satisfaction and financial management behavior: analysis of MSME’s coastal tourism sector
Authors: Gitayuda M B S , Purnamawati
Published: January 2025

This research sought to examine the effect of financial management practices on the financial satisfaction of MSMEs engaged in coastal tourism and to determine the determinants of financial satisfaction among these enterprises. A quantitative research approach was employed, utilizing descriptive and associative methods to illustrate the relationships between the studied variables. The sample consisted of 60 respondents representing MSMEs in Madura’s coastal tourism areas, specifically in the Pamekasan and Sumenep regencies. The independent variables comprised Financial Literacy and Financial Attitude, whilst the intervening variable was financial management behavior, with financial pleasure serving as the dependent variable. This quantitative descriptive study utilized a Likert scale to assess responses and adopted purposive sampling as its non-probability sampling technique. The analysis of data was performed via Structural Equation Modeling (SEM) and processed via SmartPLS 3.0 software. The results of the investigation were as follows: The relationship between Financial Literacy and Financial Management Behavior is positive; however, it does not have a direct impact on Financial Satisfaction. The financial attitude has a positive impact on both financial management behavior and financial satisfaction. Moreover, the behavior associated with financial management has a positive influence on financial satisfaction and serves as a mediator in the relationship between financial literacy and financial satisfaction, in addition to the relationship between financial attitude and financial satisfaction.
The influence of e-government integration and data interoperability policies on poverty reduction
Authors: Sarofah R , Ramdhani H , Firmadi S
Published: January 2025

This research analyzed the influence of e-government integration policies and data interoperability on poverty alleviation in Tasikmalaya City. The research was motivated by the importance of creating sustainable government governance, especially in realizing reduced poverty rates in Tasikmalaya City. One of the most appropriate approaches was service integration policy intervention. The research used a quantitative approach with survey research through data collection in questionnaires to 330 respondents using random sampling clusters spread throughout the sub-districts of Tasikmalaya City. The independent variables used were e-government policy and data interoperability. Apart from that, the dependent variable was poverty reduction. The data interoperability and e-government influenced poverty alleviation by 54.07%. On the other hand, some evidence suggested a connection between data interoperability and poverty reduction to a certain extent. This emphasized the importance of integration between agencies, which could be accessed through a collection of inter-agency activity programs, especially in the distribution of poverty assistance programs. Therefore, the Tasikmalaya City Government needed to immediately implement a data interoperability policy as a valuable effort to design economic empowerment programs and create an integrated public service online portal that provided information ranging from social assistance to workforce training programs. This service would make it easier for poor target groups to obtain accurate information as part of poverty reduction services. Some programs run by the Tasikmalaya City Government included distributing aid programs to the poor, providing information on job opportunities, and increasing information on various departmental collaboration programs.
Synergizing bioprinting and 3D cell culture to enhance tissue formation in printed synthetic constructs
Authors: Günther Daniel , Bergerbit Cédric , Marsee Ary , Vedaraman Sitara , Pueyo Moliner Alba , Bastard Céline , Eelen Guy , Gerardo Nava José Luis , Dewerchin Mieke , Carmeliet Peter , Kramann Rafael , Schneeberger Kerstin , Spee Bart , De Laporte Laura
Published: January 2025

Bioprinting is currently the most promising method to biofabricate complex tissues in vitro with the potential to transform the future of organ transplantation and drug discovery. Efforts to create such tissues are, however, almost exclusively based on animal-derived materials, such as gelatin methacryloyl, which have demonstrated efficacy in bioprinting of complex tissues. While these materials are already used in clinical applications, uncertainty about their safety still remains due to their animal origin. Alternatively, synthetic bioinks have been developed that match the printability of natural bioinks but lack their biological complexity, and thereby often fail to support cell growth and facilitate tissue formation. Additionally, most synthetic materials do not meet the mechanical demands of bioprint stable constructs while providing a suitable environment for cells to grow, limiting the number of available bioinks. To bridge this gap and synergize bioprinting and 3D cell culture, we developed a polyethylene glycol-based bioink system to promote the growth and spreading of cell spheroids that consist of human primary endothelial cells and fibroblasts. The 3D bioprinted centimeter-scale constructs have a high shape fidelity and accelerated softening to provide sufficient space for cells to grow. Adjusting the rate of degradability, induced by the integration of ester-functionalized crosslinkers in addition to protease cleavable crosslinkers into the hydrogel network, improves the growth of spheroids in larger printed hydrogel constructs containing an interconnected channel structure. The perfusable constructs enable extensive spheroid sprouting and the formation of a cellular network upon fusion of sprouts as initial steps toward tissue formation with the potential for clinical translation.
Study on the mechanical behavior of corroded bridge steel based on the entire process of tensile failure
Authors: Li Yi , Hu Dapeng , Xu Yangming , Wang Bo , Zhou Yongjun , Dong Zhonghong
Published: January 2025

The Q345qD bridge steels exposed to severe corrosion environments undergo mechanical property degradation, posing significant safety risks for sea-crossing bridges. Assessing the health of corroded bridge steel structures under load conditions in a manner that avoids causing damage can effectively prevent these intensifying safety hazards. To investigate the impact of corrosion on the mechanical performance of these steels, six sets of standard specimens underwent corrosion ranging from 0 to 896 h. Subsequently, during tensile testing, an image acquisition platform was established to utilize Digital Image Correlation (DIC) techniques for capturing and observing the tensile loading processes of various corroded specimens. Analysis of stress–strain curves and strain field evolution patterns provided insights into the deterioration of mechanical properties of Q345qD bridge steels after corrosion. For corroded bridge steel structures, defects caused by the corrosion pits can still result in localized strain concentration under low load levels. At higher load levels, mass loss due to corrosion or reduced cross-sectional dimensions of load-bearing elements are the primary causes of mechanical performance decline, precipitating overall structural failure. These findings provide some references for routine maintenance of steel structures of cross-sea bridges.
Primes in Arithmetic Progressions to Large Moduli II: Well-Factorable Estimates
Authors: Maynard James
Published: January 2025

We establish new mean value theorems for primes of size

x
x

in arithmetic progressions to moduli as large as

x

3

/

5
−
ϵ

x^{3/5-\epsilon }

when summed with suitably well-factorable weights. This extends well-known work of Bombieri, Friedlander and Iwaniec, who handled moduli of size at most

x

4

/

7
−
ϵ

x^{4/7-\epsilon }

. This has consequences for the level of distribution for sieve weights coming from the linear sieve.
Cross-sectional survey of healthcare professionals’ perceptions of bedrails as a measure of physical restraint in the hospital setting
Authors: Gálvez-Barrón César , González-De Luna Ana , Pérez-López Carlos , Macho-Perez Oscar
Published: January 2025

Objective

Although bedrails are considered a restraint measure under the legal regulations in Spain, no data on the related perceptions of healthcare professionals (HCPs) are available. Thus, this study aimed to calculate the proportion of HCPs in the hospital setting that consider bedrails to be a restraint measure.

Methods

Between June and December 2022, a cross-sectional online survey was conducted among the HCPs at our institution. Basal information was collected in the first section, and seven questions related to bedrails were included in the second. The perception of bedrails as a restraint measure was evaluated with a multiple-choice question in which devices that can be considered restraint measures were listed.

Results

A total of 246 HCPs participated in the survey, 201 of whom passed quality control and were analysed. The mean age was 42.2 years old, and 85% of the participants were women.

The proportion of HCPs who considered bedrails as a restraint measure was 54.2% (95% confidence interval [CI]: 47.3–61.1) in the total group and 54.5% (95% CI: 44.1–65.0) in the intermediate care subgroup. These proportions were significantly lower for HCPs who worked night shifts and among those who believed that bedrails do not limit patient mobility.

Conclusions

There is a considerable difference between what is established in legal regulations and the perceptions of HCPs in terms of bedrails being considered a restraint measure. Our results can help improve the content of training programs on the use of restraint measures by HCPs.
Association between wine consumption and migraine: a systematic review and meta-analysis of cross-sectional
Authors: Lucerón-Lucas-Torres Maribel , Ruiz-Grao Marta C , Pascual-Morena Carlos , Priego-Jiménez Susana , López-González María , Álvarez-Bueno Celia
Published: January 2025

Background

It seems that diet is one of the main triggers of migraine; one of the most studied is alcohol, and also, over the years, red wine has been shown to trigger headaches. Therefore, this systematic review and meta-analysis aims to examine the strength of the association between wine consumption and migraine.

Methods

In this systematic review and meta-analysis, a search of MEDLINE (via PubMed), Scopus, Cochrane, and Web of Science databases was conducted to assess the association between wine consumption and migraine, covering baseline to December 2023. Pooled Odds Ratio (p-OR) were calculated using the DerSimonian and Laird methods. This study was previously registered in PROSPERO (CRD42024511115). The risk of bias was evaluated using The Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies.

Results

Five studies were included in this systematic review, and only four of them were in the meta-analysis. Using the DerSimonian and Laird method, the p-OR for the effect of wine consumption on migraine was 0.63 (95% CI 0.36–1.09). The included studies after the risk of bias assessment showed a moderate risk of bias.

Conclusions

The findings of this systematic review and meta-analysis indicate that there is no conclusive evidence to support an increased or decreased risk of migraine associated with wine consumption.
Overview of historical occupational exposure to trichloroethylene in China
Authors: Nie Jia , Ge Calvin B , Rothman Nathaniel , Hu Wei , Vermeulen Roel , Lan Qing , Peters Susan
Published: January 2025

Objectives

Trichloroethylene (TCE) is a carcinogen that has been causally linked to kidney cancer and possibly other cancer sites including the liver and lymphatic system. Its use in China has increased since the early 1990s due to the growing metal and electronic industries. We aimed to summarize the major sources of occupational exposure to TCE over time in China.

Methods

Occupational TCE exposure assessments were extracted from both the Chinese and English scientific literature, as well as from industrial hygiene surveys performed in Guangdong, Tianjin, and Hong Kong. Weighted mean concentrations were summarized by occupation and industry.

Results

We extracted over 12,412 measurements from 55 industries and 35 occupations across China since 1976, of which at least 201 were from case reports. More than half of the measurements were derived from 4 industries, including “manufacture of footwear” (29%), “manufacture of electronic components and boards” (17%), “manufacture of games and toys” (14%), and “manufacture of fabricated metal products, except machinery and equipment” (13%). Several occupations, including “electronic-equipment assemblers,” “metal-, rubber-, and plastic-products assemblers,” “metal finishing-, plating-, and coating-machine operators,” “precision-instrument makers and repairers,” “printing-machine operators,” and “ore and metal furnace operators” were identified as having high risks of TCE exposure, with either pooled weighted mean task-based or full-shift concentrations over 150 mg/m3 over the years. TCE exposure levels varied across different occupations and changed over time. In 1990 and earlier, 1991 to 2000, the exposure levels were at their highest with pooled weighted mean task-based concentrations of 202.8 and 242.9 mg/m3, respectively. Subsequently, the level decreased to 118.7 mg/m3 from 2001 to 2010 before increasing again to 216.0 mg/m3 from 2011 onwards. This overall trend was also observed for “electronic-equipment assemblers” and “metal finishing-, plating-, and coating-machine operators.” However, for “precision-instrument makers and repairers,” the exposure levels consistently declined over the years.

Conclusions

Over the past few decades, degreasing-related occupations, such as “electronic-equipment assemblers” and “metal finishing-, plating-, and coating-machine operators” have been consistently identified as being at high risk of significant TCE exposure and continued to warrant attention. Identifying high-risk industries and occupations can inform the development of targeted interventions and regulations to mitigate TCE exposure. Furthermore, enhancing the quality and coverage of exposure measurement data in occupational settings will advance epidemiological investigations in occupational health.
Daily noise dose and power tool characterization of steel stud framers on commercial construction sites
Authors: Schutt David , Lipsey Tiffany , Van Dyke Mike , Brazile William J
Published: January 2025

The construction industry is well-documented as having numerous sources of hazardous noise on the job. Framers who cut and install steel studs on commercial construction sites use a variety of power tools throughout the course of their normal workday and have the potential to be exposed to levels of noise that can lead to occupational noise-induced hearing loss. This study assessed the noise dose of commercial steel stud framers and characterized the noise of common power tools that contribute to their daily noise dose. Occupational exposure limits exist in both required and recommended forms to protect workers; however, large differences in the level of worker protection are apparent between the mandated Occupational Safety and Health Administration (OSHA) permissible exposure limit (PEL) and the voluntary National Institute for Occupational Safety and Health (NIOSH) recommended exposure limit (REL) for noise exposure. Steel stud framers in this study had a mean OSHA PEL dose of 27.6% and a mean NIOSH REL dose of 340.7% for the same workers. As a comparison, ambient equivalent noise doses at the construction site were 1.4% for PEL criteria and 12.4% for REL criteria. Of task assignments during the workday, workers who were assigned primarily as saw operators had statistically significant higher noise exposures than workers who were assigned as stud installers (P = 0.037). Octave band analysis was conducted for full-day exposures and indicated an upward trend of higher noise exposures at higher frequencies. Overall, among all steel stud framers involved in this study, all workers had noise doses below the OSHA PEL (range 5.8% to 61.4%), and all but 2 workers (n = 35) had noise doses above the NIOSH REL (range 63.9% to 823.2%), indicating exposure to hazardous levels of noise based on more protective RELs.
Monitoring genetic diversity of Torminalis glaberrima for resilient forests in the face of population fragmentation
Authors: Afifi Lila , Szukala Aglaia , Klumpp Raphael , Tremetsberger Karin , Konrad Heino
Published: January 2025

Background and Aims

Torminalis glaberrima is a European tree species currently underutilized in forestry, valued for its high-quality wood and contribution to ecosystem stability. Despite a projected range expansion as climate change progresses, current population fragmentation levels may inhibit the species’ ability to migrate and stabilize fragile forest ecosystems. To investigate the relationship between structural and functional connectivity, we surveyed the genetic diversity, spatial genetic structure and gene flow of T. glaberrima across Austria, to understand which populations should be given conservation priority.

Methods

Our sampling encompasses 21 natural and planted populations and 910 individuals of T. glaberrima covering the species’ distribution in Austria. We estimated genetic diversity indices, the extent of gene dispersal, and conducted SPAGeDi and STRUCTURE analyses and discriminant analysis of principal components using one chloroplast minisatellite and eight nuclear microsatellite markers.

Key Results

Despite a highly fragmented distribution of T. glaberrima in the southern, western and central parts of its range in Austria, we found high genetic diversity and low population differentiation and inbreeding, and estimated higher gene dispersal values than previous studies. Population structure analyses identified two main regions of genetic ancestry in the north-western and south-eastern part of the species’ range in Austria and evidence for the usage of foreign genetic material in two planted populations.

Conclusions

Only two of the established ex situ plantations and seed orchards appear to well represent the fine-scale population structure present in Austria, and existing in situ gene conservation units (GCUs) are insufficient to conserve the current natural genetic diversity. We suggest the establishment of further in situ GCUs to maximize the conservation of extant forest genetic diversity. Additionally, we encourage corridor plantings between isolated populations, bolstering the genetic connectivity and diversity of populations.
Niche shifts and localized competitive dynamics influence the persistence and distribution of polyploids in the genus Achillea (Asteraceae)
Authors: Lu Wen-Xun , Tu Wen-Qin , Chen Duo , Wang Zi-Zhao , Guo Yan-Ping
Published: January 2025

Background and Aims

Competition with sympatric diploid progenitor(s) hinders the persistence of polyploids. The hypothesis that polyploids escape from competition through niche shifts has been widely tested; however, niche escape is unlikely to completely avoid competition. Given species growing in less favourable environments probably have weaker competitive abilities, we hypothesize that polyploid populations tend to persist in areas where their progenitors have relatively low habitat suitability.

Methods

This study investigated two sibling allopolyploid species, Achillea alpina and A. wilsoniana of the daisy family, which originated independently from the same two parental species. We explored the patterns of niche shifts between the polyploids and their progenitors by using several ecoinformatics analyses in environmental and geographical spaces, and performed ecological niche modelling to estimate the historical distribution of these species as well as the potential regions for persistence of allopolyploids.

Key Results

The niche shift patterns of the two polyploids were not completely consistent: A. alpina showed niche expansion, while A. wilsoniana exhibited a trend towards niche novelty. Their potential suitable areas were both more likely to overlap with regions where the habitat suitability values of their parental species became low.

Conclusions

The present results support our hypothesis that populations of polyploids tend to persist in areas that are less suitable for their diploid progenitors. Meanwhile, niche shifts may promote the success of polyploids. These findings contribute to our understanding of the ecological processes involved in the maintenance and persistence of polyploids.
Rosae multiflorae fructus extracts regulate the differentiation and vascular endothelial cell-mediated proliferation of keratinocytes
Authors: Asayama Sae , Igarashi Tami , Abe Yosihimi , Iwasaki Ayaka , Kubo Mizuki , Ikeda Ayaka , Akiyama Kouki , Okamoto Tadashi , Yagi Masayuki , Niki Yoko , Ando Hideya , Ichihashi Masamitsu , Mizutani Ken-ichi
Published: January 2025

Keratinocytes are the primary component of the epidermis, so maintaining the precise balance between proliferation and differentiation is essential for conserving epidermal structure and function. Rosae multiflorae fructus extract (RMFE) has wide application in the cosmetic industry, but the molecular mechanisms underlying beneficial effects on keratinocytes are still not fully understood. In this study, we found that RMFE promoted epidermal differentiation and enhanced the barrier function of normal human epidermal keratinocytes (NHEKs) and three-dimensional epidermis model in culture. In addition, RMFE promoted human umbilical vein endothelial cell (HUVEC) proliferation and angiogenesis, whereas the conditioned medium from RMFE-treated HUVECs further promoted NHEK proliferation and increased wound healing ability. Analysis of constituent bioactivities identified a quercetin derivative as a potential mediator of NHEK and HUVEC responses to RMFE. Taken together, these results suggest that RMFE enhances epidermal functions through both direct effects on keratinocytes and indirect effects mediated by endothelial cells.
Deep learning-based design and experimental validation of a medicine-like human antibody library
Authors: Rajagopal Nandhini , Choudhary Udit , Tsang Kenny , Martin Kyle P , Karadag Murat , Chen Hsin-Ting , Kwon Na-Young , Mozdzierz Joseph , Horspool Alexander M , Li Li , Tessier Peter M , Marlow Michael S , Nixon Andrew E , Kumar Sandeep
Published: January 2025

Antibody generation requires the use of one or more time-consuming methods, namely animal immunization, and in vitro display technologies. However, the recent availability of large amounts of antibody sequence and structural data in the public domain along with the advent of generative deep learning algorithms raises the possibility of computationally generating novel antibody sequences with desirable developability attributes. Here, we describe a deep learning model for computationally generating libraries of highly human antibody variable regions whose intrinsic physicochemical properties resemble those of the variable regions of the marketed antibody-based biotherapeutics (medicine-likeness). We generated 100000 variable region sequences of antigen-agnostic human antibodies belonging to the IGHV3-IGKV1 germline pair using a training dataset of 31416 human antibodies that satisfied our computational developability criteria. The in-silico generated antibodies recapitulate intrinsic sequence, structural, and physicochemical properties of the training antibodies, and compare favorably with the experimentally measured biophysical attributes of 100 variable regions of marketed and clinical stage antibody-based biotherapeutics. A sample of 51 highly diverse in-silico generated antibodies with >90th percentile medicine-likeness and > 90% humanness was evaluated by two independent experimental laboratories. Our data show the in-silico generated sequences exhibit high expression, monomer content, and thermal stability along with low hydrophobicity, self-association, and non-specific binding when produced as full-length monoclonal antibodies. The ability to computationally generate developable human antibody libraries is a first step towards enabling in-silico discovery of antibody-based biotherapeutics. These findings are expected to accelerate in-silico discovery of antibody-based biotherapeutics and expand the druggable antigen space to include targets refractory to conventional antibody discovery methods requiring in vitro antigen production.
Birds, stars, and mousikē: visions of escape in Euripidean choral odes
Authors: Reitzammer Laurialan
Published: January 2025

In this essay, I discuss, as a group, moments when a Euripidean female chorus express a wish for winged travel elsewhere—the second stasimon of Iphigenia among the Taurians (1089–1152),the third stasimon of Helen (1451–1511), the second stasimon of Hippolytus (732–75), and the first stasimon of Bacchae (370–431). These choral passages offer lengthy and elaborate escape prayers that embellish the conventional wish to take wing or disappear, focusing on the idea of wings and travel as opposed to the idea of disappearing, and offering a bird’s-eye view of imagined expanses of land and sea. In Euripides’ plays, as I argue, female choruses who wish for release from their impossible circumstances offer surprisingly similar visions of escape. Again and again, they wish to return home (to an actual home or to a notional homeland) and they yearn for winged travel to places characterized by bands of maidens and female mousikê (song, dance, and music).
Reconsidering the computer’s role in literary studies through Levison 1964
Authors: Rodda Martina Astrid
Published: January 2025

This article takes as its starting point a 1964 BICS article by Michael Levison and its scholarly context. From this piece, it traces the history of some key themes in Digital Humanities and computational approaches to classical texts: the availability of data and tools; the potential of different methods, from authorship attribution to textual reconstruction; and what questions they raise for the ethics of the field.
Functional profiling of the sequence stockpile: a protein pair-based assessment of in silico prediction tools
Authors: Prabakaran R , Bromberg Yana
Published: January 2025

Motivation

In silico functional annotation of proteins is crucial to narrowing the sequencing-accelerated gap in our understanding of protein activities. Numerous function annotation methods exist, and their ranks have been growing, particularly so with the recent deep learning-based developments. However, it is unclear if these tools are truly predictive. As we are not aware of any methods that can identify new terms in functional ontologies, we ask if they can, at least, identify molecular functions of proteins that are non-homologous to or far-removed from known protein families.

Results

Here, we explore the potential and limitations of the existing methods in predicting the molecular functions of thousands of such proteins. Lacking the “ground truth” functional annotations, we transformed the assessment of function prediction into evaluation of functional similarity of protein pairs that likely share function but are unlike any of the currently functionally annotated sequences. Notably, our approach transcends the limitations of functional annotation vocabularies, providing a means to assess different-ontology annotation methods. We find that most existing methods are limited to identifying functional similarity of homologous sequences and fail to predict the function of proteins lacking reference. Curiously, despite their seemingly unlimited by-homology scope, deep learning methods also have trouble capturing the functional signal encoded in protein sequence. We believe that our work will inspire the development of a new generation of methods that push boundaries and promote exploration and discovery in the molecular function domain.

Availability and implementation

The data underlying this article are available at https://doi.org/10.6084/m9.figshare.c.6737127.v3. The code used to compute siblings is available openly at https://bitbucket.org/bromberglab/siblings-detector/.
Semiparametric Sieve Estimation for Survival Data with Two-layer Censoring
Authors: Wang Yudong , Tong Jiayi , Hu Xiangbin , Ye Zhi-Sheng , Tang Cheng Yong , Chen Yong
Published: January 2025

Disease registry data provide important information on the progression of disease conditions. However, reports of death or dropout of patients enrolled in the registry are always subject to a noticeable delay. Reporting delays, together with the administrative censoring that arises from a freeze date in data collection, lead to two layers of right censoring in the data. The first layer results from random dropout and acts on the survival time. The second layer is the administrative censoring, which acts on the summation of the reporting delay and the minimum of the survival time and random dropout time. The heterogeneities among patients further complicate data analysis. This paper proposes a novel semiparametric sieve method based on phase-type distributions, in which covariates can be readily accommodated by the accelerated failure time model. A well-orchestrated EM algorithm is developed to compute the sieve maximum likelihood estimator. We establish the consistency and rate of convergence of the proposed sieve estimators, as well as the asymptotic normality and semiparametric efficiency of the estimators for the regression parameters. Comprehensive simulations and a real example of lung cancer registry data are used to demonstrate the proposed method. The results reveal substantial biases if reporting delays are overlooked.
An improved cell nuclear isolation method
Authors: Li Pengfei , Zhang Jingyao , Liu Xiaojuan , Wu Zhijuan , Kang Y James , Zhang Wenjing
Published: January 2025

Nuclear isolation is crucial for studying gene expression and regulatory mechanisms in eukaryotic cells. This study aimed to improve nuclear isolation and compare the yield, purity, and efficiency of several methods. Human umbilical vein endothelial cells were used to evaluate four different techniques: sucrose centrifugation, a simplified method, homogenization, and the NE-PER kit. For sucrose centrifugation, cells were scraped in Tween buffer, washed with sucrose buffer, and homogenized in a Dounce homogenizer. The pellet was washed with glycerol buffer to isolate the nuclei. In the simplified method, cells were scraped in scraping buffer, washed with sucrose buffer, and the pellet was washed with glycerol buffer to isolate the nuclei. For homogenization, cells were washed with phosphate buffered saline, followed by two washes in extract buffer and lysed with 10 strokes in a Kontes Dounce homogenizer. The NE-PER kit was used according to the manufacturer’s protocol. Nuclei isolated by each method were tested by immunoblotting, co-immunoprecipitation (Co-IP), and chromatin immunoprecipitation (Ch-IP) assays. The simplified method produced nuclei with fewer organelles and less cytoplasm than those isolated by homogenization or the NE-PER kit. It was similarly effective as sucrose centrifugation but faster. Co-IP and Ch-IP assays confirmed that the simplified method enriched target proteins and DNA fragments. Overall, the simplified method provides a highly pure nuclear sample optimal for downstream applications requiring purified nuclei.
Distributed lag models for retrospective cohort data with application to a study of built environment and body weight
Authors: Bobb Jennifer F , Mooney Stephen J , Cruz Maricela , Vernez Moudon Anne , Drewnowski Adam , Arterburn David , Cook Andrea J
Published: January 2025

Distributed lag models (DLMs) estimate the health effects of exposure over multiple time lags prior to the outcome and are widely used in time series studies. Applying DLMs to retrospective cohort studies is challenging due to inconsistent lengths of exposure history across participants, which is common when using electronic health record databases. A standard approach is to define subcohorts of individuals with some minimum exposure history, but this limits power and may amplify selection bias. We propose alternative full-cohort methods that use all available data while simultaneously enabling examination of the longest time lag estimable in the cohort. Through simulation studies, we find that restricting to a subcohort can lead to biased estimates of exposure effects due to confounding by correlated exposures at more distant lags. By contrast, full-cohort methods that incorporate multiple imputation of complete exposure histories can avoid this bias to efficiently estimate lagged and cumulative effects. Applying full-cohort DLMs to a study examining the association between residential density (a proxy for walkability) over 12 years and body weight, we find evidence of an immediate effect in the prior 1-2 years. We also observed an association at the maximal lag considered (12 years prior), which we posit reflects an earlier ($\ge$12 years) or incrementally increasing prior effect over time. DLMs can be efficiently incorporated within retrospective cohort studies to identify critical windows of exposure.
Beyond crisis and grief: Rethinking conservation narratives
Authors: Malavasi Marco
Published: January 2025

Since 1985, conservation science has been unquestioningly described as a crisis discipline. This narrative entails prioritizing immediate responses to threats despite limited knowledge. Although crisis interventions have grown significantly, biodiversity loss has continued unabated, and those working or living alongside declining ecosystems report increasing levels of emotional distress. Ecological grief is particularly on the rise and is claimed by some as a necessary process to fuel the urgent lifesaving changes. However, I argue that both narratives—the emerging ecological grief and the established crisis approach—can synergically reinforce a loop of resignation, where ecological decline is either passively accepted or inadvertently perpetuated. Such resignation ultimately leads to harmful adaptation to ongoing ecological degradation. Finally, I propose a shift toward a transformative conservation narrative, moving away from the primary focus on crisis thinking to embrace proactive futures. Reframing the underlying narratives is essential, because they can influence the broader conservation agenda.
The value of ultrasound measured rectus femoris thickness, cross-sectional area and shear wave velocity in assessment of muscle in postmenopausal women with osteosarcopenia
Authors: Chen Zi-Tong , Ge Jia-Ying , Jin Feng-Shan , Guo Le-Hang , Wang Qiao , Zhao Hui , Sun Li-Ping , Xu Hui-Xiong , Sheng Hui , Li Xiao-Long ,   China Alliance of Multi-Center Clinical Study for Ultrasound (Ultra-Chance)
Published: January 2025

Objectives

To evaluate the value of ultrasound (US) and shear wave velocity (SWV) to assess muscle in postmenopausal women with osteosarcopenia (OSP).

Methods

This study included 145 postmenopausal women, comprising 115 osteopenia/osteoporosis participants without sarcopenia (OP alone) and 30 OSP participants. All received the evaluation of bone mineral density (BMD), appendicular skeletal muscle mass index (ASMI), handgrip strength, calf circumference, 6-meter walking speed, and 5-time chair stand test. The cross-sectional area (RFcsa), thickness (RFthickness), and mean SWV of rectus femoris (RF) were measured by US and shear wave elastography. The clinical characteristics, RFcsa, RFthickness, and SWV, were compared between OP alone and OSP to determine the independent predictors of OSP. Receiver operating characteristic (ROC) curve analysis was used to evaluate the value of US and SWV for assessment of OSP.

Results

The RFcsa, RFthickness, SWV, and BMD of OSP were lower than those of OP alone (all P < 0.05). Through multivariate analysis, the diagnostic performance of the prediction model (area under the ROC curve, AUC, 0.917) composed of RFcsa and SWV was superior to RFcsa (AUC, 0.847), RFthickness (AUC, 0.797), and SWV (AUC, 0.740) alone. Moreover, the prediction model achieved 70.0% sensitivity, 93.0% specificity, and 88.3% accuracy.

Conclusions

The RFcsa, RFthickness, and SWV have potential value in assessing muscle in OSP and can be applied to routine clinical management of postmenopausal women.

Advances in knowledge

US measured RF thickness, CSA and SWV could assist detection and clinical management of OSP in postmenopausal women.
The impact of resective epilepsy surgery on the brain network: evidence from post-surgical imaging
Authors: Sainburg Lucas E , Englot Dario J , Morgan Victoria L
Published: January 2025

Resective epilepsy surgery can be an effective treatment for patients with medication-resistant focal epilepsy. Epilepsy resection consists of the surgical removal of an epileptic focus to stop seizure generation and disrupt the epileptic network. However, even focal surgical resections for epilepsy lead to widespread brain network changes. Understanding the impact of epilepsy surgery on the brain is crucial to improve surgical outcomes for patients. Here we provide a summary of studies imaging the postsurgical effects of epilepsy resection on the brain. We focus on MRI and PET studies of temporal lobe and pediatric epilepsy, reflecting the current literature. We discuss three potential mechanisms for surgery-induced brain changes: damage and degeneration, recovery, and reorganization. We additionally review the postsurgical brain correlates of surgical outcomes as well as the potential to predict the impact of surgery on an individual patient’s brain. A comprehensive characterization of the impact of surgery on the brain and precise methods to predict these brain network changes could lead to more personalized surgeries that improve seizure outcomes and reduce neuropsychological deficits after surgery.
Enhancing diabetic muscle repair through W-GA nanodots: a nanomedicinal approach to ameliorate myopathy in type 2 diabetes
Authors: Liu Shan , Wan Renwen , Li QingRong , Chen Yisheng , He Yanwei , Feng Xingting , Yung Patrick Shu-Hang , Luo Zhiwen , Wang Xianwen , Chen Chen
Published: January 2025

Objective

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder that significantly impairs muscle regeneration following injuries, contributing to numerous complications and reduced quality of life. There is an urgent need for therapeutic strategies that can enhance muscle regeneration and alleviate these pathological mechanisms. In this study, we evaluate the therapeutic efficacy of W-GA nanodots, which are composed of gallic acid (GA) and tungstate (W6+), on muscle regeneration in type 2 diabetes mellitus (T2D)-induced muscle injury, with a focus on their anti-inflammatory and antioxidative effects.

Methods

This study synthesized ultrasmall W-GA nanodots that were optimized for improved stability and bioactivity under physiological conditions. In vitro assessments included cell viability, apoptosis, reactive oxygen species (ROS) generation, and myotube differentiation in C2C12 myoblasts under hyperglycemic conditions. In vivo, T2D was induced in C57BL/6 mice, followed by muscle injury and treatment with W-GA. Muscle repair, fibrosis, and functional recovery were assessed through histological analysis and gait analysis using the CatWalk system.

Results

The W-GA nanodots significantly enhanced muscle cell proliferation, decreased ROS, and reduced apoptosis in vitro. In vivo, compared with the control group, the W-GA-treated group exhibited notably improved muscle regeneration, decreased fibrosis, and enhanced functional recovery. The treatment notably modulated the inflammatory response and oxidative stress in diabetic muscle tissues, facilitating improved regenerative dynamics and muscle function.

Conclusions

W-GA nanodots effectively counter the pathological mechanisms of diabetic myopathy by enhancing regenerative capacity and reducing oxidative stress and inflammation. This nanomedicine approach offers a promising therapeutic avenue for improving muscle health and overall quality of life in individuals suffering from T2D. However, further studies are needed to explore the clinical applications and long-term efficacy of these nanodots in preventing diabetic complications.
New Insights into the Quality Control Strategies of Inula racemosa Hook. F. (Pushkarmula) and Saussurea lappa Decne. (Kuth): Medicinal Crops of Alpine Himalaya
Authors: Kumar Manish , Bhardwaj Rishabh , Kumar Anil , Kumar Dinesh
Published: January 2025

Adulteration and illegal trade of Saussurea lappa in the name of Inula racemosa is a major issue. Therefore, accurate and easy methods are required to control malpractice and define authenticity. The current study is focused on authenticating and defining quality control methods for I. racemosa and S. lappa. Reference and market samples of S. lappa and I. racemosa were used to develop methods, including high-performance thin layer chromatography (HPTLC), Gas chromatography–mass spectrometry (GC-MS) and (Ultra Performance Liquid Chromatography-Photo Diode Array (UPLC-PDA). Multivariate analysis was used to define variations among samples. Costunolide, dehydrocostus lactone, isoalantolactone and alantolactone were used to develop and validate the quality control method. Phytochemical investigations and filter paper reagent tests clearly differentiate between Saussurea and Inula. HPTLC and GC–MS fingerprints were found significant to certify both species. From a quality control perspective, the UPLC-PDA method was found significant for the separation of targeted molecules. Altantolactones were found higher in I. racemosa while costunolides in S. lappa, whereas market samples closely resembled with Inula species and confirmed as I. racemosa. The current findings suggested that filter paper tests could be useful for farmers, traders and industries to check the authenticity of S. lappa and I. racemosa. Chemical fingerprints and UPLC-PDA method were found sufficient to define quality of both the species.
Transition dynamics of hybrid farmers: a survival analysis of exits and entries into full-time farming
Authors: Johansson Eleanor , Nilsson Pia , Hansson Helena
Published: January 2025

Using Swedish-matched employer–employee data from 2001 to 2018 and parametric survival analysis, we examine how the share of off-farm wage income affects survival time in the state of hybrid farming. We find a non-linear relationship between the share of off-farm wage income and the risk of exit; at lower levels, the share of off-farm wage income increases the risk of exiting agriculture completely and exiting from hybrid farming into full-time farming, while at higher levels it decreases the risk of exiting the hybrid state. This indicates that at higher levels of off-farm income, hybrid farming can be a stable state.
The interplay between scion genotype, root microbiome, and Neonectria ditissima apple canker
Authors: McLean Hamish , Mikaberidze Alexey , Deakin Greg , Xu Xiangming , Papp-Rupar Matevz
Published: January 2025

Severity of European apple canker caused by Neonectria ditissima can vary between locations and apple genotypes. We investigated how location, cold storage/planting season, and apple scion genotype affect root-associated microbial communities. Additionally, we investigated whether differences in abundance of specific taxa could be associated with canker lesion counts. Seven scion cultivars grafted onto M9 rootstocks were inoculated with N. ditissima in the nursery and then planted in December 2018 or stored at 2 °C until planting in April 2019 at three sites in Kent, UK. We assessed canker lesions and collected root samples in June 2021. Quantitative PCR and 16S/ITS amplicon sequencing was used to analyse microbial communities. Site was the primary factor affecting microbiome size, diversity, and composition. Cold storage/planting season had small but significant effects, indicating that differences in the microbiome at planting can persist long-term. Scion genotype had a limited effect on diversity but did influence the abundance of specific root associated taxa. Bacterial α-diversity was associated with canker count in a site-dependent manner. Increased abundances of particular fungal (Rhizophagus irregularis and Epicoccum nigrum) and bacterial (Amycolatopsis and Bradyrhizobium) root associated taxa were associated with fewer cankers.