bluuebunny/crossref_metadata_2025 huggingface dataset:
In vitro culture and confocal microscopy study of Maritrema gratiosum Nicoll, 1907 (Digenea): From metacercaria to ovigerous adult
Authors: Chuang YuChing , Shinn Andrew P. , Bron James E.
Published: January 2025

This study set out to characterise the in vitro development, including musculature, of the microphallid parasite of the barnacle Semibalanus balanoides (Linnaeus, 1767), Maritrema gratiosum Nicoll, 1907 collected in Scotland. An in vitro culture model was developed to obtain ovigerous adults of M. gratiosum and their morphology was observed. Different media were tested and NCTC-109 was chosen as the best medium. The effects of different concentrations of serum upon adult longevity, size and egg production was measured. Survival for 10-days was achieved when flukes were cultured in NCTC-109 plus chicken serum and antibiotics. Forty percent chicken serum seemed to provide better results in terms of survival time and producing flukes with the largest body lengths. Both normal and abnormal eggs were observed from adults cultured in vitro. Confocal microscopy was undertaken to provide details of the development of the parasite’s ultrastructure, including musculature, during the course of in vitro culture. While the musculature of M. gratiosum was similar to that of other microphallids, some additional novel structures were observed, most notably a ligament connecting pars prostatica and seminal vesicle and a racket-shaped excretory bladder. This study has provided greater insight into the biology M. gratiosum, and also developed a good in vitro model which might be applied to ecological or medical research in the future.
Human organoids for rapid validation of gene variants linked to cochlear malformations
Authors: Zafeer Mohammad Faraz , Ramzan Memoona , Duman Duygu , Mutlu Ahmet , Seyhan Serhat , Kalcioglu M. Tayyar , Fitoz Suat , DeRosa Brooke A. , Guo Shengru , Dykxhoorn Derek M. , Tekin Mustafa
Published: January 2025

Developmental anomalies of the hearing organ, the cochlea, are diagnosed in approximately one-fourth of individuals with congenital. The majority of patients with cochlear malformations remain etiologically undiagnosed due to insufficient knowledge about underlying genes or the inability to make conclusive interpretations of identified genetic variants. We used exome sequencing for the genetic evaluation of hearing loss associated with cochlear malformations in three probands from unrelated families deafness. We subsequently generated monoclonal induced pluripotent stem cell (iPSC) lines, bearing patient-specific knockins and knockouts using CRISPR/Cas9 to assess pathogenicity of candidate variants. We detected FGF3 (p.Arg165Gly) and GREB1L (p.Cys186Arg), variants of uncertain significance in two recognized genes for deafness, and PBXIP1(p.Trp574*) in a candidate gene. Upon differentiation of iPSCs towards inner ear organoids, we observed developmental aberrations in knockout lines compared to their isogenic controls. Patient-specific single nucleotide variants (SNVs) showed similar abnormalities as the knockout lines, functionally supporting their causality in the observed phenotype. Therefore, we present human inner ear organoids as a potential tool to validate the pathogenicity of DNA variants associated with cochlear malformations.

Graphical Abstract
Intra-individual comparison of long-term outcomes between combined and indirect bypass surgery in adult moyamoya disease
Authors: Chung Yuwhan , Kim Jeong Eun , Kang Hyun-Seung , Kim Tae Young , Paeng Jin Chul , Cho Won-Sang , Lee Sung Ho , Ha Eun Jin , Kim Kangmin
Published: January 2025

Purpose

Bypass surgery is regarded as the standard treatment option for symptomatic and hemodynamically unstable moyamoya disease (MMD). However, there is ongoing debate about the most effective type of bypass surgery. We aimed to analyze the long-term outcomes of combined and indirect bypasses for MMD patients through intra-individual comparisons.

Methods

Of the 896 patients who underwent 1084 bypass surgeries between 2007 and 2021, 24 patients with MMD who underwent combined bypass on one side and indirect bypass on the other side were ultimately enrolled in this study. Clinical, angiographic and hemodynamic outcomes were retrospectively evaluated.

Results

Three asymptomatic strokes (12.5%) occurred within 30 postoperative days in each group. Postoperative strokes after 30 days occurred in 3 patients (12.5%) with 3 hemorrhagic events and 1 cerebral infarction, only in indirect bypass, while no stroke occurred in hemispheres treated with combined bypass. The revascularization area relative to supratentorial area was significantly greater in combined bypass than in indirect bypass, both in short-term and long-term periods (64.9% versus 43.9% in short-term and 75.7% versus 54.9% in long-term; P < .001, respectively). Hemodynamic outcomes showed significantly greater increases in acetazolamide-challenged cerebral blood flow (CBFacz) during short-term follow-up (P = .04) and in both basal CBF (CBFbas) and CBFacz during long-term follow-up (P = .014 and P = .009, respectively) in combined bypass than in indirect bypass.

Conclusion

Combined bypass may be a more effective treatment option for MMD based on its higher revascularization area and favorable hemodynamic results compared to indirect bypass in the same patient.
Mild behavioral impairment in idiopathic REM sleep behavior disorder and Lewy body disease continuum
Authors: Jin Bora , Yoon Eun Jin , Woo Kyung Ah , Kim Seoyeon , Lee Seungmin , Kim Ryul , Shin Jung Hwan , Kim Yu Kyeong , Lee Jee-Young
Published: January 2025

To investigate the clinical impact of mild behavioral impairment (MBI) in a predefined cohort with Lewy body disease (LBD) continuum. Eighty-four patients in the LBD continuum participated in this study, including 35 patients with video-polysomnography-confirmed idiopathic REM sleep behavior disorder (iRBD) and 49 clinically established LBD. Evaluations included the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS), neuropsychological tests, and MBI Checklist (MBI-C). We examined the clinical associates of MBI-C and its diagnostic values in predicting disease severity and cognitive impairment across the LBD continuum. Participants were classified into 19 cognitively normal (CN), 45 mild cognitive impairment (MCI), and 20 dementia groups. Median MBI-C total scores were 1.0, 8.0, and 18.5 for CN, MCI, and dementia groups, respectively, with a significant increasing trend (p < 0.001). The MBI-C total score demonstrated significant correlations with the MDS-UPDRS part 1 (r = 0.504, p < 0.001) and total scores (r = 0.508, p < 0.001). Furthermore, significant correlations were observed between MBI-C and cognitive performances in frontal/executive (DSC: r = −0.314, p = 0.006; TMT-B: r = −0.338, p = 0.003) and attentional (TMT-A: r = −0.343, p = 0.002) domains. A cutoff 5.0 effectively differentiated the MCI from CN groups (area under the curve (AUC = 0.74). Furthermore, the MBI-C effectively discriminated the iRBD patients with high phenoconversion risk against those with low-risk (cut-off 4.0, AUC = 0.72). The MBI-C may be a useful screening questionnaire reflecting clinical severity across the LBD continuum. Longitudinal studies are needed to determine its value in monitoring disease progression in prodromal LBD.
Two experimental methods to integrate intra-oral scans into 3D stereophotogrammetric facial images
Authors: Schobben Reinout R.P. , Rangel Frits A. , Bruggink Robin , Crins - de Koning Marjolein L.D. , Bronkhorst Ewald M. , Ongkosuwito Edwin M.
Published: January 2025

Objectives

For this research two different ways for integrating intra-oral scans into three-dimensional (3D) stereophotogrammetric images are analyzed and compared to the gold standard method.

Materials and methods

A cross-sectional study was performed. For each patient a complete dataset was collected, which was used to generate 3D fusion models by three different methods: method A using cheek retractors, method B using a tracer and method C using full-skull CBCT. The experimental methods A and B were compared to the gold standard method C.

Results

A group of eighteen patients were included in this study. The translation (X, Y,Z), the euclidean distance and the rotation (roll, pitch, yaw) were calculated for both experimental methods A and B in comparison with the gold standard method C. Twelve out of fourteen measurements were clinically acceptable (below 2 mm or 2 degrees). Method A shows the highest deviation in the pitch-orientation for rotation (2.51 degrees, 95% CI [1.756 … 3.272]), while method B shows a higher deviation along the y-axis (1.85 mm, 95% CI [1.224 … 2.467]).

Conclusions

This study shows promising results of non-ionizing methods to integrate intra-oral scans into 3D stereophotogrammetric images. With improved accuracy in pitch in method A and translation along the Y-axis in method B, all measurements will be within the clinically acceptable threshold. However, since these two measurements exceed the clinically acceptable thresholds, the complete model positioning is less accurate. Therefore the main goal in further research should be to improve the accuracy of the pitch in method A and the translation along the Y-axis in method B. Additionally, for clinical use the biggest improvement could be gained by optimizing the clinical workflow and data processing.

Clinical relevance

By using a non-ionizing 3D fusion model instead of a conventional cephalogram for treatment planning, the ionizing dose during orthodontic treatment can be significantly reduced.
Reliability and validity of the Londrina activities of daily living protocol in individuals with systemic sclerosis
Authors: Gedikli Yasemin , Ozcan Kahraman Buse , Birlik Merih , Acar Serap , Savci Sema
Published: January 2025

Purpose

To investigate the validity and reliability of the Londrina ADL Protocol in patients with systemic sclerosis (SSc).

Methods

The study included 39 individuals with SSc and 30 healthy participants aged 18-70 years. Performance-related ADL assessment was performed with the Londrina ADL Protocol which was performed twice by the same rater and energy expenditure during the test with the Dynaport Move Monitor device. Functional capacity (6 Minute Walk Test-6MWT), upper extremity muscle strength (hand-held dynamometer), hand and finger grip strength (hand dynamometer and pinch meter), upper extremity functionality (Q-Dash Questionnaire and 9 Hole Peg Test), self-reported ADL (Milliken ADL Scale (MAS)) and quality of life (SF-36 questionnaire) were evaluated.

Results

Upper extremity muscle strength, functional capacity, upper extremity functionality, and quality of life of individuals with SSc were found to be significantly lower and the time spent by individuals with SSc in the Londrina ADL Protocol was lower and the time spent by individuals with SSc in the Londrina ADL Protocol was significantly longer compared to the healthy group (p<0.05). Performance in the the Londrina ADL had high intraclass correlation coefficient ICC=0.813. A moderate negative correlation was found between the time to complete the Londrina Protocol and 6MWT (p<0.05), and a weak negative correlation was found between dominant side hand grip strength (p<0.05) and MAS (p<0.05) in individuals with SSc. A moderate positive correlation was found between the Londrina Protocol and the 9-Hole Peg Test for the dominant side (p<0.05).

Conclusion

The Londrina Protocol is a valid and reliable method, hence, this makes it appropriate for an objective, performance-based evaluation of ADL in SSc population.

Key Points• The results obtained by reapplication the Londrina ADL Protocol under the same conditions showed that the Londrina ADL Protocol is a highly reliable assessment method in scleroderma patients.• Considering the activities and protocol content of the Londrina ADL Protocol, it is thought to show functional performance better than the Glittre ADL test and 6MWT.• The Londrina ADL Protocol is appropriate for objective and performance-based assessment of ADL in the SSc population for both research and clinical practice.
A Syndemic Clustering of Adversities on Suicide Risk among YMSM Living with HIV in Bangkok: A Causal Latent Class Analysis
Authors: Cheung Doug H. , Waratworawan Worawalan , Kongjareon Yamol , Jonas Kai J. , Lim Sin How , Reeves Alexis N. , Guadamuz Thomas E.
Published: January 2025

This study investigated the clustering of psychosocial adversities and their synergistic effect with depression on suicidality in a 12-month prospective cohort (N = 214) of YMSM living with HIV in Bangkok, Thailand. Latent class analysis identified subgroups with distinct combinations of adversities, including bullying, intimate partner violence, substance use, HIV stigma, low social support, histories of sex work, and below-income status. Significant interactive synergism were found as hypothesized, supporting a syndemic effect with qualitatively increasing levels of adversities on suicidality (score range: 3–17) over the 12 months. The interaction between moderate adversity clustering and depression (βow = 2.50, 95% CI: 1.12–3.88) and high adversity clustering and depression (βow = 3.61, 95% CI: 1.12–6.09) indicated that the impact of depression on suicidality was modified by pre-existing adversities. The findings suggest that, while a multi-component intervention addressing psychosocial problems is ideal, effective depression treatment alone could significantly reduce suicidality among YMSM living with HIV.
Employment Status and HIV Viral Load in Chilean Adult Population: A Propensity Score Analysis
Authors: Leiva-Escobar Ignacio , Cortes Claudia P. , Lamadrid Angelo
Published: January 2025

We set out to investigate the potential impact of unemployment on HIV viral load in individuals living with HIV at the biggest HIV-related healthcare centre in Chile. We analysed a cross-sectional dataset of 803 adults living with HIV on antiretroviral therapy. The main exposure was employment status. The outcome, detectable HIV viral load, was operationalised using a cut-off of HIV viral load at 20 copies/mL. We applied a propensity score method, the inverse probability of treatment weighting to control for measured confounders. We found that 219 (27.3%) of participants were unemployed. Being unemployed was associated with increased odds of being detectable (OR = 1.78, 95%CI = 1.18–2.71) compared to being employed. Additionally, we found that those unemployed and non-adherents have higher odds of being detectable (OR = 2.53, 95%CI = 1.18–5.41). Unemployment status may influence HIV viral load. However, further research is needed to determine and understand the social structure behind those relationships in the Chilean people living with HIV.
A Data-Driven Approach to Refine the Partially Stirred Reactor Closure for Turbulent Premixed Flames
Authors: Piu Lorenzo , Péquin Arthur , Freitas Rodolfo S. M. , Iavarone Salvatore , Pitsch Heinz , Parente Alessandro
Published: January 2025

Accurately predicting turbulent combustion processes is fundamental for optimizing efficiency, reducing pollutant emissions, and ensuring operational safety in combustion systems. To this purpose, computational fluid dynamics (CFD) simulations are widely employed. In particular, large eddy simulations (LES) balance prediction accuracy with computational efficiency by resolving only the most energy-containing scales of turbulence and rely on modeling the turbulence-chemistry interactions (TCI) occurring at the smallest scales. Among the existing closures, the partially stirred reactor (PaSR) model incorporates finite-rate chemistry and estimates a cell reacting fraction based on the local Damköhler number to account for the subfilter-scale TCI. Although widely validated in CFD computations, the PaSR model was found limited by the way it computes the cell reacting fraction. To tackle this point, our study proposes a machine learning (ML) enhanced partially stirred reactor model for LES. A fully connected neural network is trained on direct numerical simulation (DNS) data of turbulent premixed jet flames to compute a correction coefficient for the cell reacting fraction. Maintaining the original model shape, this ML-enhanced closure aims at bridging the gap between physics-based models and advanced data-driven techniques. The proposed formulation not only improves the prediction accuracy of quantities of interest such as the heat release rate but also features computational feasibility and generalisation capabilities over a large range of LES grid refinement. This demonstrates the significant potential of ML-aided TCI closures in future applications of combustion engineering.
Distributions of Wall Heat Flux and Wall Shear Stress and their Interrelation During Head-on Quenching of Premixed Flames within Turbulent Boundary Layers
Authors: Mohan Vishnu , Ahmed Umair , Chakraborty Nilanjan
Published: January 2025

The statistical behaviours of wall heat flux and wall shear stress and their interdependence during unsteady head-on quenching of statistically planar turbulent premixed flames within turbulent boundary layers due to heat loss through the cold wall have been analysed using three-dimensional Direct Numerical Simulation data with friction Reynolds numbers of $$Re_\tau =110$$

R

e
τ

=
110

and 180. In both cases, the mean wall shear stress decreases during flame-wall interaction, whereas the mean wall heat flux magnitude increases with time as the flame approaches the wall and eventually assumes a maximum value before decreasing with the progress of flame quenching. The integral length scales of wall heat flux in both streamwise and spanwise directions have been found to grow with time after the maximum mean heat flux magnitude is obtained for the two $$Re_\tau$$

R

e
τ

cases considered. However, the integral length scale of wall shear stress in the streamwise direction grows but the integral length scale of wall shear stress in the spanwise direction decreases with time after the maximum mean heat flux magnitude is reached. Moreover, the correlation coefficient between the wall heat flux magnitude and wall shear stress becomes increasingly negative while the mean wall heat flux increases with time, but this negative correlation weakens with the progress of flame quenching. The first few (i.e., most energetic) Proper Orthogonal Decomposition (POD) modes of wall shear stress and the wall heat flux magnitude have been found to capture the qualitative nature of the correlation between these quantities and their spatial variations. It is found that tens of most energetic POD modes are needed to capture the mean and variances of wall heat flux and wall shear stress. The number of most energetic modes, which contribute significantly to the statistics of both wall heat flux and wall shear stress, decreases with decreasing $$Re_\tau$$

R

e
τ

and also with the progress of flame quenching due to the weakening of turbulence effects.
Post-earthquake structural damage assessment, lessons learned, and addressing objections following the 2023 Kahramanmaras, Turkey earthquakes
Authors: Demir Aydin
Published: January 2025

This paper provides a comprehensive examination of post-earthquake structural damage assessment efforts following the Kahramanmaras, Turkey, earthquakes that occurred on February 6, 2023. Drawing on global damage assessment protocols, the study compares and analyzes the methods implemented in the aftermath of the earthquakes, offering insights into lessons learned and challenges faced. The analysis of objections raised regarding the assessment efforts reveals significant changes in structures with moderate and severe damage, emphasizing the need for continuous improvement in assessment strategies. The paper advocates for a realistic and two-stage application method, consideration of crack type and cause, and active involvement of local communities in the assessment process. Furthermore, the study identifies key issues in the current earthquake damage assessment methodology and proposes solutions, including a more precise classification system, regular volunteer training, consideration of secondary disaster risks, and effective communication methods. The paper concludes by underscoring the importance of effective damage assessment in disaster management, addressing objections from the affected population, and continual enhancement of strategies to improve resilience in earthquake-prone regions.
Dual targeting of HSP90 and BCL-2 in breast cancer cells using inhibitors BIIB021 and ABT-263
Authors: Gökşen Tosun Nazan , Kaplan Özlem
Published: January 2025

Purpose:

The incidence of breast cancer has been increasing in recent years, and monotherapy approaches are not sufficient alone in the treatment of breast cancer. In the combined therapy approach, combining two or three different agents in lower doses can mitigate the side effects on living cells and tissues caused by high doses of chemical agents used alone. ABT-263 (navitoclax), a clinically tested Bcl-2 family protein inhibitor, has shown limited success in clinical trials due to the development of resistance to monotherapy in breast cancer cells. This resistance shows that monotherapy approaches are inadequate and more effective treatment strategies are needed. It is the ability of HSP90 inhibitors to destabilize many oncoproteins that are critical for the survival of cancer cells. This study aimed to examine the anticancer activity of the combination of ABT-263 with BIIB021, a new generation HSP90 inhibitor, on two widely used breast cancer cell lines: MCF-7 (ER-positive) and MDA-MB-231 (triple-negative breast cancer, TNBC). These cell lines were selected to represent distinct breast cancer subtypes with different molecular characteristics and clinical behaviors.

Methods:

Single and combined cytotoxic effects of this agents on MCF-7 and MDA-MB-231 breast cancer cell lines were determined using the MTT cell viability test. The combined use of these two agents showed a synergistic effect, and this effect was assigned using the Chou and Talalay method. mRNA and protein levels of apoptosis-related genes Bax, Bcl-2, Casp9, and Heat Shock Proteins HSP27, HSP70, and HSP90 were analyzed using Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) and Western Blotting, respectively.

Results:

The cytotoxicity analysis, combined with the application of the Chou-Talalay method, demonstrated that the BIIB021 and ABT-263 combination exhibited significantly greater anticancer activity compared to the individual effects of either BIIB021 or ABT-263 in breast cancer cell lines. The analysis of mRNA and protein levels indicated that the BIIB021+ABT-263 combination may have triggered the intrinsic apoptotic pathway in breast cancer cells.

Conclusion:

This study showed that co-administration of ABT-263 and BIIB021 agents exhibited synergistic cytotoxic effects and increased the expression of apoptosis-related genes in breast cancer cell lines

Graphical abstract
Impact of declared wildfire disasters on survival of lung cancer patients undergoing radiation
Authors: Lichter Katie E. , Larson Bria , Pagadala Meghana , Mohamad Osama , Nogueira Leticia
Published: January 2025

Purpose

Oncological treatments, such as radiotherapy, which requires consistent electricity, the presence of specialized clinical teams, and daily patient access to treatment facilities, are frequently disrupted by extreme weather events, posing several health hazards to patients. This study explores the association between declared wildfire disasters during radiotherapy and overall survival among patients with non-small cell lung cancer (NSCLC).

Methods

The study population consisted of 202,935 adults with inoperable Stage III NSCLC, who initiated radiotherapy from 2004 through 2019. Exposure was defined as a wildfire disaster declaration in the county of the treatment facility within 12 weeks of initiating radiotherapy. Overall survival was defined as the interval (months) between age at diagnosis and age at death, date of last contact, or study end. Cox proportional hazards was used to estimate crude and adjusted hazard ratios and 95% confidence intervals with inverse probability weighting.

Results

Patients exposed to a wildfire disaster declaration during radiation treatment had worse overall survival (HR, 1.03; 95% CI 1.00–1.06; p = 0.02), compared to unexposed patients in adjusted models.

Conclusion

Exposure to a wildfire disaster during radiotherapy is associated with worse overall survival among patients with stage III non-operable NSCLC. This finding underscores the critical need for developing adaptation strategies within the healthcare sector, especially in oncology.
Temporal trends and patterns for early- and late-onset adult liver cancer incidence vary by race/ethnicity, subsite, and histologic type in the United States from 2000 to 2019
Authors: Hsieh Mei-Chin , Ratnapradipa Kendra L. , Rozek Laura , Wen Shengdi , Chiu Yu-Wen , Peters Edward S.
Published: January 2025

Purpose

To examine incidence trends and patterns for early- and late-onset liver cancer.

Methods

Liver and intrahepatic bile duct (IBD) cancers diagnosed between 2000 and 2019 were acquired from 22 SEER registries. Variables included early-onset (20–49) vs. late-onset (50+), anatomic subsite, histologic type (hepatocellular carcinoma [HCC] and IBD cholangiocarcinoma [ICC]), sex, and race/ethnicity. Age-standardized incidence rates were calculated using SEER*Stat. Jointpoint regression analysis was employed to estimate the annual percent change (APC) and the average APC (AAPC) with pairwise comparisons for trend by sex and by race/ethnicity stratified by age and subsite.

Results

Liver cancer incidence decreased among early-onset (AAPC [95% CI] − 2.39 [− 2.74, − 2.07]) but increased among late-onset patients (2.85 [2.71, 3.01]), primarily driven by HCC (3.60 [3.50, 3.71]). IBD incidence increased for both ages with ICC incidence annually increasing 7.92% (6.84, 9.26) for early-onset and 6.32% (5.46, 8.86) for late-onset patients. Early-onset liver cancer displayed comparable trends across racial/ethnic groups; however, late-onset liver cancer showed more variation, particularly among American Indian/Alaska Native/Asian Pacific Islander (AI/AN/API) populations, which experienced a significant decrease in incidence, thereby narrowing the gap with other racial/ethnic groups. For IBD, an identical pattern of early-onset IBD among non-Hispanic Blacks (NHBs) compared to Hispanics was showed with coincidence test p = 0.1522, and a parallel pattern was observed among late-onset patients for both sexes (p = 0.5087).

Conclusion

Late-onset HCC continues to rise, except for NHB and AI/AN/API, where incidence rates have started to decrease over the past 4–5 years. Early and late-onset ICC incidence continues to increase across all racial/ethnic groups.
Balancing Efficiency and Inequality in a Non-Linear Multi-Regional Water Allocation Optimization Model
Authors: Ortuzar Iban , Serrano Ana , Xabadia Angels , Brouwer Roy
Published: January 2025

Accounting for green and blue water resources, this study determines the optimal allocation of water between economic sectors under varying drought circumstances, applying non-linear optimization in a multi-regional input-output modeling framework. The results are compared to the regulated reallocation of water under existing regional drought warning and emergency plans. The analysis reveals that substantial economic gains can be achieved when considering efficiency in inter-sectoral water reallocation policies, mitigating value added losses. However, such optimal water allocation leads to greater inequality compared to the current drought policy measures. Extending the model and combining efficiency and equality concerns yields a production possibility frontier for second-best allocations that accounts for the distributional impacts of water reallocations under droughts. Notably, our findings demonstrate that there is potential for a more efficient distribution that is equal to the distributional impacts under the existing drought warning and emergency plans at lower total economic resource scarcity costs.
Unidirectional and bidirectional causation between smoking and blood DNA methylation: evidence from twin-based Mendelian randomisation
Authors: Singh Madhurbain , Dolan Conor V. , Lapato Dana M. , Hottenga Jouke-Jan , Pool René , Verhulst Brad , Boomsma Dorret I. , Breeze Charles E. , de Geus Eco J. C. , Hemani Gibran , Min Josine L. , Peterson Roseann E. , Maes Hermine H. M. , van Dongen Jenny , Neale Michael C.
Published: January 2025

Cigarette smoking is associated with numerous differentially-methylated genomic loci in multiple human tissues. These associations are often assumed to reflect the causal effects of smoking on DNA methylation (DNAm), which may underpin some of the adverse health sequelae of smoking. However, prior causal analyses with Mendelian Randomisation (MR) have found limited support for such effects. Here, we apply an integrated approach combining MR with twin causal models to examine causality between smoking and blood DNAm in the Netherlands Twin Register (N = 2577). Analyses revealed potential causal effects of current smoking on DNAm at > 500 sites in/near genes enriched for functional pathways relevant to known biological effects of smoking (e.g., hemopoiesis, cell- and neuro-development, and immune regulation). Notably, we also found evidence of reverse and bidirectional causation at several DNAm sites, suggesting that variation in DNAm at these sites may influence smoking liability. Seventeen of the loci with putative effects of DNAm on smoking showed highly specific enrichment for gene-regulatory functional elements in the brain, while the top three sites annotated to genes involved in G protein-coupled receptor signalling and innate immune response. These novel findings are partly attributable to the analyses of current smoking in twin models, rather than lifetime smoking typically examined in MR studies, as well as the increased statistical power achieved using multiallelic/polygenic scores as instrumental variables while controlling for potential horizontal pleiotropy. This study highlights the value of twin studies with genotypic and DNAm data for investigating causal relationships of DNAm with health and disease.
How knowledge of pathogen population biology informs management of Septoria nodorum blotch on wheat
Authors: McDonald Bruce A.
Published: January 2025

Septoria nodorum blotch (SNB) of wheat is caused by a complex of related fungi that infect both leaves and ears. The most intensively studied member of the species complex is Parastagonospora nodorum, which causes the majority of SNB. While P. nodorum is best known as a model pathogen for elucidating the inverse gene-for-gene interaction, knowledge of its population biology is also quite advanced. P. nodorum emerged as a wheat pathogen during the domestication of wheat in the Fertile Crescent. It then followed the spread of wheat agriculture around the world, likely moving on infected seed. Field populations around the world contain high levels of genetic and phenotypic diversity. This high diversity reflects the population biology of the fungus, which includes regular cycles of sexual recombination, high amounts of gene flow over regional scales, and large population sizes at the field scale. One hectare of a moderately infected field is estimated to contain about 1.8 million strains of P. nodorum that produce approximately 10 trillion spores that include about 70 million adapted mutant spores during a growing season. This standing diversity enables rapid adaptation to any selective agent, including deployments of fungicides and resistant cultivars. The key SNB management goal is to reduce the total pathogen population size, aiming to reduce the number of ascospores produced during and between growing seasons. One strategy that can be used to achieve this goal is to implement the practices of dynamic diversity across a regional scale.
Resilience of alpine lake macroinvertebrate communities to climate change: a view from the South Carpathian Mountains
Authors: Tombor E. , Korponai J. L. , Begy R. , Zsigmond A. R. , Wojewódka-Przybył M. , Hamerlík L. , Túri M. , Máthé I. , Kotrys B. , Płóciennik M. , Magyari E. K.
Published: January 2025

Remote mountain lakes experience accelerating ecological change worldwide due to the ongoing warming. In this study, we analyze two alpine lakes, Lake Ana (1940 m) and Lake Peleaga (2122 m), from the Retezat National Park in Romania. The sediment cores cover ~ 400 years, and our aim is to reconstruct critical transitions, the rate of ecosystem change and its driving factors. The extent of human disturbance is weak at these lakes today. Therefore, we assumed the principal role of summer warming in potential ecosystem reorganizations. For verifying this assumption, we use a multi-proxy approach including Pb210/Cs137 dating, chironomid, pollen, Cladocera analyses, SPDU, element concentration, organic matter, total nitrogen, C/N ratio and δ15N measurements, chord-distance-analysis (RoC) and chironomid-based temperature reconstruction. The assemblages indicated cold, oligotrophic environment and remained relatively stable despite climate change and human pressure, in contrast to assemblages studied from higher altitude (> 2300 m) lakes in the Alps. Our temperature reconstructions show warming from the 2000’s, but the results are influenced by fish introduction in the 1990s. We conclude that chironomid communities have not yet passed critical thresholds; the fauna reacted with restrained alterations, which is exceptional in the region, and highlight the importance of altitude and environmental protection.
Implementing Transitional Math: Perspectives of Illinois Community College Program Leaders
Authors: Hu Xiaodan , Creed Benjamin
Published: January 2025

In 2016, Illinois initiated a statewide transitional math program to support students to be academically ready in college-level math before graduating from high school. This qualitative study focuses on the perspective of community college faculty and administrators on the statewide implementation of transitional math programs. We find that a successful partnership between high schools and community colleges is perceived as key to designing, implementing, and improving transitional math programs to ensure effective teaching and learning. However, community college leaders perceived that it remains unclear how transitional math programs impact student success, college enrollment, and educational equity. We provided practical implications for both transitional math programs and the broader developmental education reform.
Nonhuman Well-Being is a Part of Happiness and Well-Being Conceptions Among Central Indian Indigenous Communities
Authors: Uotinen Joonas , Loivaranta Tikli , Seal Arunopol
Published: January 2025

The ontological turn in social sciences has revealed the anthropocentrism of earlier literature, but the role of interspecies relations in well-being ideals remains less explored. We examine the role of interspecies relations in well-being conceptions. The study is conducted among Indigenous communities to capture alternative human realities to those mainly reflected in the academic well-being literature. The study asks: what are the perspectives of selected Indian Indigenous communities on interspecies relations and well-being, and what is the role of the interspecies relations in their well-being and happiness conceptions? The research was conducted qualitatively using an immersive study technique, participatory observation and interviews, in eight villages in Central India. The material was analysed by participatory analysis and qualitative coding. The respondents form an ‘interspecies community’ with most of the nonhumans: the respondents had familial, reciprocal and caring relations with nonhumans, and perceived both the humans and nonhumans to similarly depend on a shared ecology. Such caring relations that relate to a sense of connection, and the well-being of the local humans and nonhumans were seen as important for human happiness. The caring relations towards the nonhumans, and sense of interdependency with the interspecies community tie the well-being of nonhumans to the local well-being conceptions. The local perspectives emphasize and respect the well-being of the nonhumans more than the predominant academic well-being conceptions.
Investigating Hearing Function in Paediatric Patients with Cancer in South Africa
Authors: Chauke Tlangelani Nyeleti , Khoza-Shangase Katijah
Published: January 2025

Paediatric cancer patients receiving platinum-based chemotherapy are at high risk of ototoxicity, often resulting in irreversible hearing loss. In South Africa, where healthcare resources are limited, routine audiological monitoring for this vulnerable population remains challenging, potentially leading to undiagnosed and untreated hearing impairments. To investigate hearing function in paediatric patients with cancer in South Africa. A descriptive, retrospective record review was conducted using patient data from two tertiary hospitals in Johannesburg: Chris Hani Baragwanath Academic Hospital and Charlotte Maxeke Johannesburg Academic Hospital. Audiological records for 47 paediatric cancer patients (ages 5–18) who had undergone baseline and follow-up hearing assessments were analysed. Descriptive and inferential statistics were used to examine hearing thresholds, tympanometry, and DPOAE results, with logistic regression assessing the association between cisplatin treatment and hearing loss. The study found that 36.2% of patients experienced high-frequency sensorineural hearing loss post-treatment, with significant threshold shifts at 4000–8000 Hz. Tympanometry indicated normal middle ear function in 87% of follow-up assessments, suggesting primarily cochlear damage. Logistic regression showed a significant association between cisplatin treatment and hearing loss, with an odds ratio of 3.18 (p = 0.003). DPOAE results further confirmed outer hair cell dysfunction, particularly in high frequencies, among patients who developed hearing loss. A substantial proportion of paediatric cancer patients in South Africa experience high-frequency hearing loss due to ototoxic treatments. These findings highlight the need for routine, standardized audiological monitoring protocols, particularly in resource-limited settings. Implementing early detection and management strategies can help mitigate the impact of hearing loss on language development, education, and quality of life in this vulnerable population.
DroughtStats: A comprehensive software for drought monitoring and analysis
Authors: Terzi Tolga Barış , Önöz Bihrat
Published: January 2025

The significance of drought monitoring and prediction systems has grown substantially due to the escalating impacts of climate change. However, existing tools for drought analysis face several limitations, including restricted functionality to single-variable indices, reliance on predefined probability distributions, lack of flexibility in choosing distributions, and the need for advanced programming expertise. These constraints hinder comprehensive and accurate drought assessments. This study introduces DroughtStats, a novel, user-friendly software designed to overcome these challenges and enhance drought analysis capabilities. DroughtStats integrates advanced statistical tools to analyze hydrometeorological data, compute both single-variable and multivariable drought indices using empirical and parametric methods, and evaluate drought characteristics with improved accuracy. Notably, it supports a broader range of probability distributions, performs copula-based analyses, and estimates potential evapotranspiration using multiple methods, including Penman–Monteith. Additionally, DroughtStats can analyze the relationship between different datasets using techniques like copula-based Kendall’s tau. By addressing the limitations of existing tools, DroughtStats provides a more flexible and comprehensive approach to drought monitoring. Its versatility and global applicability are demonstrated through a case study in Turkey’s Çoruh River Basin (CRB), where drought indices based on precipitation and streamflow are calculated to characterize drought conditions. The results show that DroughtStats can successfully identify and characterize drought events at various time scales, providing valuable insights into drought severity, frequency, and recovery, and offering a reliable tool for ongoing drought monitoring and management.
Socially Assistive Robot to Administer and Assess the Timed Up and Go Test: A Feasibility Study
Authors: Calabrese Carmela , Gower Valerio , Randazzo Mattia , Randazzo Marco , Brand Francesco , Mattos Fabiola Giovanna Mestanza , Spinelli Federico , Fussi Mattia , Landini Ettore , Bernagozzi Stefano , Natale Lorenzo
Published: January 2025

In standard clinical protocols, the result of neuromotor rehabilitation programs is evaluated through validated clinical scales and tests able to measure the motor performance of the patients and monitor their improvements over time. The Timed Up and Go (TUG) test is one of the most common assessments used to evaluate patients’ dynamic balance, as well as their mobility. However, in its traditional version, the TUG test does not provide quantitative information on gait performances—only subjectively observed by the clinician—and does not measure the timing of the different phases involved in its execution. The availability of additional quantitative information would indeed be useful for the clinicians to formulate a more accurate assessment of patient performance and define a personalized treatment plan. In this sense, the use of Socially Assistive Robots (SARs) could help improving the assessment of patient performance, relieving at the same time the physiotherapists from time consuming tasks. The goal of this feasibility study is twofold: (1) to assess the quality of the TUG functionality implemented on the robot from a technical standpoint and (2) to evaluate the perception of the “R1-TUG” solution from its potential end-users point of view, in terms of usability and acceptability. A set of tests involving a sample of healthy volunteers revealed that the adoption of a SAR as an assessment tool, could improve the ability of the physiotherapist to objectively assess the subject’s movement performance while ensuring an adequate level of usability and acceptability from the participants. This work represents a promising result for the future use of the robotic solutions within a rehabilitation context.
An accelerated Tseng type method for solving zero point problems and certain optimization problems
Authors: Mebawondu A. A. , Abass H. A. , Oyewole O. K.
Published: January 2025

In this paper, we proposed a modified Tseng’s splitting iterative algorithm for approximating a solution of split feasibility problem for zero and fixed point problems. By incorporating an inertial extrapolation method and Halpern iterative technique, we established a strong convergence result for approximating a solution of split fixed point problem for a nonexpansive and quasinonexpansive mapping which is also a zero point of sum of two monotone operators in the framework of real Hilbert spaces. Furthermore, we present a numerical example to support our main result. The results obtained in this paper improve, extend and unify some related results in the literature.
Lowballing Under the EU Takeover Bid Directive: Strategies, Concerns, and Gold-Plating Remedies
Authors: Mülbert Peter O. , Sajnovits Alexander
Published: January 2025

This paper investigates the phenomenon of lowballing within the context of the EU Takeover Bid Directive (TBD), where offerors set bid prices typically below the current market price. It delves into the key features of the TBD’s mandatory bid regime and examines the varied implementation approaches by Member States, including ‘gold-plating’ practices. The analysis encompasses strategies employed in both mandatory and voluntary bids, with prominent cases such as Porsche/VW and ACS/Hochtief serving as illustrative examples. The paper critically assesses the implications of low-cost control transactions, the pressure exerted on shareholders to accept undervalued offers, and the circumvention of or maneuvering around the TBD’s mandatory bid rule. The impact of lowballing on the Directive’s objectives, particularly the protection of minority shareholders, is thoroughly evaluated. Additionally, the study reviews gold-plating remedies adopted by Member States, such as supplementary bid requirements and mandatory minimum acceptance thresholds, and assesses their effectiveness and legal viability. The paper concludes with a discussion on the adequacy of current regulations in safeguarding minority shareholders and mentions potential reforms to address the persistent issue of lowballing within the EU framework.
Technical and economic feasibility analysis of a subsea shuttle tanker for CO2 transport to the troll field
Authors: Doust Arash Shahbazi , Undstad Fredrik Hovden , Klis Pawel , Xing Yihan , Ma Yucong
Published: January 2025

The Subsea Shuttle Tanker (SST) was presented by the authors as an innovative and cost-effective solution in several research works. This new approach offers a viable alternative to subsea pipelines and shuttle tanker ships for transporting liquid CO2 from onshore facilities to marginal offshore reservoirs. A previous technical–economic feasibility study found that the SST is generally economically competitive to the subsea pipelines and shuttle tanker ships for distances below 180 km and CO2 transport volumes of one million tons per annum (mtpa). The economic cost models are based on those developed in Maritime UN-manned Navigation through Intelligence in Network (MUNIN) D 9.3 and the Zero Emission Platform (ZEP) projects. This paper will take this previous study further by focusing on performing the technical and economic feasibility analysis for operation in the Troll field on the Norwegian continental shelf (NCS), which has a transport distance of 65 km and a CO2 volume of 1.5 mtpa. Two SST design solutions are investigated by downscaling and upscaling the reference baseline design to evaluate SST’s technical feasibility. Using the abovementioned cost models, the CO2 transportation cost per ton using SST is compared with subsea pipelines and tanker ships. The numerical results show that it is economically feasible to manufacture SST with cargo capacities of 4453 m3 and 2203 m3. Furthermore, the results show that the SST is the most cost-effective option for transporting low-volume CO2 (1.5 mtpa) over short distances.
Contribution to the design of cold bent glass
Authors: Laurs Maximilian , Feldmann Markus
Published: January 2025

Traditionally, curved façade geometries can be achieved by the means of hot bending glass or tessellation of the underlying geometry into plane parts, or even combinations of aforementioned. While the first method is not cost, nor energy efficient, for it relies on a heating process and requires bending moulds for every geometry, the second requires a vast amount of opaque substructure, opposing the aim of translucent façade structures. Contrary to these methods, the cold bending of glass omits those detrimental side effects of modern façade design. So, a promising technique was developed by elastically applying the curvature at ambient temperature. Nevertheless, the widespread use is still opposed by surmounted imponderables, like advanced calculation models utilizing FEAs and missing experience in the application of this method. This paper gives an extensive overview of the state of the art, like realized structures, deformation criteria and cold bending associated stress development, while also prompting a new analytical approach for the calculation of stresses in cold bent glasses. Moreover, a time-dependent buckling phenomenon on laminated glasses is discussed. In conclusion, aspects of the upcoming informative annex of the prEN 19100 (Eurocode 10 to be) on cold bending are discussed.