bluuebunny/crossref_metadata_2025 huggingface dataset:
Outcomes of Bypass Surgery in Adult Moyamoya Disease by Onset Type
Authors: Lim Yong Cheol , Lee Eunyoung , Song Jihye
Published: June 2024

Importance

Moyamoya disease (MMD) is a rare chronic cerebrovascular disease, and the outcomes of bypass management in adult patients remain controversial.

Objective

To categorize adult MMD based on asymptomatic, ischemic, and hemorrhagic onset and compare the outcomes (death, hemorrhagic stroke [HS], and ischemic stroke [IS]) of bypass surgery (direct or indirect) with those of conservative management.

Design, Setting, and Participants

This retrospective, nationwide, population-based longitudinal cohort study used Korean National Health Insurance Research data to identify adults (aged ≥15 years) with MMD who were diagnosed between January 1, 2008, and December 31, 2020, and followed up until December 31, 2021 (median follow-up, 5.74 [IQR, 2.95-9.42] years). A total of 19 700 participants (3194 with hemorrhagic, 517 with ischemic, and 15 989 with asymptomatic MMD) were included. Data were analyzed from January 2 to April 1, 2023.

Exposures

Bypass surgery and conservative management.

Main Outcomes and Measures

Death constituted the primary outcome; secondary outcomes consisted of HS or IS. Kaplan-Meier survival curve and Cox proportional hazards regression analysis were applied. The propensity score–matching and stratified analyses were performed to control covariate effects.

Results

A total of 19 700 patients (mean [SD] age, 45.43 [14.98] years; 12 766 [64.8%] female) were included. Compared with conservative management, bypass was associated with a reduced risk of death (adjusted hazard ratio [AHR], 0.50 [95% CI, 0.41-0.61]; P < .001) and HS (AHR, 0.36 [0.30-0.40]; P < .001) in hemorrhagic MMD; reduced risk of IS (AHR, 0.55 [95% CI, 0.37-0.81]; P = .002) in ischemic MMD; and reduced risk of death (AHR, 0.74 [95% CI, 0.66-0.84]; P < .001) in asymptomatic MMD. However, bypass was associated with an increased risk of HS (AHR, 1.76 [95% CI, 1.56-2.00]; P < .001) in asymptomatic MMD. Both direct and indirect bypass demonstrated similar effects in hemorrhagic and asymptomatic MMD, except only direct bypass was associated with a reduced risk of IS (AHR, 0.52 [95% CI, 0.33- 0.83]; P = .01) in ischemic MMD. After stratification, bypass was associated with a reduced risk of death in patients younger than 55 years with ischemic (AHR, 0.34 [95% CI, 0.13- 0.88]; P = .03) and asymptomatic (AHR, 0.69 [95% CI, 0.60-0.79]; P < .001) MMD, but an increased risk of HS in patients 55 years or older with ischemic MMD (AHR, 2.13 [95% CI, 1.1-4.16]; P = .03).

Conclusions and Relevance

The findings of this cohort study of bypass outcomes for patients with MMD emphasize the importance of tailoring management strategies in adult patients based on onset types.
Preterm Birth, Family Income, and Intergenerational Income Mobility
Authors: Ahmed Asma M. , Pullenayegum Eleanor , McDonald Sarah D. , Beltempo Marc , Premji Shahirose S. , Shoukry Roaa , Pole Jason D. , Bacchini Fabiana , Shah Prakesh S. , Pechlivanoglou Petros
Published: June 2024

Importance

Preterm birth (PTB) has been associated with lower income in adulthood, but associations with intergenerational income mobility and the role of family socioeconomic status (SES) as modifying factor are unclear.

Objectives

To assess whether the association between PTB and income differs according to family SES at birth and to assess the association between PTB and intergenerational income mobility.

Design, Setting, and Participants

This study comprised a matched cohort of live births in Canada between January 1, 1990, and December 31, 1996, with follow-up until December 31, 2018. Statistical analysis was performed between May 2023 and March 2024.

Exposure

Preterm birth, defined as birth between 24 and 37 weeks’ gestational age (with gestational age subcategories of 34-36, 32-33, 28-31, and 24-27 weeks) vs early and full term births (gestational age, 37-41 weeks).

Main Outcomes and Measures

Associations between PTB and annual adulthood income in 2018 Canadian dollars were assessed overall (current exhange rate: $1 = CAD $1.37) and stratified by family income quintiles, using generalized estimating equation regression models. Associations between PTB and percentile rank change (ie, difference between the rank of individuals and their parents in the income distribution within their respective generations) and upward or downward mobility (based on income quintile) were assessed using linear and multinomial logistic regressions, respectively.

Results

Of 1.6 million included births (51.1% boys and 48.9% girls), 6.9% infants were born preterm (5.4% born at 34-36 weeks, 0.7% born at 32-33 weeks, 0.5% born at 28-31 weeks, and 0.2% born at 24-27 weeks). After matching on baseline characteristics (eg, sex, province of birth, and parental demographics) and adjusting for age and period effects, PTB was associated with lower annual income (mean difference, CAD −$687 [95% CI, −$788 to −$586]; 3% lower per year), and the differences were greater among those belonging to families in the lowest family SES quintile (mean difference, CAD −$807 [95% CI, −$998 to −$617]; 5% lower per year). Preterm birth was also associated with lower upward mobility and higher downward mobility, particularly for those born earlier than 31 weeks’ gestational age (24-27 weeks: mean difference in percentile rank change, −8.7 percentile points [95% CI, −10.5 to −6.8 percentile points]).

Conclusions and Relevance

In this population-based matched cohort study, PTB was associated with lower adulthood income, lower upward social mobility, and higher downward mobility, with greater differences among those belonging to economically disadvantaged families. Interventions to optimize socioeconomic outcomes of preterm-born individuals would need to define target population considering SES.
Precise Pore Engineering of Zirconium Metal‐Organic Cages for One‐Step Ethylene Purification from Ternary Mixtures
Authors: Feng Xueying , Wang Xiaokang , Yan Hui , Liu Hongyan , Liu Xiuping , Guan Jiayi , Lu Yukun , Fan Weidong , Yue Qin , Sun Daofeng
Published: June 2024

One‐step purification of ethylene from ternary mixtures (C2H2, C2H4, and C2H6) can greatly reduce the energy consumption of the separation process, but it is extremely challenging. Herein, we use crystal engineering and reticular chemistry to introduce unsaturated bonds (ethynyl and alkyne) into ligands, and successfully design and synthesized two novel Zr‐MOCs (ZrT‐1‐ethenyl and ZrT‐1‐alkyne). The introduction of carbon‐carbon unsaturated bonds provides abundant adsorption sites within the framework while modulating the pore window size. Comprehensive characterization techniques including single crystal and powder X‐ray diffraction, as well as electrospray ionization time‐of‐flight mass spectrometry (ESI‐TOF‐MS) confirm that ZrT‐1‐ethenyl and ZrT‐1‐alkyne possess an isostructural framework with ZrT‐1 and ZrT‐1‐Me, respectively. Adsorption isotherms and breakthrough experiments combined with theoretical calculations demonstrate that ZrT‐1‐ethenyl can effectively remove trace C2H2 and C2H6 in C2H4 and achieve separation of C2H2 from C2H4 and CO2. ZrT‐1‐ethenyl can also directly purify C2H4 in liquid solutions. This work provides a benchmark for MOCs that one‐step purification of ethylene from ternary mixtures.
Graphene‐Molecule Hybridization at a Ferromagnetic Interface
Authors: Cojocariu Iulia , Perilli Daniele , Feyer Vitaliy , Jugovac Matteo
Published: June 2024

The introduction of a graphene (Gr) buffer layer between a ferromagnetic substrate and a metallorganic molecule is known to mediate the magnetic coupling between them, an effect attributed to a weak hybridization between graphene and molecule. In this paper, we present experimental evidence of this effect through a detailed investigation of the frontier electronic properties of iron phthalocyanine deposited on cobalt‐supported graphene. Despite being physisorbed, the molecular adsorption on Gr/Co induces a sizeable charge transfer from graphene to the molecular macrocycle leading to the partial occupation of the LUMO and the appearance of an energetically localized hybrid state, which can be attributed to the overlap between the graphene pz state and the molecular macrocycle. Graphene is not inert either; the adsorption of the molecule induces doping and alters the Fermi velocity of both the hybrid minicone state and the Dirac cone. Similar effects are observed when the molecular periphery is decorated with fluorine atoms, known for their electron‐withdrawing properties, with minimal changes in the energy alignment.
LC–MS/MS quantification of olanzapine in hair after alkaline digestion
Authors: Turkmen Zeynep , Arslan Zeynep , Oka Merve , Yayla Murat , Bavunoglu Isil
Published: June 2024

Olanzapine (OLZ), a second‐generation antipsychotic drug, is effective in the treatment of acute psychosis, schizophrenia, agitation, bipolar mania, and other psychiatric problems. Antipsychotics are prescribed drugs, which lead the drug abuser to illegal methods of access. This behavior also demonstrates the association of OLZ with criminal involvement, commonly observed at forensic crime scenes. The acute toxicity and even death resulting from OLZ exposure have been highlighted in numerous studies. Therefore, developing analytical techniques to detect OLZ is essential for forensic toxicology. This study aimed to develop a specific and reliable LC–MS/MS method for OLZ detection and quantification in hair samples. The method was validated in terms of selectivity, linearity, limit of detection (LOD), limit of quantification (LOQ), trueness, precision, and uncertainty. The range of linearity was between 0.1–100 ng/mg, with LOD and LOQ values established at 0.036 ng/mg and 0.1 ng/mg, respectively. All validation results are within acceptable parameters. The validated method has been applied to authentic hair samples. The variation of OLZ concentrations in 12 hair segments (2 from Case 1 and 10 from Case 2) from two drug‐positive patients, ranging from 0.131 to 0.460 ng/mg, is presented in this study. Although several studies have been conducted to determine OLZ in hair samples using segmental analysis via hair solubilization, this study is the first to determine OLZ in hair samples after “digestion” with comparative parameters prior to chromatographic analysis.
Troubles with Seven Decades of Canadian/United States Oil Trade
Authors: Makholm Jeff D. , Olive Laura T.W.
Published: June 2024

In May 2023, we described the complexities of the energy market links between the United States and Canada due to national politics, US federal permitting policy, and the power of special interest groups.1 Yet, for more than a century, the US and Canada have worked through those challenges to develop an integrated North American energy market. Major energy infrastructure projects—pipelines and electric transmission lines—and an institutional ecosystem to foster competitive development of resources mean that energy trade between these two countries remains essential. Recent legal woes related to Enbridge Line 5 strain that relationship.2
Differential impacts of nonsteroidal anti‐inflammatory drugs on lifespan and healthspan in aged Caenorhabditis elegans
Authors: Tu Jia‐Jun , Yu Zhen‐Zhen , Ou Mei‐Ling , Cen Jin‐Xiong , Xue Kun , Zhou Jing , Li Shao‐Jun , Lu Guo‐Dong
Published: June 2024

Aging and age‐related diseases are intricately associated with oxidative stress and inflammation. Nonsteroidal anti‐inflammatory drugs (NSAIDs) have shown their promise in mitigating age‐related conditions and potentially extending lifespan in various model organisms. However, the efficacy of NSAIDs in older individuals may be influenced by age‐related changes in drug metabolism and tolerance, which could result in age‐dependent toxicities. This study aimed to evaluate the potential risks of toxicities associated with commonly used NSAIDs (aspirin, ibuprofen, acetaminophen, and indomethacin) on lifespan, healthspan, and oxidative stress levels in both young and old Caenorhabditis elegans. The results revealed that aspirin and ibuprofen were able to extend lifespan in both young and old worms by suppressing ROS generation and enhancing the expression of antioxidant SOD genes. In contrast, acetaminophen and indomeacin accelerated aging process in old worms, leading to oxidative stress damage and reduced resistance to heat stress through the pmk‐1/skn‐1 pathway. Notably, the harmful effects of acetaminophen and indomeacin were mitigated when pmk‐1 was knocked out in the pmk‐1(km25) strain. These results underscore the potential lack of benefit from acetaminophen and indomeacin in elderly individuals due to their increased susceptibility to toxicity. Further research is essential to elucidate the underlying mechanisms driving these age‐dependent responses and to evaluate the potential risks associated with NSAID use in the elderly population.
The quality of frozen–thawed Atlantic salmon (Salmo salar L.) fillets as affected by sub‐chilling before freezing
Authors: Lerfall Jørgen , Vangen Emma , Rotabakk Bjørn Tore
Published: June 2024

Background

To maintain the quality of frozen Atlantic salmon after thawing and highlight the potential for moving from air fright to boat for long‐distance export, a study was designed to investigate the effects of sub‐chilling before rapid freezing on the quality of thawed fillets. Atlantic salmon chilled on wet ice before filleting and freezing was used as a control for the experimental factor chilling, whereas fresh fillets were used for the frozen–thawed samples.

Results

The pre‐freezing chilling method interacted with the storage protocol and significantly affected the product. For fresh stored fillets, sub‐chilling improved the microbiological and textural stability and degradation of proteins. After 1 month of frozen storage, sub‐chilled fillets gave better color and textural properties, less adenosine triphosphate degradation and protein denaturation. In addition, sub‐chilled 4‐month‐frozen fillets also showed improved microbial stability compared to those initially chilled with ice before frozen storage. Quality was lost as a function of storage. Fresh fillets generally had higher bacterial counts, surface breaking force, firmness, hue and contents of inosine monophosphate, and lower drip loss and inosine (HxR) levels than those stored frozen–thawed. Moreover, 4‐month‐frozen fillets had higher HxR levels and lower psychrotrophic viable count growth than those that were frozen for 1 month. The time fillets were stored frozen did not profoundly affect their quality.

Conclusion

It is concluded that a frozen product might be competitive with a fresh product when sub‐chilling is performed before freezing, especially when including the environmental benefits of frozen export by boat rather than air freight. © 2024 The Author(s). Journal of The Science of Food and Agriculture published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
The Impact of Race and the Affordable Care Act on Thyroid Carcinoma Outcomes: A National Cancer Database Study
Authors: Nurimba Margaret , Sheth Megha , Swanson Mark , Chambers Tamara
Published: June 2024

Objective

To assess the impact of race and the Affordable Care Act (ACA) of 2010 on disease presentation and overall survival for patients with well‐differentiated thyroid carcinoma.

Study Design

Cross‐sectional study of patients (n = 51,078) who underwent partial or total thyroidectomy with or without postoperative radioactive iodine (RAI) for well‐differentiated thyroid carcinoma between 2004 and 2018 in the National Cancer Database (NCDB).

Methods

Cumulative survival (CS) was assessed with Cox proportional hazard regression analyses.

Results

There were significant disparities in disease presentation at the time of diagnosis, with Black, Asian/Pacific Islander (API), and Hispanic patients were more likely to have metastatic disease (p < 0.001) and higher TNM stage (p < 0.001) at the time of diagnosis compared to White patients. Black patients had significantly increased risk of death (HR 1.147, 95%CI 1.021–1.289) but API patients had improved CS (HR 0.730, 95% CI 0.608–0.877) compared to White patients. Passage of the ACA was associated with lower risk of mortality, regardless of whether patients lived in states that did not expand Medicaid (HR 0.866, 95% CI 0.823–0.910) or whether they lived in expansion states (HR 0.818, 95% CI 0.758–0.884).

Conclusion

Racial disparities significantly impact thyroid carcinoma diagnosis and treatment in the United States but have improved over time. Both expansion and non‐expansion states had improved survival outcomes over time, and suggesting analysis of the ACA's long‐term impact and ability to address health inequities is still warranted.

Level of Evidence

3 Laryngoscope, 134:4421–4430, 2024
A hemodynamic study of the relationship between the left and right liver volumes and the blood flow distribution in portal vein branches
Authors: Xie Chiyu , Sun Shengda , Huang Hao , Li Xiaofan , Qu Wei , Song Hongqing
Published: June 2024

Background

Cirrhosis patients often exhibit clinical symptoms such as right liver atrophy, portal hypertension, spleen enlargement and increased blood supply, which exhibit considerable variation between the left and right liver sections. These differences are hypothesized to stem from disparities in blood flow within the left and right portal vein (PV) branches. However, rigorous quantitative evidence remains scarce.

Purpose

We mainly aim at quantitatively revealing the relationship between the blood flow rates of two PV branches and liver volumes, and providing quantitative evidence and theoretical support for the diagnosis and treatment of cirrhosis from the perspective of hemodynamics.

Methods

Five cirrhotic patients and two healthy volunteers from Beijing Friendship Hospital are investigated. Their PV blood flow models are established based on computed tomography (CT) images and finite volume simulations. The volume of the left and right liver lobes are measured in 3‐matic. The distributions of blood source in the PV branches are tracked by streamline analysis. The blood flow rates are quantitatively counted by integrating the blood source velocities. Linear analysis is performed to build the relationship between liver volumes and PV blood flow distributions.

Results

Streamline analysis reveals significant differences in blood distribution between the left and right PV branches. The majority of blood from the superior mesenteric vein (SMV) flowed into the right portal vein (RPV), while most blood from the splenic vein (SV) entered the left portal vein (LPV). The main PV pressure drop linearly increases with the SV blood velocity for all PV structures of patients and healthy volunteers. The flow rate ratio QRPV/QLPV demonstrates an increase in tandem with the volume ratio VR/VL, exhibiting a linear correlation with the Pearson correlation coefficient being 0.93.

Conclusion

The differences in the blood distributions are consistent with the clinicians’ knowledge and validate our simulations. We demonstrated a linear increase in PV pressure with elevated SV blood velocity. Additionally, the volumes of the left and right hepatic lobes exhibited a positive correlation with blood flow rates in the corresponding PV branches.
Phase I study of the pharmacokinetics and safety of rezafungin in subjects with moderate/severe hepatic impairment and matched control subjects
Authors: Flanagan Shawn , Ong Voon , Marbury Thomas , Jandourek Alena , Gandhi Ronak G. , Sandison Taylor
Published: June 2024

Introduction

Rezafungin is a second‐generation, once‐weekly echinocandin antifungal approved for the treatment of invasive candidiasis, including candidemia. In phase II/III studies of rezafungin versus caspofungin, patients with severe hepatic impairment were excluded due to lack of caspofungin data in this population. This open‐label, single‐dose, phase I study evaluated the pharmacokinetics (primary objective) and safety of rezafungin in subjects with moderate or severe hepatic impairment versus matched, healthy subjects with normal hepatic function.

Methods

Eight subjects each with moderate (Child‐Pugh B) or severe (Child‐Pugh C) hepatic impairment were matched 1:1 with healthy subjects for age, sex, and body mass index. Each subject received a single 400‐mg, intravenous, 1‐h infusion of rezafungin. Plasma pharmacokinetic sampling was performed at various time points through 336 h postdose. Pharmacokinetic parameters were derived by non‐compartmental analysis. Safety was assessed throughout.

Results

All 32 subjects received study treatment and were included in all analyses. Despite overlapping distributions of total plasma concentrations, based on geometric least‐squares (LS) mean ratios, the area under the plasma concentration–time curve from time zero (prior to the start of infusion) to infinity (AUC0–∞) was 32% lower in subjects with moderate (LS mean ratio, 67.55; 90% confidence interval [CI]: 53.91, 84.65) and severe (LS mean ratio, 67.84; 90% CI: 57.49, 80.05) hepatic impairment versus matched healthy subjects. The maximum plasma concentration (Cmax) was 12% lower in moderate hepatic impairment and 28% lower in severe hepatic impairment groups. Linear regression showed no significant trend in the degree of hepatic impairment (based on Child‐Pugh score) on AUC0–∞ or Cmax (p > 0.05). Treatment‐emergent adverse events were reported in seven subjects (21.9%; three subjects in each of the hepatic impairment groups, and one healthy subject), none of which were severe, serious, or resulted in withdrawal.

Conclusions

Rezafungin is well tolerated and can be administered to patients with moderate or severe hepatic impairment without the need for dose adjustment. The modest reduction in exposures in subjects with hepatic impairment is not clinically meaningful and is unlikely to impact efficacy.
On energy and particle production in cosmology: the particular case of the gravitino
Authors: Casagrande Gabriele , Dudas Emilian , Peloso Marco
Published: June 2024

Abstract

It is well-known that the number of particles produced in cosmology, commonly defined in the literature from the Fock space of the instantaneous hamiltonian of the canonically normalized fields, is ambiguous. On the other hand, the energy computed from the energy-momentum tensor should be physical. We compare the corresponding Fock spaces and relate them through a Bogolyubov transformation. We find that for particles of spin 0, 1 and 3/2 the two Fock spaces are different, whereas they are the same for spin 1/2 fermions. For spin 0 and 1, for particles of high momenta the two Fock spaces align, as intuitively expected. For the spin 3/2, one finds two puzzles. The first one is that the two corresponding Fock spaces do not match even in the limit of high momenta. The second is that whereas we provide evidence for the equivalence theorem between longitudinal gravitinos and the goldstino in terms of an exact matching between the lagrangians and the instantaneous hamiltonians for the canonically normalized fields, the energy operator computed from the Rarita-Schwinger action does not seem to be captured in a simple way by the goldstino action. Our results suggest a re-analysis of non-thermal gravitino production in cosmology.
Seeing more than the Tip of the Iceberg: Approaches to Subthreshold Effects in Functional Magnetic Resonance Imaging of the Brain
Authors: Sundermann Benedikt , Pfleiderer Bettina , McLeod Anke , Mathys Christian
Published: June 2024

Many functional magnetic resonance imaging (fMRI) studies and presurgical mapping applications rely on mass-univariate inference with subsequent multiple comparison correction. Statistical results are frequently visualized as thresholded statistical maps. This approach has inherent limitations including the risk of drawing overly-selective conclusions based only on selective results passing such thresholds. This article gives an overview of both established and newly emerging scientific approaches to supplement such conventional analyses by incorporating information about subthreshold effects with the aim to improve interpretation of findings or leverage a wider array of information. Topics covered include neuroimaging data visualization, p-value histogram analysis and the related Higher Criticism approach for detecting rare and weak effects. Further examples from multivariate analyses and dedicated Bayesian approaches are provided.
3D large-scale forward modeling of gravitational fields using triangular spherical prisms with polynomial densities in depth
Authors: Ouyang Fang , Chen Long-wei , Wu Leyuan
Published: June 2024

To take the sphericity of the Earth into account, tesseroids are often utilized as grid elements in large-scale gravitational forward modeling. However, such elements in a latitude–longitude mesh suffer from degenerating into poorly shaped triangles near poles. Moreover, tesseroids have limited flexibility in describing laterally variable density distributions with irregular boundaries and also face difficulties in achieving completely equivalent division over a spherical surface that may be desired in a gravity inversion. We develop a new method based on triangular spherical prisms (TSPs) for 3D gravitational modeling in spherical coordinates. A TSP is defined by two spherical surfaces of triangular shape, with one of which being the radial projection of the other. Due to the spherical triangular shapes of the upper and lower surfaces, TSPs enjoy more advantages over tesseroids in describing mass density with different lateral resolutions. In addition, such an element also allows subdivisions with nearly equal weights in spherical coordinates. To calculate the gravitational effects of a TSP, we assume the density in each element to be polynomial along radial direction so as to accommodate a complex density environment. Then, we solve the Newton’s volume integral using a mixed Gaussian quadrature method, in which the surface integral over the spherical triangle is calculated using a triangle-based Gaussian quadrature rule via a radial projection that transforms the spherical triangles into linear ones. A 2D adaptive discretization strategy and an extension technique are also combined to improve the accuracy at observation points near the mass sources. The numerical experiments based on spherical shell models show that the proposed method achieves good accuracy from near surface to a satellite height in the case of TSPs with various dimensions and density variations. In comparison with the classical tesseroid-based method, the proposed algorithm enjoys better accuracy and much higher flexibility for density models with laterally irregular shapes. It shows that to achieve the same accuracy, the number of elements required by the proposed method is much less than that of the tesseroid-based method, which substantially speeds up the calculation by more than 2 orders. The application to the tessellated LITHO1.0 model further demonstrates its capability and practicability in realistic situations. The new method offers an attractive tool for gravity forward and inverse problems where the irregular grids are involved.
Incidence of diabetic retinopathy in anti-tnf treated rheumatic disease patients with type 2 diabetes
Authors: Baytaroğlu İffet Merve Uçar , Baytaroğlu Ata , Toros Merve Uçar , Daldal Hatice
Published: June 2024

Objective

This study aimed to evaluate the impact of anti-TNF (biological) therapies on the incidence and progression of diabetic retinopathy.

Materials and methods

A cross-sectional analysis of 50 diabetic patients with rheumatic diseases (group 1) was performed. An age-, sex-, and HbA1c-matched control group (group 2) was formed from a pool of diabetic patients who underwent regular eye examinations. The presence or absence of diabetic retinopathy was also assessed. Comorbidities such as hypertension, coronary artery disease, and hyperlipidemia were also evaluated as possible confounding factors.

Results

Hundred eyes of 50 patients were evaluated in each group. Only three patients in group 1 had non-proliferative retinopathy. The median duration of rheumatic disease was 9 years, whereas that of diabetes was 11 years. The mean duration of anti-TNF therapy was 4 years. In the control group of diabetes-only patients, 13 patients developed some form of newly diagnosed diabetic retinopathy during the last five years. The calculated retinopathy occurrence between the groups was statistically significant (p < 0.05). In this study, the incidence rate ratio for patients receiving anti-TNF treatment was calculated as 0.4 in the study.

Conclusion

TNF inhibitors, with their anti-inflammatory effects, positively impact diabetic complications by reducing the incidence of retinopathy. To our knowledge, this is the first study to evaluate retinopathy development after anti-TNF therapy.
AI-driven discovery of blood xenobiotic biomarkers in neovascular age-related macular degeneration using iterative random forests
Authors: Künzel Steffen E. , Frentzel Dominik P. , Flesch Leonie T. M. , Knecht Vitus A. , Rübsam Anne , Dreher Felix , Schütte Moritz , Dubrac Alexandre , Lange Bodo , Yaspo Marie-Laure , Lehrach Hans , Joussen Antonia M. , Zeitz Oliver
Published: June 2024

Purpose

To investigate the xenobiotic profiles of patients with neovascular age-related macular degeneration (nAMD) undergoing anti-vascular endothelial growth factor (anti-VEGF) intravitreal therapy (IVT) to identify biomarkers indicative of clinical phenotypes through advanced AI methodologies.

Methods

In this cross-sectional observational study, we analyzed 156 peripheral blood xenobiotic features in a cohort of 46 nAMD patients stratified by choroidal neovascularization (CNV) control under anti-VEGF IVT. We employed Liquid Chromatography—Tandem Mass Spectrometry (LC–MS/MS) for measurement and leveraged an AI-driven iterative Random Forests (iRF) approach for robust pattern recognition and feature selection, aligning molecular profiles with clinical phenotypes.

Results

AI-augmented iRF models effectively refined the metabolite spectrum by discarding non-predictive elements. Perfluorooctanesulfonate (PFOS) and Ethyl β-glucopyranoside were identified as significant biomarkers through this process, associated with various clinically relevant phenotypes. Unlike single metabolite classes, drug metabolites were distinctly correlated with subretinal fluid presence.

Conclusions

This study underscores the enhanced capability of AI, particularly iRF, in dissecting complex metabolomic data to elucidate the xenobiotic landscape of nAMD and environmental impact on the disease. The preliminary biomarkers discovered offer promising directions for personalized treatment strategies, although further validation in broader cohorts is essential for clinical application.
Lower plasma melatonin levels in non-hypoxic premature newborns associated with neonatal pain
Authors: Sánchez-Borja Cristina , Cristóbal-Cañadas Delia , Rodríguez-Lucenilla María Isabel , Muñoz-Hoyos Antonio , Agil Ahmad , Vázquez-López María Ángeles , Parrón-Carreño Tesifón , Nievas-Soriano Bruno José , Bonillo-Perales Antonio , Bonillo-Perales Juan Carlos
Published: June 2024

We analyzed plasma melatonin levels in different groups of preterm newborns without hypoxia and their relationship with several perinatal variables like gestational age or neonatal pain. Prospective cohort study of preterm newborns (PTNB) without perinatal hypoxia, Apgar > 6 at 5 min, and oxygen needs on the third day of life. We compared melatonin levels at day 3 of life in different groups of non-hypoxic preterm infants (Student’s t-tests, Mann-Whitney U, and chi2) and analyzed the relationship of melatonin with GA, birth weight, neonatal pain (Premature Infant Pain Profile (PIPP) scale), caffeine treatment, parenteral nutrition, or the development of free radical diseases (correlation study, linear regression) and factors associated with moderate/intense pain and free radical diseases (logistic regression analysis). Sixty-one preterm infants with gestational age (GA) of 30.7 ± 2.0 weeks with no oxygen requirements at day 3 of life were studied with plasma melatonin levels of 33.8 ± 12.01 pg/ml. Preterm infants weighing < 1250 g at birth had lower plasma melatonin levels (p = 0.05). Preterm infants with moderate or severe pain (PPIPP > 5) have lower melatonin levels (p = 0.01), and being preterm with PIPP > 5 is associated with lower plasma melatonin levels (p = 0.03). Being very preterm (GA < 32 GS), having low weight for gestational age (LWGA), receiving caffeine treatment, or requiring parenteral nutrition did not modify melatonin levels in non-hypoxic preterm infants (p = NS). Melatonin on day 3 of life in non-hypoxic preterm infants is not associated with later development of free radical diseases (BPD, sepsis, ROP, HIV, NEC).

Conclusion: We observed that preterm infants with moderate to severe pain have lower melatonin levels. These findings are relevant because they reinforce the findings of other authors that melatonin supplementation decreases pain and oxidative stress in painful procedures in premature infants. Further studies are needed to evaluate whether melatonin could be used as an analgesic in painful procedures in preterm infants.

Trial registration: Trial registration was not required since this was an observational study.

What Is Known:• Melatonin is a potent antioxidant and free radical scavenger in newborns under stress conditions: hypoxia, acidosis, hypotension, painful procedures, or parenteral nutrition.• Pain stimulates the production of melatonin.• Various studies conclude that melatonin administration decreases pain during the neonatal period.What Is New:• Non-hypoxic preterm infants with moderate to severe pain (PIPP>5) have lower levels of melatonin.• Administration of caffeine and treatment with parenteral nutrition do not modify melatonin levels in non-hypoxic preterm infants.
Acute effects of oral mesna administration on the full amino acid profile and 3-methylhistidine: secondary results from the CYLOB dose-finding study
Authors: Olsen Thomas , Elshorbagy Amany , Stolt Emma , Åsberg Anders , Zaré Hasse K. , Bastani Nasser E. , Refsum Helga , Retterstøl Kjetil , Vinknes Kathrine J.
Published: June 2024

Plasma total cysteine (tCys) is strongly associated with fat mass in humans. Mesna lowers plasma tCys in a dose-dependent manner, but it is not known whether it interferes with metabolism of other amino acids or protein. In this Phase-1 study, we show that a single dose of mesna administered at 400, 800, 1200 or 1600 mg to 6–7 individuals per dose only slightly affects amino acid profiles, with increases in plasma valine across dose levels. There were no effects of mesna on 3-methylhistidine, a marker of protein breakdown.
Does medial tourism promote growth in healthcare sector?
Authors: Gholipour Hassan F. , Esfandiar Kourosh
Published: June 2024

The purpose of this study is to investigate the effect of medical tourism revenues on the growth of healthcare sector across 49 emerging and developed economies from 2008 to 2022. Using panel GMM and PMG/ARDL estimation methods, the results show that higher levels of medical tourism revenues promote growth in the healthcare sector. This finding remains robust across different sample periods, alternative measure of healthcare sector performance, and model specifications.
The potential contribution of aberrant cathepsin K expression to gastric cancer pathogenesis
Authors: Feng Zhijun , Gao Lina , Lu Yapeng , He Xiaodong , Xie Jianqin
Published: June 2024

The role of cathepsin K (CTSK) expression in the pathogenesis and progression of gastric cancer (GC) remains unclear. Hence, the primary objective of this study is to elucidate the precise expression and biological role of CTSK in GC by employing a combination of bioinformatics analysis and in vitro experiments. Our findings indicated a significant upregulation of CTSK in GC. The bioinformatics analysis revealed that GC patients with a high level of CTSK expression exhibited enrichment of hallmark gene sets associated with angiogenesis, epithelial–mesenchymal transition (EMT), inflammatory response, KRAS signaling up, TNFα signaling via KFκB, IL2-STAT5 signaling, and IL6-JAK-STAT3 signaling. Additionally, these patients demonstrated elevated levels of M2-macrophage infiltration, which was also correlated with a poorer prognosis. The results of in vitro experiments provided confirmation that the over-expression of CTSK leads to an increase in the proliferative and invasive abilities of GC cells. However, further evaluation was necessary to determine the impact of CTSK on the migration capability of these cells. Our findings suggested that CTSK has the potential to facilitate the initiation and progression of GC by augmenting the invasive capacity of GC cells, engaging in tumor-associated EMT, and fostering the establishment of an immunosuppressive tumor microenvironment (TME).
Lycorine attenuated proliferation and induced apoptosis on imatinib-resistant K562 cell by inhibiting autophagy
Authors: Bai Jun , Feng Zuxi , Chen Yaqiong , Li Yanhong , Zhang Liansheng , Li Lijuan
Published: June 2024

Background

Tyrosine kinase inhibitor (TKI) resistance is a significant factor exacerbating the burden on chronic myeloid leukemia (CML) patients and impacting clinical efficacy. The main goal is to offer new insights into overcoming drug resistance in treating CML.

Methods

Imatinib (IM) resistant K562/IM cells were generated using gradient induction. Responses to IM, lycorine, and autophagy modulators were assessed using CCK-8. Protein expression of Beclin-1, Atg5, LC3, Caspase-3, P62, Bax, Bcl-2, and P-gp was detected using Western blot. Lycorine-induced apoptosis and cell cycle changes were evaluated through flow cytometry, while autophagy alterations were detected using monodansylcadaverine (MDC) staining. In the K562/IM mice model, non-obese diabetic severe combined immunodeficent (NOD-SCID) mice were subcutaneously inoculated with K562/IM cells. After 17 days of lycorine injection, assessments included tumor size, hematoxylin–eosin (HE) staining, and Ki67 expression.

Results

After 72 h of IM treatment, K562/IM cells showed a 55.86-fold increase in drug resistance compared to K562 cells. Lycorine treatment for 24 h inhibited cell proliferation and induced G0/G1 phase cell cycle arrest and apoptosis in both K562 and K562/IM cells. MDC staining indicated reduced autophagy in K562/IM cells, mitigated by lycorine. In vivo experiments demonstrated reduced tumor size and Ki67 proliferation index in the lycorine treatment group (K562+L, K562/IM+L) compared to the control group, particularly in the drug-resistant group. However, no significant change in Ki67 was observed in the K562 group after lycorine treatment.

Conclusion

In summary, K562/IM cells displayed heightened autophagy levels compared to K562 cells. Lycorine effectively impeded the proliferation of K562/IM cells through diverse mechanisms, including reduced autophagy, enhanced apoptosis, and induced cell cycle arrest.
Proteomic profiling of human dental enamel affected by molar incisor hypomineralisation of different clinical severity grades: an in vitro study
Authors: Rexhaj F. , Sabel N. , Robertson A. , Lundgren T.
Published: June 2024

Purpose

The aim of this study was to explore the potential to profile and distinguish varying clinical severity grades of MIH, compared to normal enamel, using proteomics.

Methods

Liquid chromatography–mass spectrometry analyses were conducted on enamel samples of extracted teeth, from 11 children and adolescents, spanning an age range of 6–18 years. Enamel powder samples were collected from extracted, third molars (n = 3) and first permanent molars diagnosed with MIH (n = 8). The MIH tooth samples were categorized into subgroups based on clinical severity grade. The data were statistically analyzed using ANOVA and Welch’s t test.

Results

Teeth affected by MIH exhibited a diverse array of proteins, each with different functions related to dental enamel, distinguishing them from their normal enamel counterparts. The application of microdissection combined with LC–MS techniques has revealed the potential to discern unique proteomic profiles among MIH-affected teeth, characterized by varying clinical severity grades. Both analyzed MIH groups displayed consistent trends in the presentation of biological processes, including underabundance of proteins primarily associated with cell organization and biogenesis. Furthermore, proteins linked to cell death were overabundant in both MIH groups.

Conclusion

Proteomics enabled the detection and differentiation of various proteins across different clinical severity grades of MIH.
Erdos: A Novel Blockchain Consensus Algorithm with Equitable Node Selection and Deterministic Block Finalization
Authors: Sello Buti , Yong Jianming , Tao Xiaohui
Published: June 2024

The introduction of blockchain technology has brought about significant transformation in the realm of digital transactions, providing a secure and transparent platform for peer-to-peer interactions that cannot be tampered with. The decentralised and distributed nature of blockchains guarantees the integrity and authenticity of the data, eliminating the need for intermediaries. The applications of this technology are not limited to the financial sector, but extend to various areas, such as supply chain management, identity verification, and governance. At the core of these blockchains is the consensus mechanism, which plays a crucial role in ensuring the reliability and integrity of a system. Consensus mechanisms are essential for achieving an agreement amongst network participants regarding the validity of transactions and the order in which they are recorded on the blockchain. By incorporating consensus mechanisms, blockchains ensure that all honest nodes in the network reach a consensus on whether to accept or reject a block, based on predefined rules and criteria. The aim of this study is to introduce a novel consensus mechanism named Erdos, which seeks to address the shortcomings of existing consensus algorithms, such as the Proof of Work and Proof of Stake. Erdos emphasises security, decentralisation, and fairness. One notable feature of this mechanism is its equitable node-selection algorithm, which ensures equal opportunities for all nodes to engage in block creation and validation. In addition, Erdos implements a deterministic block finalisation process that guarantees the integrity and authenticity of the blockchain. The main contribution of this research lies in its innovative approach to deterministic block finalisation, which effectively mitigates the various security risks associated with blockchain systems.
Geoelectric analysis for groundwater potential assessment and aquifer protection in a part of Shango, North-Central Nigeria
Authors: Ejepu J. S. , Jimoh M. O. , Abdullahi S. , Abdulfatai I. A. , Musa S. T. , George N. J.
Published: June 2024

Groundwater is vital for sustainable development, and this study addresses potable water challenges in Shango, North-Central Nigeria. The main goal is to identify optimal sites for new wells and boreholes, utilizing geological and geo-electrical attributes from existing boreholes and wells. Vertical Electrical Sounding (VES) assessed groundwater potential, aquifer protection, and overburden corrosivity. Sixteen VES stations were probed using Schlumberger array with a maximum current electrode spacing (AB/2) of 200 m using a resistivity meter. The data were interpreted using an automatic computer inversion program, IPI2WIN. The VES results revealed five subsurface geo-electric units, with depths to the aquifer ranging from 58 to 68 m, each exhibiting distinct characteristics contributing to the lithological variability of the research area. Hydraulic conductivity ranged from 0.465 to 0.534 m/day, while transmissivity varied from 9.589 m2/day to 26.029 m2/day across different VES points. Regions exhibiting thick layers and low resistivity values indicate high longitudinal conductivity. Furthermore, areas with low protective capacity are susceptible to the risks of pollution and contamination stemming from leaks and waste sites. The study revealed that all VES points are in practically non-corrosive zones, making them suitable for burying underground tanks with extremely low deterioration rates. Based on geoelectrical characteristics, the study area was divided into three groundwater potential zones: low, medium, and high. These findings provide valuable insights into the groundwater potential and protective capacity of the Shango area, while emphasizing on the vulnerability of these regions and highlighting the pressing need for appropriate preventive measures to safeguard against potential environmental hazards.
Delving into river health: unveiling microplastic intrusion and heavy metal contamination in freshwater
Authors: Bhat Mansoor Ahmad , Janaszek Agata
Published: June 2024

The persistent use of plastics in chemical and industrial procedures has resulted in the contamination of the environment and human health via microplastics (MPs). This study investigates heavy metals, MP, pH, conductivity, and turbidity levels in the Nida River in Poland. The Nida River exhibited the existence of diverse coloured MPs in several physical forms, including fibres, fragments, pellets, and foams. Differences in the number of MPs were noted at five selected locations, with values ranging from 215 to 280 MPs per litre. The mean number of MPs observed was 245 ± 21 per litre. The study of water samples using a scanning electron microscope indicates the existence of various MPs. The morphological study of these MPs revealed patterns of degradation. The energy-dispersive X-ray examination indicates the existence of several elements, such as carbon, nitrogen, oxygen, sodium, magnesium, aluminium, silicon, phosphorus, and others. The water exhibited fluctuations in its levels of heavy metal content. The average zinc concentration in all samples was 96.86 ± 40.25 μg/L, which was the highest. It was followed by Pb 37.6 ± 31.9 μg/L concentration. The turbidity measurement was recorded as 46.38 ± 22.54, the pH level was 7.078 ± 0.33, and the conductivity value was determined to be 1338.8 ± 39.64. The HQ and HI values for adults and children in all age groups were less than one. The carcinogenic excess lifetime cancer risk (ELCR) exceeds the threshold value in most water samples. This study aims to fill the existing gap in understanding the precise measurement of MPs and heavy metals in freshwater sources in Poland. Health risk evaluations are the first step in developing pollution management, control, and water quality standards.

Graphical Abstract
Reinventing Insolvency Law in Emerging Economies
Authors: Gurrea-Martínez Aurelio
Published: June 2024

This book explains how and why insolvency law in emerging economies needs to be reinvented. It starts by examining the importance of insolvency law for the promotion of economic growth as well as the similarities and divergences in the design of insolvency law around the world. The central thesis of the book is that insolvency law in emerging economies fails to serve as a catalyst for growth. It is argued that this failure is mainly due to the design of an insolvency legislation that is not tailored to the market and institutional environment generally existing in emerging economies. The book also provides a critical analysis of the design of insolvency law in many advanced economies where the insolvency system has proven to be unattractive for debtors, creditors or both. Therefore, in addition to suggesting a new insolvency framework for emerging economies, this book ultimately invites readers to rethink insolvency law.
A Magnetic Low May Have Paved the Way for Complex Life
Authors: Bolakhe Saugat
Published: June 2024

Multicellular life blossomed when Earth’s magnetic field was at an all-time low.