bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative analysis of regression algorithms for drug response prediction using GDSC dataset
Authors: Ha Soojung , Park Juho , Jo Kyuri
Published: January 2025

Background

Drug response prediction can infer the relationship between an individual’s genetic profile and a drug, which can be used to determine the choice of treatment for an individual patient. Prediction of drug response is recently being performed using machine learning technology. However, high-throughput sequencing data produces thousands of features per patient. In addition, it is difficult for researchers to know which algorithm is appropriate for prediction as various regression and feature selection algorithms exist.

Methods

We compared and evaluated the performance of 13 representative regression algorithms using Genomics of Drug Sensitivity in Cancer (GDSC) dataset. Three analyses was conducted to show the effect of feature selection methods, multiomics information, and drug categories on drug response prediction.

Results

In the experiments, Support Vector Regression algorithm and gene features selected with LINC L1000 dataset showed the best performance in terms of accuracy and execution time. However, integration of mutation and copy number variation information did not contribute to the prediction. Among the drug groups, responses of drugs related with hormone-related pathway were predicted with relatively high accuracy.

Conclusion

This study can help bioinformatics researchers design data processing steps and select algorithms for drug response prediction, and develop a new drug response prediction model based on the GDSC or other high-throughput sequencing datasets.
CRISPR/Cas9-editing of PRNP in Alpine goats
Authors: Allais-Bonnet Aurélie , Richard Christophe , André Marjolaine , Gelin Valérie , Deloche Marie-Christine , Lamadon Aurore , Morin Gwendoline , Mandon-Pépin Béatrice , Canon Eugénie , Thépot Dominique , Laubier Johann , Moazami-Goudarzi Katayoun , Laffont Ludivine , Dubois Olivier , Fassier Thierry , Congar Patrice , Lasserre Olivier , Aguirre-Lavin Tiphaine , Vilotte Jean-Luc , Pailhoux Eric
Published: January 2025

Misfolding of the cellular PrP (PrPc) protein causes prion disease, leading to neurodegenerative disorders in numerous mammalian species, including goats. A lack of PrPc induces complete resistance to prion disease. The aim of this work was to engineer Alpine goats carrying knockout (KO) alleles of PRNP, the PrPc-encoding gene, using CRISPR/Cas9-ribonucleoproteins and single-stranded donor oligonucleotides. The targeted region preceded the PRNP

Ter
mutation previously described in Norwegian goats. Genome editors were injected under the zona pellucida prior to the electroporation of 565 Alpine goat embryos/oocytes. A total of 122 two-cell-stage embryos were transferred to 46 hormonally synchronized recipient goats. Six of the goats remained pregnant and naturally gave birth to 10 offspring. Among the 10 newborns, eight founder animals carrying PRNP genome-edited alleles were obtained. Eight different mutated alleles were observed, including five inducing KO mutations. Three founders carried only genome-edited alleles and were phenotypically indistinguishable from their wild-type counterparts. Among them, one male carrying a one base pair insertion leading to a KO allele is currently used to rapidly extend a PRNP-KO line of Alpine goats for future characterization. In addition to KO alleles, a PRNP

del6
genetic variant has been identified in one-third of founder animals. This new variant will be tested for its potential properties with respect to prion disease. Future studies will also evaluate the effects of genetic background on other characters associated with PRNP KO, as previously described in the Norwegian breed or other species.
North American avian species that migrate in flocks show greater long-term non-breeding range shift rates
Authors: Vickers Stephen H. , Meehan Timothy D. , Michel Nicole L. , Franco Aldina M. A. , Gilroy James J.
Published: January 2025

Background

Many species are exhibiting range shifts associated with anthropogenic change. For migratory species, colonisation of new areas can require novel migratory programmes that facilitate navigation between independently-shifting seasonal ranges. Therefore, in some cases range-shifts may be limited by the capacity for novel migratory programmes to be transferred between generations, which can be genetically and socially mediated.

Methods

Here we used 50 years of North American Breeding Bird Survey and Audubon Christmas Bird Count data to test the prediction that breeding and/or non-breeding range-shifts are more prevalent among flocking migrants, which possess a capacity for rapid social transmission of novel migration routes.

Results

Across 122 North American bird species, social migration was a significant positive predictor for the magnitude of non-breeding centre of abundance (COA) shift within our study region (conterminous United States and Southern Canada). Across a subset of 81 species where age-structured flocking was determined, migrating in mixed-age flocks produced the greatest shifts and solo migrants the lowest. Flocking was not a significant predictor of breeding COA shifts, which were better explained by absolute population trends and migration distance.

Conclusions

Our results suggest that social grouping may play an important role in facilitating non-breeding distributional responses to climate change in migratory species. We highlight the need to gain a better understanding of migratory programme inheritance, and how this influences spatiotemporal population dynamics under environmental change.
Understanding the private-public school performance gap in PISA: evidence from Portugal
Authors: Colaço Ricardo , Freitas Pedro , Nunes Luis Catela , Reis Ana Balcão
Published: January 2025

We analyse the PISA-reported convergence in the performance of private and public schools in Portugal. When PISA sampling weights are used, the number of students enrolled in those types of schools and specific grades/tracks of study differs significantly from official population figures. To account for those differences, we apply a post-stratification adjustment; however, sample sizes are small, resulting in estimates with low precision for several subgroups. We propose recommendations for improving the handling of these issues in future PISA cycles. In an additional analysis, we also account for changes in the composition of the student population. When all factors are considered, the convergence in scores is far less impressive than reported. For instance, in Science, after adjusting the sampling weights and removing population composition effects, the reported convergence of 46 points between private and public schools from 2015 to 2018 amounts to only 9 points. The decomposition and sample adjustment methods used in this paper can be easily adapted to other contexts.
Age-dependent differences in the association between blood interleukin-6 levels and mortality in patients with sepsis: a retrospective observational study
Authors: Shimazui Takashi , Oami Takehiko , Shimada Tadanaga , Tomita Keisuke , Nakada Taka-aki
Published: January 2025

Background

Interleukin-6 (IL-6) is a cytokine that predicts clinical outcomes in critically ill patients, including those with sepsis. Elderly patients have blunted and easily dysregulated host responses to infection, which may influence IL-6 kinetics and alter the association between IL-6 levels and clinical outcomes.

Methods

This retrospective observational study included patients aged ≥ 16 years who were admitted to the intensive care unit at Chiba University Hospital. The patients were categorized into two groups: non-elderly (< 70 years) and elderly (≥ 70 years). Associations between log-transformed blood IL-6 levels and 28-day in-hospital mortality (primary outcome) and multiple organ dysfunction (MOD) on days 3 and 7 (secondary outcomes) were examined.

Results

The non-elderly and elderly groups included 272 and 247 patients, respectively. There were no significant differences in the Sequential Organ Failure Assessment score, components of the APACHE II score (Acute physiology score and Chronic health points), MOD at baseline, or any of the outcome measures between the groups. In the non-elderly group, univariate Cox regression analysis showed a significant association between IL-6 levels and mortality (hazard ratio [HR] 1.71, 95% confidence interval [CI] 1.25–2.37, P < 0.001). This association remained significant after adjusting for sex, body mass index, steroid use prior to sepsis onset, and number of chronic organ dysfunctions (HR 1.66, 95% CI 1.20–2.32, P = 0.002). However, no significant association was observed in the elderly group in either the univariate (P = 0.69) or multivariable analyses (P = 0.77). Multivariable logistic regression analysis of MOD on days 3 and 7 revealed significant associations between MOD and IL-6 levels in both groups.

Conclusions

Blood IL-6 levels were significantly associated with mortality in non-elderly patients with sepsis, but not in elderly patients. IL-6 levels were associated with MOD in both groups. Therefore, IL-6 levels should be interpreted with caution when predicting mortality in elderly patients with sepsis.

Trial registration: Not applicable.
Probabilistic estimation of rheological properties in subduction zones using sequences of earthquakes and aseismic slip
Authors: Köhne Tobias , Mallick Rishav , Simons Mark
Published: January 2025

Constraining the effective rheology of major faults contributes to improving our understanding of the physics of plate boundary deformation. Geodetic observations over the earthquake cycle are often used to estimate key rheological parameters, assuming specific laboratory-informed classes of viscous or frictional rheological models. However, differentiating between various rheological model classes using only observations of a single earthquake (coseismic and postseismic deformation) is difficult—especially in the presence of coarse spatiotemporal sampling, inherent observational noise, and non-uniqueness of the inverted properties. In this study, we present a framework to estimate key rheological parameters of a subduction zone plate interface using simulations of sequences of earthquakes and aseismic slip, constrained by pre- and postseismic surface displacement timeseries. Our simplified forward model consists of a two-dimensional subduction zone, represented by a discretized planar fault or narrow shear zone, divided into a locked, shallow region (“asperity”) experiencing periodically imposed coseismic events, and a stress-driven creeping section governed by power-law viscoelasticity or rate-dependent friction. Our inverse model fits the rheological parameters of the interface to surface displacement timeseries in a Bayesian probabilistic way. We validate that our proposed framework can successfully recover depth-dependent profiles of effective viscosity using a synthetic dataset of pre- and postseismic observations. Our first set of numerical experiments show that our framework is only mildly sensitive to uncertainties in the rupture history or assumed coseismic slip, making it robust enough to be applied to real observations of subduction zones. Our second set of tests considers the similarities of surface displacement timeseries between synthetic models that model the plate interface either as a shear zone described by power-law viscosity, or a surface described by rate-dependent friction. Here, we find that the ability to fit surface observations using functional or mechanical models assuming frictional behavior does not constitute sufficient evidence to actually infer frictional behavior at depth, as the surface expressions are virtually indistinguishable from deformation generated from models with depth-variable power-law viscous behavior. Based on our numerical experiments, we conclude that studies that aim to infer the mechanical behavior and rheological properties at depth in subduction zones should consider the surface expression from time periods representative of the entire seismic cycle.

Graphical Abstract
Investigating the impact of microbiome-changing interventions on food decision-making: MIFOOD study protocol
Authors: Vartanian Meghedi , Endres Konrad Jakob , Lee Yee Teng , Friedrich Silke , Meemken Marie-Theres , Schamarek Imke , Rohde-Zimmermann Kerstin , Schürfeld Robin , Eisenberg Lina , Hilbert Anja , Beyer Frauke , Stumvoll Michael , Sacher Julia , Villringer Arno , Christensen Julia F. , Witte A. Veronica
Published: January 2025

Background

Obesity is a multifactorial disease reaching pandemic proportions with increasing healthcare costs, advocating the development of better prevention and treatment strategies. Previous research indicates that the gut microbiome plays an important role in metabolic, hormonal, and neuronal cross-talk underlying eating behavior. We therefore aim to examine the effects of prebiotic and neurocognitive behavioral interventions on food decision-making and to assay the underlying mechanisms in a Randomized Controlled Trial (RCT).

Method

This study uses a parallel arm RCT design with a 26-week intervention period. We plan to enroll 90 participants (male/diverse/female) living with overweight or obesity, defined as either a Waist-to-Hip Ratio (WHR) ≥ 0.9 (male)/0.85 (diverse, female) or a Body Mass Index (BMI) ≥ 25 kg/m2. Key inclusion criteria are 18–60 years of age and exclusion criteria are type 2 diabetes, psychiatric disease, and Magnetic Resonance Imaging (MRI) contraindications. The interventions comprise either a daily supplementary intake of 30 g soluble fiber (inulin), or weekly neurocognitive behavioral group sessions, compared to placebo (equicaloric maltodextrin). At baseline and follow-up, food decision-making is assessed utilizing task-based MRI. Secondary outcome measures include structural MRI, eating habits, lifestyle factors, personality traits, and mood. Further, we obtain fecal and blood samples to investigate gut microbiome composition and related metabolites.

Discussion

This study relies on expanding research suggesting that dietary prebiotics could improve gut microbiome composition, leading to beneficial effects on gut-brain signaling and higher-order cognitive functions. In parallel, neurocognitive behavioral interventions have been proposed to improve unhealthy eating habits and metabolic status. However, causal evidence on how these “bottom-up” and “top-down” processes affect food decision-making and neuronal correlates in humans is still scarce. In addition, microbiome, and gut-brain-axis-related mediating mechanisms remain unclear. The present study proposes a comprehensive approach to assess the effects of these gut-brain-related processes influencing food decision-making in overweight and obesity.

Trial registration

ClinicalTrials.gov NCT05353504. Retrospectively registered on 29 April 2022.
Trusting the trustless blockchain for its adoption in accounting: theorizing the mediating role of technology-organization-environment framework
Authors: Seshadrinathan Sujata , Chandra Shalini
Published: January 2025

Blockchain technology has a unique ability to automate accounting processes that are a part of regulatory requirements in all commercial enterprises. Moreover, it can hold verified accounting records and eliminate the need for a trusted third party. Despite blockchain's potential to transform the nature of traditional accountancy procedures, adoption by the accounting industry is somewhat limited. Knowledge in this domain is lacking, and research on the antecedents influencing the adoption of blockchain-based accounting systems is scarce. This study is rooted in the technology-organization-environment (TOE) framework, presenting a trust-centric adoption model based on diligent analysis of blockchain and technology adoption literature. The model proposes that TOE factors mediate trust's role in adopting blockchain for accounting applications. The model was validated based on qualitative semi-structured interviews of twelve industry leaders and was comprehensively tested using a quantitative survey-based methodology with accounting professionals knowledgeable about blockchain technology. The data collected was analyzed using PLS-SEM. The results demonstrate the role of trust and the mediating effect of the theorized TOE variables on adopting blockchain-based accounting solutions. The results' implications for research and practice are discussed.
The impact of futures trade on the informational efficiency of the U.S. REIT market
Authors: Ahn Kwangwon , Jang Hanwool , Jeong Minhyuk , Sohn Sungbin
Published: January 2025

This study examines the impact of futures trading on market efficiency and price discovery in the U.S. real estate investment trusts (REITs) market. First, we present inconclusive evidence regarding efficiency improvement in the U.S. REIT spot market following the introduction of futures trading. To investigate the interplay between spot and futures markets, we analyze their respective roles in price discovery and find that, unlike in stock and bond markets, the spot market predominantly exhibits price leadership in the U.S. REITs market, despite the growing market size of futures. We find evidence that the limited role of futures in price discovery is associated with an increase in speculative demand, which outweighs hedging pressure. These findings suggest that policymakers should carefully monitor investor trading motives in the U.S. REITs market and consider revising market regulations to enhance liquidity, ensuring that increased liquidity does not primarily result from heightened speculative demand.
Qualitative financial modelling in fractal dimensions
Authors: El-Nabulsi Rami Ahmad , Anukool Waranont
Published: January 2025

The Black–Scholes equation is one of the most important partial differential equations governing the value of financial derivatives in financial markets. The Black–Scholes model for pricing stock options has been applied to various payoff structures, and options trading is based on Black and Scholes’ principle of dynamic hedging to estimate and assess option prices over time. However, the Black–Scholes model requires severe constraints, assumptions, and conditions to be applied to real-life financial and economic problems. Several methods and approaches have been developed to approach these conditions, such as fractional Black–Scholes models based on fractional derivatives. These fractional models are expected since the Black–Scholes equation is derived using Ito’s lemma from stochastic calculus, where fractional derivatives play a leading role. Hence, a fractional stochastic model that includes the basic Black–Scholes model as a special case is expected. However, these fractional financial models require computational tools and advanced analytical methods to solve the associated fractional Black–Scholes equations. Nevertheless, it is believed that the fractal nature of economic processes permits to model economical and financial markets problems more accurately compared to the conventional model. The relationship between fractional calculus and fractals is well-known in the literature. This study introduces a generalized Black–Scholes equation in fractal dimensions and discusses its role in financial marketing. In our analysis, we consider power-laws properties for volatility, interest rated, and dividend payout, which emerge in several empirical regularities in quantitative finance and economics. We apply our model to study the problem of pricing barrier option and we estimate the values of fractal dimensions in both time and in space. Our model can be used to obtain the prices of many pay-off models. We observe that fractal dimensions considerably affect the solutions of the Black–Scholes equation and that, for fractal dimensions much smaller than unity, the call option increases significantly. We prove that fractal dimensions are a powerful tool to obtain new results. Further details are analyzed and discussed.
Efficacy & safety of brolucizumab 6.0 mg versus 3.6 mg in diabetic macular edema
Authors: Mishra Sanjay Kumar , Kumar Pradeep , Joshi Amrita , Saraf Aman , Awasthi Abhijeet , Dhar Supriya , M Khaleel , Kumar Atul , Rana Vipin , D Ravi
Published: January 2025

Background

Management of Diabetic Macular edema (DME) requires repeated injections. Therefore newer Anti-VEGFs like Brolucizumab with longer durability have been introduced. We compared two different dosages of Brolucizumab, 6.0 mg and 3.6 mg, for their safety & efficacy in treatment of DME, in treatment naïve patients over 52 weeks.

Method

A prospective, pilot randomised controlled, single centre, double blinded, two arm comparative study was conducted between Dec 2022 to Apr 2024. The study recruited 82 patients of DME who were randomised into two groups of 41 patients each, one group to be treated with Brolucizumab 6.0 mg in 50 μL and the other to receive 3.6 mg in 30 μL. All patients received the first dose of Brolucizumab at 0 week and were then followed up at every 4 weeks for detailed ophthalmic and OCT macula examination. Those who met the pre-defined re-treatment criteria were re-injected with Brolucizumab, the dose being fixed for each group throughout the study. All patient receiving an injection were further followed up on Day 1, Day 7 and Day 28 to look for any adverse reactions. The efficacy parameters included change in best corrected visusal acuity (BCVA), contrast and central macular thickness (CMT) on Optical Coherence Tomography. The average number of injections recd in each group were also calculated.

Results

The change in BCVA from baseline in 6.0 mg group was 0.54 LogMAR units and 3.6 mg group was 0.59 LogMAR units, which was not statistically significant. The reduction in CMT from baseline in 6.0 mg group was 133.2 µm (μ) and 3.6 mg group was 110.6 μ, which was not statistically significant. The improvement in contrast from baseline in 6.0 mg group was 0.74 and 3.6 mg group was 0.95, with p value of 0.0002. The re-injection interval was 14.21 weeks in 6.0 mg group and 15.56 weeks for 3.6 mg subgroup. The total number of adverse events in both groups were similar at 70 in 6.0 mg group and 47 in 3.6 mg group with only one grade 4 adverse event occurring in each group.

Conclusion

The results of present study show that the safety and efficacy of both doses of Brolucizumab, i.e. 6.0 mg and 3.6 mg, for treating diabetic macular edema is similar.

Trial registration Study was registered with Clinical trials registry of India (CTRI ref no. CTRI/2023/06/054105), registered on 14 Nov 2022.
The 2024 clinical practice guidelines on the pharmacological management of Behavioural and Psychological Symptoms of Dementia (BPSD) in the Arab world
Authors: Bokhari Syed Ali , Qassem Tarik , Al-Ayyat Dania , Javaid Syed Fahad , Al-Sinawi Hamed , Nasr Walid
Published: January 2025

Background

Over 90% of individuals living with dementia experience behavioural and psychological symptoms of dementia, like agitation, anxiety, delusions, and sleep disturbances, which complicate care and place significant demands on healthcare systems. These guidelines are designed to meet the unique needs of dementia care in the Arab world, where dementia rates are increasing due to an ageing population.

Main body

These clinical practice guidelines provide evidence-based guidance tailored to the Arab World, with a focus on minimising unnecessary psychotropic use in dementia. The guidelines advocate a multi-pronged strategy, prioritising non-pharmacological interventions which are often safer and align well with local values and caregiving practices. Pharmacological treatments are recommended only for severe cases where symptoms cause distress or pose a risk to the patient or others. The guidelines cover key medication classes with detailed recommendations on dosage, side effects, and monitoring.

Conclusions

By integrating culturally appropriate, evidence-based strategies, these guidelines aim to enhance dementia care quality, incorporate the perspectives of patients and caregivers, support healthcare professionals, and promote safer, more effective management of dementia across diverse healthcare settings in the region.
Susceptibility of different mice species to chemical induction of colorectal cancer by 1,2-dimethylhydrazine
Authors: Abdelmaksoud Nourhan M. , Abulsoud Ahmed I. , Abdelghany Tamer M. , Elshaer Shereen Saeid , Samaha Ahmed , Maurice Nadine W. , Rizk Sherine Maher , Senousy Mahmoud A.
Published: January 2025

Background

Colorectal cancer (CRC) is a major public health concern. Animal models play a crucial role in understanding the disease pathology and development of effective treatment strategies. Chemically induced CRC represents a cornerstone in animal model development; however, due to the presence of different animal species with different genetic backgrounds, it becomes mandatory to study the susceptibility of different mice species to CRC induction by different chemical entities such as 1,2-dimethylhydrazine (DMH). This study aimed to investigate the induction receptivity of two commonly used mice species, C57BL/6 and BALB/c, to DMH-induced CRC.

Methods

Both mice species were exposed to weekly intraperitoneal injections of DMH at a dose of 20 mg/kg body weight for 15 consecutive weeks. The response to DMH was evaluated by monitoring body weight gain, daily food intake, and gastrointestinal symptoms. At the end of exposure, histopathology of distal colon dissected from both species was analyzed.

Results

Results revealed that C57BL/6 had a higher response to DMH compared to BALB/c. A significant decrease in body weight gain concomitant with severe diarrhea was observed in C57BL/6 receiving DMH compared to their controls, without any difference in food intake. Histopathology of distal colon revealed aberrant crypt foci and loss of goblet cells in DMH-exposed C57BL/6 mice. On the other hand, BALB/c mice displayed a normal and intact colon, with a normal weight gain pattern, and without any gastrointestinal symptoms.

Conclusion

In conclusion, C57BL/6 has a higher susceptibility toward chemical induction to CRC; therefore, it can be used to study CRC pathogenesis, prevention, and treatment.
Correlation between axial and coronal common bile duct diameters in computed tomography: a retrospective study of 1064 patients
Authors: Kasemassawachanont Adisak , Chuangsuwanich Natinee , Lertpipopmetha Wanicha , Panrong Nutthanun , Thusneyapan Kittipott , Tongsai Sasima , Noppakunsomboon Napakadol , Kaewlai Rathachai
Published: January 2025

Background

The measurement of the common bile duct (CBD) diameter is essential for evaluating bile duct pathologies. The axial plane of computed tomography (CT) images is the established method for CBD diameter measurement. However, modern software enables easy reconstruction of axial CT images into the coronal plane, allowing for CBD diameter measurement in this plane. This study aimed to investigate the correlation between measurements in the axial and coronal planes.

Results

The three reviewers demonstrated fair reliability in measuring CBD diameter in axial and coronal planes, with intraclass correlation coefficients of 0.776 and 0.799, respectively. A positive correlation was observed between the two diameters (r = 0.943), with 88.9% of axial diameter variation explained by coronal diameter and approximately 0.29 + (0.94 × coronal diameter) (R
2 = 0.889, p < 0.001). When a cutoff value of 7 mm was used to predict an abnormal axial diameter, the agreement between axial and coronal CBD diameters was substantial (Kappa = 0.715) with discordance between the two measurements identified in 6.2% of cases (66/1064) when a) coronal diameter < 7 mm but axial measurement  ≥ 7 mm (39/1064; 3.7%) and b) coronal diameter  ≥ 7 mm but axial measurement < 7 mm (27/1064; 2.5%). In univariable linear regression and multivariable analyses, the strongest independent factors associated with increased axial CBD diameter were presence of focal CBD lesion, age ≥ 60 years, and cholecystectomy.

Conclusion

There was a strong positive correlation between axial and coronal CBD diameters with substantial agreement when using a 7-mm cutoff and fair reliability in their measurements.
Evaluation of End-of-Life Quality Care Between American Indian and White North Carolina Decedents Diagnosed With Lung Cancer, 2003-2020
Authors: Jackson Bradford E. , Baggett Chris D. , Spees Lisa P. , Carrizosa Daniel , Emerson Marc A. , Fariman Soroush , Salas Ana I. , Bell Ronny A. , Wheeler Stephanie B.
Published: January 2025

PURPOSE

Lung cancer mortality rates for American Indians (AIs) are the highest among US race groups. End-of-life (EOL) care presents opportunities to limit aggressive and potentially unnecessary treatment. We evaluated differences in EOL quality of care between AI and White (WH) decedents with lung cancer.

METHODS

Our cohort included adult AI and WH decedents diagnosed with lung cancer (2003-2020) in North Carolina, who had health insurance claims during the month of and the month preceding death. EOL outcomes assessed during the last 30 days of life included intravenous chemotherapy, hospital admission, hospice initiation, ICU admission, >one emergency department (ED) visit, and in-hospital death. We used Poisson regression models to estimate risk ratios (RRs) and 95% CLs for each outcome comparing AI with WH, adjusting for rural/urban residence, age at diagnosis, insurance status, sex, histology, and diagnosis year. We also evaluated associations in the metastatic lung cancer subcohort.

RESULTS

Our cohort comprised 594 AI and 49,296 WH decedents. Compared with WH decedents, AIs were younger at diagnosis (66
v
71 years), more frequently Medicaid-insured (24%
v
11%), and more frequently rural residents (51%
v
30%). During the last 30 days of life, compared with WH decedents, AIs had higher risks of hospital admissions (RR, 1.14 [1.07-1.22]), ICU admissions (RR, 1.24 [1.08-1.42]), >one ED visits (RR, 1.27 [1.09-1.47]), and in-hospital death (RR, 1.22 [1.06-1.40]).

CONCLUSION

Indicators of inappropriate EOL care (hospital, ICU, and ED admissions) were notably higher during the last month of life for AI decedents with lung cancer. These findings highlight EOL care as an area where more interventions are needed to improve AI cancer care.
Environmental Enrichment Normalizes Metabolic Function in the Murine Model of Prader–Willi Syndrome Magel2-Null Mice
Authors: Queen Nicholas J , Zou Xunchang , Huang Wei , Mohammed Tawfiq , Cao Lei
Published: January 2025

Prader–Willi syndrome (PWS) is a rare genetic disease that causes developmental delays, intellectual impairment, constant hunger, obesity, endocrine dysfunction, and various behavioral and neuropsychiatric abnormalities. Standard care of PWS is limited to strict supervision of food intake and GH therapy, highlighting the unmet need for new therapeutic strategies. Environmental enrichment (EE), a housing environment providing physical, social, and cognitive stimulations, exerts broad benefits on mental and physical health. Here we assessed the metabolic and behavioral effects of EE in the Magel2-null mouse model of PWS. EE initiated after the occurrence of metabolic abnormality was sufficient to normalize body weight and body composition, reverse hyperleptinemia, and improve glucose metabolism in the male Magel2-null mice. These metabolic improvements induced by EE were comparable to those achieved by a hypothalamic brain-derived neurotrophic factor gene therapy although the underlying mechanisms remain to be determined. These data suggest biobehavioral interventions such as EE could be effective in the treatment of PWS-related metabolic abnormalities.
Zebra stripes induce aberrant motion analysis in flies through aliasing
Authors: Mouy Henri
Published: January 2025

The function of zebra stripes has long puzzled biologists: contrasted and conspicuous colours are unusual in mammals. The puzzle appears solved: two lines of evidence indicate that they evolved as a protection against biting flies, the geographical coincidence of stripes and exposure to trypanosomiasis in Africa and field experiments showing flies struggling to navigate near zebras. A logical mechanistic explanation would be that stripes interfere with analysis of the optic flow; however, both spatiotemporal aliasing and the aperture effect seem ruled out following recent experiments showing that randomly checked patterns also interfere with the ability of flies to navigate near zebras. No clear mechanistic hypothesis remains. Here, I model from first principles how flies assess their motion relative to stripes, from image forming to motion analysis. I show that, at short distances, flies would consistently misjudge the motion of a striped object and frequently and saliently misjudge the direction of movement of a randomised check pattern. The range of distances at which the model predicts that stripes should impair flies is consistent with observations. The model shows that image formation is subject to spatial aliasing, preventing any form of motion analysis against a striped pattern at medium distances. The motion computation of flies is subject to a second form of aliasing, which, although independent of the temporal resolution of flies, bears conceptual similarities to spatiotemporal aliasing. The findings highlight the necessity of accounting not only for processing and psychology but also for the optics of image formation when taking a perceptual perspective of animal colours and contrasts.
Linear Modelling of the V̇O 2 /PO-Relationship during Constant Work Rate Exercise
Authors: Stuer Lena , Boone Jan , Mucci Patrick , Colosio Alessandro L. , Bourgois Jan G. , Caen Kevin
Published: January 2025

Introduction

The linear and continuous increase in power output (PO) during ramp incremental (RI) exercise causes a distinct V̇O2/PO relationship compared to constant work rate (CWR) exercise. Current methods enabling a translation of ramp-derived PO to CWR PO assume a linear development of the CWR V̇O2/PO relationship in the heavy-intensity domain. This study aimed to model the RI versus CWR V̇O2/PO relationship to investigate whether the loss of mechanical efficiency above GET develops linearly. A second aim was to assess the reliability of ramp-derived parameters incorporated in translation strategies.

Methods

Fourteen healthy young participants (7 males; 7 females) performed a RI test and several CWR tests across the heavy- and severe-intensity domains in order to model the RI and CWR V̇O2/PO relationships. The CWR relationship was fitted using linear, polynomial and exponential models. Root mean square error (RMSE) and Akaike information criterion (AICC) were determined to evaluate the model’s goodness-of-fit. For reliability purposes, target PO of CWR tests were achieved using a preceding RI portion, similar to the initial RI test.

Results

The linear fit of the CWR V̇O2/PO relationship was associated with the lowest RMSE and AICC. The associated R2 for the heavy-intensity domain was 0.94. Reliability measures were excellent for baseline V̇O2 and acceptable to good for s
1-ramp and s
2- ramp. For MRT, a high variability was observed.

Conclusions

This study confirmed that the CWR V̇O2/PO relationship in the heavy-intensity domain is linear. Based on these results, it is justified to apply correction strategies that mind the different dynamics of V̇O2 during RI versus CWR exercise.
Μελέτη της δημιουργίας αντιγονο-ειδικών Β μνημονικών κυττάρων μετά από ανοσοποίηση με το 13-δύναμο συζευγμένο πολυσακχαριδικό πνευμονιοκοκκικό εμβόλιο σε υγιή βρέφη και παιδιά
Authors: Τζοβάρα Ειρήνη
Published: January 2025

Εισαγωγή: Τα εμβολιαστικά σχήματα έναντι του πνευμονιοκόκκου αξιολογούνται παραδοσιακά με βάση την αντισωματική τους απάντηση. Η εγκατάσταση της ανοσολογικής μνήμης που το καθένα εγκαθιστά, όπως αποτυπώνεται από τα Β Μνημονικά Κύτταρα (ΒΜΚ), δεν έχει μελετηθεί επαρκώς παρά το ρόλο της στην ισχύ και τη διάρκεια της προστασίας. Μέθοδοι: Στην παρούσα μελέτη συγκρίναμε τα τρία πιο ευρέως χρησιμοποιούμενα βρεφικά εμβολιαστικά σχήματα με το 13-δύναμο συζευγμένο πνευμονιοκοκκικό εμβόλιο (13-valent Pneumococcal Conjugate Vaccine, PCV13) ως προς την αντισωματική τους απάντηση αλλά και την ανοσολογική μνήμη που εγκαθιστούν και διερευνήσαμε τη σχέση μεταξύ των αντιγονο-ειδικών έναντι του πνευμονιοκόκκου (PS-ειδικών) BMK και της αντισωματικής απάντησης. Συγκεκριμένα, μελετήθηκε η συγκέντρωση των PS-ειδικών IgG αντισωμάτων και τα ολικά και PS-ειδικά BMK στο περιφερικό αίμα 42 βρεφών πριν και 1 μήνα μετά την τελευταία δόση του εμβολιαστικού σχήματος 3+0 (ομάδα Α), 2+1 (ομάδα Β) και 3+1 (ομάδα Γ). Μελετήθηκαν επίσης οι τρεις βασικοί υποπληθυσμοί των BMK, τα «κλασικά» (swIg), τα IgM+IgD- και τα «μη-κλασικά» (IgM+ IgD+) ΒΜΚ. Αποτελέσματα: Ο σχετικά ανώριμος υποπληθυσμός των «μη-κλασικών» (IgM+ IgD+) ΒΜΚ ήταν ο κυρίαρχος σε όλες τις ομάδες της μελέτης, αλλά το ποσοστό του ήταν υψηλότερο στα νεαρότερα βρέφη (6 μηνών) της ομάδας Α σε σύγκριση με τα μεγαλύτερα παιδιά των ομάδων Β και Γ (≥12 μηνών), υποδεικνύοντας ότι η ηλικία μπορεί να αποτελεί σημαντική παράμετρο της σύνθεσης της δεξαμενής των ΒΜΚ. Τα PS-ειδικά ΒΜΚ πριν την τελευταία δόση του PCV13 για το κάθε σχήμα ήταν υψηλότερα στην ομάδα Α, αλλά 1 μήνα μετά αυξήθηκαν σημαντικά μόνο στα σχήματα που περιλάμβαναν αναμνηστική δόση (ομάδες Β και Γ). Τα IgM+IgD- και τα «κλασικά» (swIg) PS-ειδικά ΒΜΚ πριν την τελευταία δόση συσχετίστηκαν θετικά με την αντισωματική απάντηση 1 μήνα αργότερα. Επιπλέον, τα IgM+IgD- PS-ειδικά ΒΜΚ πριν συσχετίστηκαν θετικά και με τα «κλασικά» (swIg) PS-ειδικά ΒΜΚ μετά την τελευταία δόση για το κάθε σχήμα. Συμπέρασμα: Τα ευρήματά της παρούσας μελέτης αναδεικνύουν τη σημασία της αναμνηστικής δόσης για τον εμπλουτισμό της PS-ειδικής ανοσολογικής μνήμης. Υπογραμμίζουν επίσης την σημασία του αριθμού των δόσεων αλλά και της ηλικίας κατά τον αρχικό εμβολιασμό στην εγκατάσταση ισχυρής κυτταρικής ανοσίας. Τέλος, αναδεικνύουν τα IgM+IgD- και τα «κλασικά» (swIg) ΒΜΚ ως εν δυνάμει πρόσθετους ανοσολογικούς δείκτες του μεγέθους και της διάρκειας της προστασίας που επάγεται από τον εμβολιασμό.
Roman copies of sculptural types of classical and Hellenistic periods from Macedonia
Authors: Φάτιμα Σιλβέστρο
Published: January 2025

Η παρούσα μελέτη στοχεύει στη συλλογή και εξέταση ρωμαϊκών αντιγράφων κλασικών και ελληνιστικών αγαλμάτων τύπων που βρέθηκαν στην περιοχή της αρχαίας ρωμαϊκής επαρχίας της Μακεδονίας. Πιο συγκεκριμένα, σκοπός της μελέτης μου είναι να διερευνήσω το φαινόμενο των αντιγράφων σε ιδιωτικά, δημόσια, ιερά και ταφικά πλαίσια εξετάζοντας υλικά που συλλέγονται από όλες τις περιοχές της Μακεδονικής Επαρχίας. Τα υλικά αποδεικτικά στοιχεία αποτελούνται από ολόσωμα μαρμάρινα και χάλκινα γλυπτά, ανάγλυφα γλυπτά και τερακότα. Τα χρονολογικά όρια της έρευνας εκτείνονται από τη Ρωμαϊκή κατάκτηση, η οποία διήρκεσε από τη Μάχη της Πύδνας το 168 π.Χ., μέχρι την εποχή των Σεβεράν. Η γραπτή μου εργασία αποτελείται από πέντε κύρια κεφάλαια. Το πρώτο κεφάλαιο εστιάζει στην παρουσίαση του υλικού που εξετάστηκε για να έχουμε σαφής επισκόπηση του αριθμού αντιγράφων. Σε αυτή τη φάση, κάθε μνημείο έχει μελετηθεί ξεχωριστά για να αναγνωρίσει τον αγαλματικον τύπον που εκπροσωπείται. Ορισμένοι αγαλματικοί τύποι είναι γνωστοί μόνο από παραλλαγές. Αυτά αναλύθηκαν στο δεύτερο κεφάλαιο. Το τρίτο κεφάλαιο επικεντρώνεται στα αρχαιολογικά πλαίσια στα οποία βρέθηκαν τα αντίγραφα. Η διερεύνηση της λειτουργίας και της πολιτιστικής σημασίας των αγαλματικών τύπων που εκτίθενται στους δημόσιους και ιδιωτικούς χώρους των διαφόρων περιοχών της ρωμαϊκής επαρχίας της Μακεδονίας είναι ο πυρήνας αυτής της συζήτησης. Όλα αυτά τα στοιχεία αναλύονται ως μέρος της πολιτιστικής και θρησκευτικής ταυτότητας του πληθυσμού που τα παρήγαγε. Το τέταρτο κεφάλαιο λαμβάνει υπόψη την παραγωγή των αντιγράφων σε μερικά από τα μεγάλα κέντρα της επαρχίας όπου ο μεγαλύτερος όγκος των διαθέσιμων δεδομένων μας επιτρέπει να υποθέσουμε την παρουσία τοπικών εργαστηρίων που προέκυψαν κοντά στα λατομεία μαρμάρου. Το πέμπτο τελικό κεφάλαιο περιέχει τις αναλυτικές μου παρατηρήσεις. Η τελική συζήτηση αρχικά παρουσιάζει το θέμα σε σχέση με τις τέσσερις κύριες γεωγραφικές περιοχές και στη συνέχεια γενικότερα εστιάζοντας στις διαφορές και τις ιδιαιτερότητες κάθε περιοχής. Δεδομένης της πολυπλοκότητας και της απεραντοσύνης θέματος που εξετάστηκε, επεξηγηματικούς πίνακες έχουν εισαχθεί στο τέλος του τόμου.
Influence of auditory-based cognitive training on auditory resolution, executive function, and working memory skills in individuals with mild cognitive impairment – a pilot randomized controlled study
Authors: G Priya , MM Kishan , R VaniLakshmi , Krishnan Gopee
Published: January 2025

Background Age-related central auditory processing disorder and mild cognitive impairment (MCI) can be concomitant in older adults, making it difficult to communicate, especially in challenging listening conditions. This preliminary study investigated the efficacy of auditory-based cognitive training on the auditory processing abilities and cognitive functions of older adults with MCI. Methods In this randomized controlled trial twenty-two older adults with mild cognitive impairment (MCI) were randomly assigned to either an experimental (n=11) or a control group (n=11). The experimental group received 15 cognitive training sessions through tasks involving the auditory domain. The outcome measures of this study included auditory resolution (Temporal gap detection, frequency discrimination, and modulation detection) and cognitive measures (Trail making tests and digit recall), which were administered at three-time points (before training, post-training, and follow-up). The linear mixed model computed the effects of training on the outcome measures. Results A significant improvement was observed in the modulation detection threshold between baseline and follow-up and between post-training and follow-up sessions. However, GDT and FD thresholds did not reveal any statistically significant difference. In the trail making test, Part B showed consistent significance across the time points, whereas Part A and the delayed recall task showed no significant difference. Conclusion Auditory-based cognitive training may improve auditory processing and executive function in older adults with mild cognitive impairment (MCI). Trial registration CTRI/2019/01/017073, registered on 14.01.2019
Evolving regional trends in U.S. opioid-related mortality: Disparities and the impact of COVID-19 (1999-2023)
Authors: Rana Ricky , Leiken Ben , Murugan Vikram , Billion Taylor , Tauseef Abubakar , Abdul Jabbar Ali Bin
Published: January 2025

Background The opioid crisis is a public health challenge in the United States, significantly impacting mortality rates. This has been further exacerbated by COVID-19, contributing to a surge in substance use and overdose deaths. Methods Data from the CDC Wonder Database was used to identify opioid use-related deaths in the United States from 1999 to 2023. Crude and age-adjusted mortality rates (AAMR) were calculated across different geographic and demographic groups. Temporal trends in mortality were analyzed using the Joinpoint Regression Program. Annual percentage change (APC) and average annual percentage change (AAPC) in mortality rates were calculated. Results Opioid-related mortality surged during the COVID-19 period, with significant regional, racial, and state-level disparities. The Midwest region exhibited the highest AAPC from 1999 to 2023. State-specific analyses showed that West Virginia experienced the highest increase in AAMR from 1999 to 2023. Among racial groups, non-Hispanic American Indians/Alaska Natives had the highest AAPC from 1999 to 2023. Gender-specific analyses revealed that males had a higher AAPC from 1999 to 2023 than females. Conclusion The United States opioid crisis continued to escalate during the COVID-19 period, with significant increases in mortality across the regions. The highest AAPCs were seen in the Midwest and among non-Hispanic American Indians/Alaska Natives. These findings underscore the need for targeted interventions to account for trends in racial and regional disparities in opioid-related mortality that have increased during and post-COVID-19.
Russia’s War against Ukraine in 1917–20 (Ideological and Political Context)
Authors: Verstiuk Vladyslav
Published: January 2025

Adopting as a starting point Russia’s current war against Ukraine, the paper discusses the historical precedent of today’s events, i.e. the war between Soviet Russia and the Ukrainian People’s Republic, which was proclaimed after the Bolsheviks had seized power in Russia and the empire had disintegrated into separate state entities. The author probes into the policies implemented by the Bolshevik government along with the military occupation of Ukraine and analyses the successive stages of the Russian intervention. The paper is intended to show how the Bolsheviks strived to depict the war as an internal Ukrainian class-based conflict rather than a case of direct Russian military aggression. In this pursuit, the Bolsheviks created a pseudo-Ukrainian Soviet government as a banner for the operations of Russian troops. The paper discusses how the conflict developed, presents a brief description of the “war communism” policy led by the Bolsheviks in Ukraine in 1919–20 to justify the exploitation of its natural resources, especially food supplies, and presents an overview of the occupation of Ukraine and the establishment of the Bolshevik regime on its territory.
The Film Director Who Was a Spy. Jadwiga Plucińska (1908–1999): A Forgotten Pioneer of Polish Documentary Film
Authors: Szymański Karol
Published: January 2025

This article aims to recall Jadwiga Plucińska – a pre-war actress, during the Second World War, a secretary in the Warsaw office of Die Deutsche Wochenschau, and between 1946 and 1959, a director of some twenty documentaries and features for the Polish Newsreel, showing the social, cultural and moral changes first in Poland recovering from the devastation of war (especially in the so-called Recovered Territories), and then during the ‘56 October Thaw. Her career was interrupted in 1959 by her arrest and subsequent five-year imprisonment on a charge of spying for US intelligence. As a result, Plucińska was almost completely forgotten and erased from the pages of Polish cinema history, and her work, withdrawn from distribution since the late 1950s, remains virtually unknown.
The Paradoxes of Eurasianism. George Vernadsky, Exile Networks, and the Origins of American Ukrainian Studies
Authors: Avramchuk Oleksandr
Published: January 2025

The article delves into a little-known role played by historian George Vernadsky, a prominent figure in the Eurasian intellectual movement, in shaping Ukrainian studies in North America both during and following the Second World War. By conducting research in the historian’s personal archives, it examines his extensive intellectual evolution – from his earlier strongly anti-Ukrainian views during the interwar period to his subsequent transformation into a fervent supporter of Ukrainian culture and history. Additionally, the article explores how his network of non-Russian connections played a crucial part in facilitating this transition.