bluuebunny/crossref_metadata_2025 huggingface dataset:
Ambient Air Pollution Exposure and Outcomes in Patients Receiving Lung Transplant
Authors: Amubieya Olawale , Weigt Sam , Shino Michael Y. , Jackson Nicholas J. , Belperio John , Ong Michael K. , Norris Keith
Published: October 2024

Importance

Elevated ambient fine particulate matter (PM2.5) air pollution exposure has been associated with poor health outcomes across several domains, but its associated outcomes among lung transplant recipients are poorly understood.

Objective

To investigate whether greater PM2.5 exposure at the zip code of residence is associated with a higher hazard for mortality and graft failure in patients with lung transplants.

Design, Setting, and Participants

This retrospective cohort study used panel data provided by the United Network for Organ Sharing, which includes patients receiving transplants across all active US lung transplant programs. Adult patients who received lung transplants between May 2005 and December 2016 were included, with a last follow-up of September 10, 2020. Data were analyzed from September 2022 to May 2023.

Exposure

Zip code–level annual PM2.5 exposure was constructed using previously published North American estimates.

Main Outcomes and Measures

The primary outcome was time to death or lung allograft failure after lung transplant. A gamma shared frailty Cox proportional hazards model was used to produce unadjusted and adjusted hazard ratios (HRs) to estimate the association of zip code PM2.5 exposure at the time of transplant with graft failure or mortality.

Results

Among 18 265 lung transplant recipients (mean [SD] age, 55.3 [13.2] years; 7328 female [40.2%]), the resident zip code’s annual PM2.5 exposure level was greater than or equal to the Environmental Protection Agency (EPA) standard of 12μg/m3 for 1790 patients (9.8%) and less than the standard for 16 475 patients (90.2%). In unadjusted analysis, median graft survival was 4.87 years (95% CI, 4.57-5.23 years) for recipients living in high PM2.5 areas and 5.84 years (95% CI, 5.71-5.96 years) for recipients in the low PM2.5 group. Having an annual PM2.5 exposure level greater than or equal to the EPA standard 12 μg/m3 was associated with an increase in the hazard of death or graft failure (HR, 1.11; 95% CI, 1.05-1.18; P < .001) in the unadjusted analysis and after adjusting for covariates (HR, 1.08; 95% CI, 1.01-1.15; P = .02). Each 1 μg/m3 increase in exposure was associated with an increase in the hazard of death or graft failure (adjusted HR, 1.01; 95% CI, 1.00-1.02; P = .004) when treating PM2.5 exposure as a continuous variable.

Conclusions and Relevance

In this study, elevated zip code–level ambient PM2.5 exposure was associated with an increased hazard of death or graft failure in lung transplant recipients. Further study is needed to better understand this association, which may help guide risk modification strategies at individual and population levels.
Handheld Cellphone Use and Risky Driving in Adolescents
Authors: McDonald Catherine C. , Rix Kevin , Ebert Jeffrey P. , Aryal Subhash , Xiong Ruiying , Wiebe Douglas J. , Delgado M. Kit
Published: October 2024

Importance

Handheld cellphone use while driving is associated with increased motor vehicle crash risk among adolescents.

Objective

To examine the association of handheld cellphone use while driving with kinematic risky driving (KRD) events—hard braking and rapid acceleration—in adolescent drivers.

Design, Setting, Participants

Adolescents aged 16.50 to 17.99 years licensed 365 days or less in Pennsylvania were eligible to participate in this cross-sectional study. Enrollment occurred from July 29, 2021, to June 6, 2022. Participants downloaded a smartphone telematics cellphone app to record driving data for 60 days.

Exposures

Trip characteristics, including frequency, length, and duration; presence of speeding; frequency and duration of handheld cellphone use; time of day; and presence of precipitation.

Main Outcomes and Measures

Kinematic risky driving events per 100 miles driven. Zero-inflated Poisson regression models examined whether individual characteristics and trip characteristics were associated with KRD. Incidence rate ratios were computed.

Results

Of 405 adolescents who responded to recruitment, 151 enrolled, 140 completed study procedures, and 119 with 12 360 trips were included in the analytic sample (60 female participants [50.4%]; mean [SD] age, 17.2 [0.4] years). Adolescents drove a mean (SD) of 103.8 (65.7) trips, 565.0 (487.3) miles, and 25.1 (19.3) hours. Adolescents had minimal night trips (1.5% [192]), and few trips with precipitation present (9.0% [1097]). Speeding occurred in 43.9% (5428) of the trips and handheld cellphone use occurred in 34.1% (4214) of the trips. Kinematic risky driving events occurred in 10.9% (1358) of the trips at a rate of 2.65 per 100 miles. In adjusted models, increased KRD events were associated with handheld cellphone use (incidence rate ratio [IRR], 2.62; 95% CI, 1.53-4.48), speeding (IRR, 2.12; 95% CI, 1.06-4.26), and minutes driving (IRR, 1.02; 95% CI, 1.01-1.02). Trips at night, precipitation presence, licensure for less than 6 months, and sex were not associated with increased KRD events.

Conclusions

In this cross-sectional study of adolescent drivers, trips with handheld cellphone use and speeding were associated with higher rates of KRD, while individual characteristics were not. The findings suggest that smartphone telematics apps provide an opportunity to observe behaviors as well as surveil changes due to intervention efforts.
Large Retinal Cystoid Abnormality on Ultra-Widefield Swept-Source OCT
Authors: Zhang Yue , Liu Qiang , Yu Xiaobing
Published: October 2024

This case report discusses a diagnosis of retinal cystoid abnormality and retinal detachment on ultra-widefield optical coherence tomography (OCT) in the setting of fluctuating visual loss in the right eye.
Acute Transient Cataract Associated With 5-Fluorouracil
Authors: Roh Yu Jin , Lee Eun Ji , Kim Tae-Woo
Published: October 2024

This case report discusses a diagnosis of transient cataract in the setting of 5-fluorouracil injection to treat a fibrotic trabeculectomy bleb.
Virus‐Assembled Biofunctional Microarrays with Hierarchical 3D Nano‐Reticular Network
Authors: Tian Lei , Khan Shadman , Shakeri Amid , Jackson Kyle , Saif Ahmed T. , Bayat Fereshteh , He Leon , Gu Jimmy , Li Yingfu , Didar Tohid F. , Hosseinidoust Zeinab
Published: October 2024

Three‐dimensional (3D) hierarchical wrinkled materials built with biological entities have so far remained exclusive to nature. Herein, multiscale functional ultraporous 3D bio‐networks of bioprinted phage‐built wrinkled microarrays are created through establishing a universal heat‐ and solvent‐independent substrate‐shrinkage method induced by high‐pressure carbon dioxide (HPCD). This method results in diverse wrinkled patterns on soft materials and is particularly powerful for solvent‐ and heat‐sensitive biomaterials, for which other methods have failed. The phage nanofilaments (7 nm width) self‐assemble into orderly‐aligned submicron bundles (100 nm width), which crimp into tunable microscale wrinkles (0.7–5.0 µm width) on size‐controllable micro‐arrays (200–600 µm width) exhibiting a four‐level hierarchical nano‐reticular structure. The HPCD method also protects the bioactivity of biorecognition molecules loaded into the microarrays, leading to the design of bacteria‐sensing chips, made with in‐house deoxyribozyme‐loaded 3D phage microarrays. The developed bacteria‐sensing chips achieve a limit of detection that is 100 × more sensitive with greater reproducibility compared to two‐dimensional (2D) microdot arrays and correctly identify Legionella pneumophila in contaminated water samples collected from industrial cooling towers, highlighting phage‐built wrinkled networks as a platform for bottom‐up assembly of biological building blocks into biofunctional material.
Hybrid Antibacterial Surfaces: Combining Laser‐Induced Periodic Surface Structures with Polydopamine‐Chitosan‐Silver Nanoparticle Nanocomposite Coating
Authors: Wang Yimeng , Dong Yuhang , Quan Yuhua , Wackerow Stefan , Abdolvand Amin , Zolotovskaya Svetlana A. , Zhao Qi
Published: October 2024

Bacterial biofilm‐associated infections are a persistent and growing problem, further exacerbated by the rapid development of antibiotic‐resistant bacterial strains. Antibacterial surfaces hold great potential for controlling the survival, growth, and transmission of bacterial pathogens. This study demonstrates the synergetic integration of laser‐assisted topographical surface modification with coating solutions to simultaneously engage both chemical and nano‐/micro‐topography‐sensitive bacterial attachment mechanisms. The developed mechano‐chemo bactericidal surface combines laser‐induced periodic surface structures (LIPSS) on titanium (Ti) with a polydopamine‐chitosan‐silver nanoparticles (PCA) composite coating. The antibacterial performance of this hybrid surface against Gram‐negative Escherichia coli (E. coli) and Gram‐positive Staphylococcus aureus (S. aureus) exceeds the benchmark performance achieved by either surface modification approach alone. The hybrid surface demonstrates superior resistance to biofilm formation, offering a viable route for large‐scale production of antimicrobial surfaces with enhanced functionality and superior long‐term performance.
Functionalization of cellulose pentamine as a promising nano‐amorphous sorbent for Zr(IV) and Hf(IV) ions recovery
Authors: Mubark Amal E. , Falila Nagwa I. , Mohamed Basma T. , Salem Hend M.
Published: October 2024

Due to the rising worldwide need for commercial zirconium and hafnium metals, various research studies have been conducted to investigate their extraction from ores and recovery from other waste products. By chorinating cellulose and then aminating it with tetraethylene pentamine, a cellulose‐tetraethylene pentamine (Cell‐TEPA) nanosorbent was synthesized, which resulted in active groups responsible for binding processes with the appropriate metal ions using a straightforward approach. The composition, chemical characteristics, and physical attributes of the Cell‐TEPA nanosorbent were comprehensively examined using a range of equipment, such as X‐ray diffraction (XRD), scanning electron microscope–energy dispersive X‐ray analysis (SEM–EDX), Fourier‐transform infrared spectroscopy (FT‐IR), Brunauer–Emmett–Teller (BET), and thermal gravimetric analysis (TGA). When bound to the Cell‐TEPA nanosorbent, Zr(IV) and Hf(IV) exhibited the highest absorption capacities of 70.4 and 38.2 mg/g, respectively. The most favourable sorption conditions were achieved with a feed solution pH of 1.5, a stirring period of 45 min, a metal ion concentration of 100 mg/L, and room temperature (25 ± 2°C). The adsorption data were consistent with both the Langmuir isothermal model and the pseudo‐2nd‐order reaction model. The Cell‐TEPA nanosorbent effectively extracted zirconium and hafnium ions from leach liquors derived from Wadi Rahba ore sample and Abu Khashaba concentrate sample, demonstrating their potential for future applications.
Accessibility
Authors: Lyerly Eric
Published: October 2024

An overview of the key topics faced by disability services providers with citations to noteworthy cases, statutes, regulations, and additional sources.
Bioinformatics analysis of G protein subunit gamma transduction protein 2‐autophagy axis in CD11b+ dendritic cells as a potential regulator to skew airway neutrophilic inflammation in asthma endotypes
Authors: Ji Xiaoying , Zhou Yaoliang , He Shendong , Chen Hongda , Zhang Xianming , Chen Zhifeng , Cai Jinwen
Published: October 2024

Background

Asthma is a heterogeneous inflammatory disease with two main clinical endotypes: type 2 (T2) high and low asthma. The plasticity and autophagy in dendritic cells (DCs) influence T helper (Th)2 or Th17 differentiation to regulate asthma endotypes. Enhanced autophagy in DCs fosters Th2 differentiation in allergic environments, while reduced autophagy favors Th17 cell differentiation in sensitized and infected environments. Autophagy regulation in DCs involves interaction with various pathways like G protein‐coupled receptor (GPCR), mammalian target of rapamycin (mTOR), or phosphoinositide 3‐kinase (PI3K) pathway. However, specific molecules within DCs influencing asthma endotypes remain unclear.

Methods

Gene expression data series (GSE) 64896, 6858, 2276, and 55247 were obtained from gene expression omnibus (GEO) database. Differentially expressed genes (DEGs) between CD103+ and CD11b+ DCs after induction by ovalbumin (OVA) and lipopolysaccharide (LPS) were analyzed using GEO2R. DEGs were examined through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein–protein interaction (PPI) analyses. The hub gene network was construct with STRING database and Cytoscape. Autophagy differences in DCs and the selected hub gene in GSE6858, GSE2276, and GSE55247 were evaluated using student t tests.

Results

Our analysis identified 635 upregulated and 360 downregulated genes in CD11b+ DCs, compared to CD103+ DCs. These DEGs were associated with “PI3K‐AKT signaling pathway,” “Ras signaling pathway,” and so forth. Thirty‐five hub genes were identified, in which G protein subunit gamma transduction protein 2 (Gngt2) in CD11b+ DCs exhibited a relatively specific increase in expression associated with autophagy defects under the induction environment similar to T2 low asthma model. No significant difference was found in lung Gngt2 expression between T2 high asthma model and control group.

Conclusion

Our analysis suggested Gngt2 acted as an adapter molecule that inhibited autophagy, promoting Th17‐mediated airway inflammation via the GPCR pathway in a T2 low asthma mice model. Targeting this pathway provides new asthma treatment strategies in preclinical research.
EMP1 knockdown mitigated high glucose‐induced pyroptosis and oxidative stress in rat H9c2 cardiomyocytes by inhibiting the RAS/RAF/MAPK signaling pathway
Authors: Han Ying , Gong Jin , Pan Min , Fang Zhoufei , Ou Xiaowen , Cai Wenqin , Peng Xiane
Published: October 2024

The purpose of this study was to investigate the mechanism of EMP1 action in high glucose (HG)‐induced H9c2 cardiac cell pyroptosis and oxidative injury. Rat cardiomyocytes H9c2 were exposed to 33 mM glucose for 24, 48, or 72 h to induce cytotoxicity. EMP1‐siRNA, NLRP3 agonist Nigericin, and pcNDA‐RAS were used to treat H9c2 cells under HG conditions. Cell Counting Kit (CCK)‐8 assay showed that cell proliferation was decreased following HG induction, which was rescued by EMP1 knockdown. Our results also suggested that EMP1 siRNA transfection significantly decreased the apoptosis and pyroptosis of HG‐induced cells, as indicated by the reduction of NLRP3 IL‐1β, ASC, GSDMD, cleaved‐caspase1 and cleaved‐caspase3 levels in HG‐induced H9c2 cells. In addition, EMP1 knockdown alleviated HG‐induced mitochondrial damage and oxidative stress in H9c2 cells. NLRP3 activation reversed the inhibitory effects of EMP1 knockdown on pyroptosis and oxidative stress in HG‐induced H9c2 cells. Mechanistically, we found that EMP1 knockdown suppressed the RAS/RAF/MAPK signaling pathway in HG‐induced H9c2 cells. RAS overexpression blocked the protective effect of EMP1 knockdown on HG‐induced H9c2 cell apoptosis, pyroptosis, and oxidative injury. Our findings suggest that EMP1 knockdown treatment might provide a novel therapy for diabetic cardiomyopathy.
miR‐195‐5p inhibits cisplatin resistance in lung adenocarcinoma by regulating DNA damage via targeting E2F7
Authors: Wu Huanghui , Zheng Biaolong
Published: October 2024

Lung adenocarcinoma (LUAD) emerges as one of the most lethal malignant tumors worldwide. Platinum‐based combination chemotherapy remains one of the main methods for patients with advanced LUAD. Due to the resistance, the effect of this chemotherapy was not satisfactory. Therefore, studying the mechanism of cisplatin (DDP) resistance is essential for promoting the effect of this therapeutic strategy. Therefore, this work sought to probe the impact of E2F Transcription Factor 7 (E2F7) on LUAD resistance and the molecular regulatory mechanism. The mRNA expression level of the target gene E2F7 in LUAD was predicted by bioinformatics analysis, and regulatory miRNA upstream of the target gene was identified. The mRNA and protein expression of E2F7 in LUAD cells was detected through quantitative reverse transcriptase polymerase chain reaction (qRT‐PCR) and Western blot, respectively. The expression of miR‐195‐5p in LUAD cells was measured via qRT‐PCR. E2F7 high and low expression groups underwent enrichment analysis by utilizing Gene Set Enrichment Analysis software. The targeting relationship of miR‐195‐5p and E2F7 was validated by conducting a dual‐luciferase reporter assay. The cell viability was tested through cell counting kit‐8. The cell cycle was examined by flow cytometry. DNA damage level was determined via Comet assay and Western blot assay. The findings indicated that the mRNA and protein levels of E2F7 were high in LUAD. MiR‐195‐5p was the regulatory miRNA upstream of E2F7, and lowly expressed in LUAD. The cell experiments suggested that E2F7 advanced the DDP resistance of LUAD cells by repressing DNA damage. Finally, the rescue assay manifested that miR‐195‐5p overexpression could abate inhibition of E2F7 overexpression on the DNA damage and the DDP sensitivity of LUAD cells. MiR‐195‐5p raised the DDP sensitivity of LUAD cells by advancing the DNA damage in LUAD cells via inhibition of E2F7.
Exposure‐Efficacy Analysis and Dopamine D2 Receptor Occupancy in Adults with Schizophrenia after Treatment with the Monthly Intramuscular Injectable Risperidone ISM
Authors: Lindauer Andreas , Snoeck Eric , Laveille Christian , Ayani Ignacio , de Monasterioguren Lourdes Ochoa Díaz , Almendros Marcos , Martínez‐González Javier , Anta Lourdes , Gutierro Ibón
Published: October 2024

Dopamine D2 receptor occupancy (D2RO) significantly influences the clinical effectiveness and safety of many antipsychotic drugs. Maintaining a D2RO range of 65%–80% provides the best antipsychotic effects while minimizing adverse reactions. Data from a Phase III trial were used to establish an exposure–response relationship for monthly intramuscular Risperidone ISM (75 and 100 mg) or placebo administered to adults with schizophrenia. Pharmacodynamic analysis was based on an Emax model for Positive and Negative Syndrome Scale (PANSS) developed in NONMEM. Plasma concentrations of the active moiety were derived using a previously developed population pharmacokinetic model, which was used for D2RO simulations in conjunction with a published Emax model. The optimal D2RO range (65%–80%) was reached for the median within hours following the first injection of both Risperidone ISM doses. At steady state, median D2RO for both doses remained above 65% throughout the 28‐day dosing period and demonstrated lower variability than oral risperidone. PANSS response did not differ significantly between dose groups, most likely because active moiety concentrations had already reached the plateau of the concentration–response relationship. The pharmacokinetic/pharmacodynamic analysis showed a profound placebo effect (−11.7%), and an additional maximal drug effect (−6.6%) resulting in a total PANSS improvement over time of −18.3%. Pharmacokinetic/pharmacodynamic modeling quantified a PANSS improvement over time after Risperidone ISM administration. The response was not significantly different in either dose group, likely because D2RO was already above the proposed efficacy threshold (65%) within 1 h after the first Risperidone ISM injection and remained above this level following repeated administrations.
In‐situ fabrication of poly‐l‐lactide & its application as a glass fiber polymer composites using resin transfer molding
Authors: Kim Seon‐Ju , Pandey Kalpana , Poddar Deepak , Yoo Hyeong Min
Published: October 2024

A detailed investigation was employed on the manufacturing process of Glass Fiber (GF) reinforced poly‐L‐lactide (PLLA) composites (GFRP) during in‐situ PLLA polymerization using Resin Transfer Molding (RTM). The lower viscosity of lactide, in comparison to PLLA, led to a strong interaction between PLLA and GF as a result of improved penetration into the fiber matrix, resulting in a high conversion rate of 100% for GFRP and 91.9% for PLLA. GF incorporation into the composite material resulted in an improved crystallinity of 55.65% for GFRP, where PLLA showed crystallinity of 36.5%. A GFRP composite with exceptional mechanical properties, including 122.3 MPa tensile strength and 4.485 GPa modulus, was achieved. Both surface and bulk erosion were seen during the breakdown of these composites. These composites seem to be a viable substitute for metallic implants in biological applications.

Highlights

In situ, resin transfer molding of poly‐l‐lactide and GF composite.

Higher volume fraction such as 40% w/v loading of GF into composites.

1% conversion of GFRP is achieved.

GFRP shows the machinal strength of 122 MPa and harness of 4.2 GPa.

Biocompatibility of GFRP composites in body stimulated conditions.
Neurodevelopmental outcomes in children prenatally exposed to opioid maintenance treatment: A population‐based study
Authors: Hasan Mennatullah , Meador Kimford J. , Brothers Todd N. , Wang Shuang , Lewkowitz Adam K. , Ward Kristina E. , Slaughter Jonathan L. , Zhang Yichi , Wen Xuerong
Published: October 2024

Background and Objectives

Opioid maintenance treatment (OMT), with methadone or buprenorphine, is a key approach for managing opioid use disorder (OUD) during pregnancy. Despite buprenorphine's superior short‐term outcomes, its long‐term effects remain understudied. This study aims to evaluate the effects of prenatal OMT exposure on the incidence of childhood neurodevelopmental disorders (NDDs) considering timing effect.

Methods

A retrospective cohort study using Rhode Island Medicaid data linked to vital statistics from 2008 to 2018 was conducted. The study included pregnancies having live birth from 2008 to 2016 with continuous Medicaid insurance and OUD diagnosis within 3 months preceding conception until delivery. At least one buprenorphine dispensing or a claim of methadone was required for exposure definition. Exposure was evaluated during early (0–90 days) or late (>90 days) gestation, or at any pregnancy phase. NDDs, including autism, attention‐deficit/hyperactivity disorder (ADHD), learning disabilities, speech/language disorders, developmental coordination disorder, intellectual disability, and behavioral disorders, were identified using validated algorithms. Applying Cox proportional‐hazard models with propensity score overlap weighting, adjusted hazard ratios (aHR) were calculated, mitigating potential confounders. Children were followed up from birth until NDD diagnosis, disenrollment, or study end.

Results

Of 416 mother–child dyads with OUD, 40% used methadone and 20% had buprenorphine exposure during pregnancy. NDDs were observed in 36% of children with early methadone exposure compared to 17% in the early buprenorphine exposed group (aHR: 2.75; 95% confidence interval [CI]: 1.42–5.35). Further comparison to late buprenorphine exposure, late methadone exposure was associated with higher NDD risk (aHR: 2.05; 95% CI: 1.09–3.86). Compared to unexposed group, children exposed to methadone during early and late periods showed higher NDD incidences (aHR: 2.33; 95% CI: 1.51–3.60 and aHR: 2.42; 95% CI: 1.54–3.80, respectively).

Discussion

The study suggests that buprenorphine is a good treatment option for OUD during pregnancy due to minimal long‐term neurodevelopmental impacts on children. However, further extensive research is necessary to rule‐out potential confounding.
Empowering the next‐generation climate scientists: insights from the 2023 Forecasters' WEB exchange program/hackathon at KNUST, Ghana
Authors: Aryee J. N. A. , Mensah C. , Ayitah D. E. , Adjei A. D. , Forson K. P. , Tanko A. A. , Asenso S. , Nketsiah D. , Okofo Dartey E. , Prempeh N. A.
Published: October 2024

The Forecasters’ WEB of the Kwame Nkrumah University of Science and Technology and University of Energy and Natural Resources collaborated on a pioneering exchange program/hackathon to address climate change challenges. Aimed at educating students, the program covered forecasting techniques, scientific programming and featured mentor sessions. Participants analysed historical climate change in Africa, revealing temperature increases and no clear precipitation patterns. The program showcased successful outcomes, emphasizing the importance of skill development and collaboration. The paper highlights the program strengths, limitations and outcomes, emphasizing its role in cultivating next generation of climate scientists.
Above‐ground nest locations support key life stages and group behaviours in Eurasian badger territories
Authors: McCaskill Michael , Rainey Elaine , Farnan Lesley , McCafferty Dominic J. , White Stewart
Published: October 2024

Although the Eurasian badger Meles meles is well known for occupying underground setts, badgers also use nests above ground. There is limited research as to how these above‐ground nests function within a badger territory and which behaviours and life stages they provide for social groups. This project investigated the use of above‐ground nests within known badger territories, taking into consideration when and how they are used by the group, as well as identifying where nests are located and where they are likely to be found in relation to other territory features. We found that nests were located closer to habitat boundaries than main sett or satellite locations, and latrines. The probability of a badger using a nest was greater at night, with nests supporting important behaviours such as mating and social interactions during the hours of darkness. Mating and grooming were found to decrease the further nests were from main sett locations, whereas territorial behaviours in nests were found to decrease the further nests were from habitat edges. This study provides new understanding of above‐ground badger behaviour and use of nests and their function within badger territories, which may have implications for current badger legislation and best‐practice survey guidelines.
Therapieoptionen bei angeborenen Stoffwechselstörungen
Authors: Zöggeler Thomas , Höller Alexander , Margreitter Julian , Bachmann Magdalena , Schönlaub Anna Katharina , Jörg-Streller Monika , Karall Daniela , Scholl-Bürgi Sabine
Published: October 2024

Mehr als 1450 angeborene Stoffwechselstörungen sind bekannt. Von ihnen stellen genetisch determinierte Enzymdefekte in Diagnostik und Therapie oft eine große Herausforderung dar. Die Diagnostik erfolgt auf 3 Ebenen: biochemisch, enzymatisch und genetisch. Ebenso setzen verfügbare Therapieoptionen an diesen 3 Ebenen an: auf der biochemischen (Substrat‑)Ebene in Form einer Modifikation der Substrate (meist als Ernährungstherapie, „Diät“), der Enzymebene mit Ersatz oder Stabilisierung der defekten Enzyme und der Genebene als Genersatztherapie aktuell in Form einer Organ- oder Stammzelltransplantation, in Zukunft auch z. B. auf Vektoren basierend. Circa 20 % der angeborenen Stoffwechselstörungen können in irgendeiner Form mit einer Ernährungstherapie behandelt werden. Ziel der Ernährungstherapie ist, die Stoffwechselstörung nicht zur Stoffwechselkrankheit werden zu lassen. Ebenso ist es Ziel, eine Enzym- bzw. Gentherapie rechtzeitig zu beginnen, um irreversible Schäden zu vermeiden.
Effect of cenospheres on the proprieties of plain concrete exposed to elevated temperature
Authors: Gabriela Rutkowska , Paweł Ogrodnik , Aleksandra Powęzka , Mariusz Żółtowski , Filip Chyliński , Karolina Kaszewska
Published: October 2024

The main objective of the study was to determine the effect of the use of cenospheres for C30/37 class concretes used in construction and road construction. As part of the research, four concrete mixtures were designed: three with the addition of cenospheres and one reference mixture, without the additive. In the three modified mixtures, 20, 40 and 60% of fine aggregate were replaced by cenospheres, respectively. Selected features of the mixtures were determined—consistency and density, as well as the strength properties of concrete. Strength tests were carried out after 28 and 56 days of maturation. Experimental tests of concrete after initial thermal treatment were also carried out at three selected temperatures: 300, 500 and 700 °C, with loading times ranging from 60 to 180 min. These times were selected in such a way that the samples could be heated in their entire volume. A separate group of experimental studies was microstructure studies, the aim of which was to assess the changes occurring in concrete under the influence of high temperatures and to try to justify why CS-I concrete containing cenospheres in the amount of 20% of concrete subjected to annealing at 300 °C has a higher compressive strength than the corresponding reference concrete. The negative influence of cenospheres on the strength of concrete after initial thermal treatment was unequivocally demonstrated. An increase in the amount of cenospheres causes a decrease in compressive strength. A similar negative relationship was also demonstrated in the case of non-heat-treated samples.

Graphical Abstract
Classifying the content of online notepad services using active learning
Authors: Al-Nabki Mhd Wesam , Fidalgo Eduardo , Alegre Enrique , Delany Sarah Jane , Jáñez-Martino Francisco
Published: October 2024

Pastebin is an online notepad service to share text anonymously. However, it could be misused to propagate suspicious or even illegal activities, like leaking sensitive information or sharing hyperlinks to child sexual abuse material. Due to the high rate of daily upload pastes, manual inspection of this material is not feasible. Conversely, an automatic classifier could identify such activities with little or no human intervention. However, a supervised model may require a significant number of training samples and have to handle distinct text typologies presented in Pastebin. This paper presents a classification approach composed of three cascading supervised classifiers that use Active Learning to select and label the most informative samples from Pastebin. The modularity of the proposed design allows each classifier to adapt to a specific text typology. The first classifier determines whether the text is a code snippet, and the second is to identify whether it is readable. The third classification level is twofold: (i) a binary classifier to say whether the text is suspicious and (ii) a multiclass classifier with seven predefined categories of possibly illegal activities. The average class recall of the binary and multiclass classifiers is $$95.24\%$$

95.24
%

and $$80.33\%$$

80.33
%

, respectively. Additionally, this paper presents a dataset of 3.8 million Pastebin samples, called onlIne Notepad Services PastEbin aCtiviTies (INSPECT-3.8M), along with their labels using our classification framework. Our classifier recognised that $$7.54\%$$

7.54
%

of the collected samples are correlated with presumably criminal activities. Law enforcement agencies may benefit from the insights shared in our research when aiming to investigate or automate the monitoring of Pastebin or other Online Notepad Services. This would allow responsible authorities to block illegal content before it spreads to the public.
A novel approach for the treatment of AML, through GHRH antagonism: MIA-602
Authors: Costoya Joel , Gaumond Simonetta I. , Chale Ravinder S. , Schally Andrew V. , Jimenez Joaquin J.
Published: October 2024

Acute myeloid leukemia (AML) is the most aggressive and prevalent form of leukemia in adults. The gold-standard intervention revolves around the use of chemotherapy, and in some cases hematopoietic stem cell transplantation. Drug resistance is a frequent complication resulting from treatment, as it stands there are limited clinical measures available for refractory AML besides palliative care. The goal of this review is to renew interest in a novel targeted hormone therapy in the treatment of AML utilizing growth hormone-releasing hormone (GHRH) antagonism, given it may provide a potential solution for current barriers to achieving complete remission post-therapy. Recapitulating pre-clinical evidence, GHRH antagonists (GHRH-Ant) have significant anti-cancer activity across experimental human AML cell lines in vitro and in vivo and demonstrate significant inhibition of cancer in drug resistant analogs of leukemic cell lines as well. GHRH-Ant act in manners that are orthogonal to anthracyclines and when administered in combination synergize to produce a more potent anti-neoplastic effect. Considering the adversities associated with standard AML therapies and the developing issue of drug resistance, MIA-602 represents a novel approach worth further investigation.
Elevated Urinary Levels of Fungal and Environmental Toxins in Patients with Pancreatic Ductal Adenocarcinoma
Authors: Rodriguez Vanessa I. , Mammadova Jamila , Permuth Jennifer B. , Luthra Anjuli , Pena Luis , Friedman Mark , Dam Aamir , Cappelle Saraswathi , Malafa Mokenge P. , Hallmon Candice , Miranda Cassandra , Mok Shaffer R.S.
Published: October 2024

Background

Risk factors for pancreatic ductal adenocarcinoma (PDAC) include tobacco/alcohol abuse, genetic predisposition, insulin resistance, and pancreatic cysts. Despite these well-established risk factors and the screening of high-risk individuals, some people still develop PDAC. This study aims to explore a potential risk factor for PDAC by investigating the association between fungal toxins (FT) and environmental toxins (ET) and the disease. We predicted that individuals with PDAC would have higher levels of these toxins compared to healthy controls. The rationale behind this hypothesis is that exposure to FT and ET might contribute to the development of PDAC by elevating cancer risk.

Methods

A pilot retrospective cohort study was conducted at Moffitt Cancer Center from 2022 to 2023. This study compared FT and ET levels, demographic data, and PDAC features between subjects with PDAC and healthy controls.

Results

Forty subjects were enrolled in the study, comprising 20 with pancreatic ductal adenocarcinoma (PDAC) and 20 healthy controls. Baseline demographics were similar between the two groups. Among the PDAC subjects, the most common tumor location was the head of the pancreas (55%); 30% had locally advanced disease, 45% were borderline resectable, and 10% had metastatic disease.

Compared to the controls, subjects with PDAC had significantly higher levels of fungal toxins (FTs) including ochratoxin, gliotoxin, and citrinin (p < 0.05). Additionally, PDAC patients had significantly elevated levels of environmental toxins (ETs) such as methyl tert-butyl ether (MTBE), xylene, styrene, acrylonitrile, perchlorate, diphenyl phosphate, bromopropane, organophosphates, acrolein, tiglylglycine, and diethylphosphate (p < 0.05).

Conclusion

Our study demonstrates that subjects with PDAC, without other risk factors, have higher FT and ET levels than controls. Further studies are needed to evaluate whether ET and FT exposure can be clinically utilized as a risk factor for PDAC development.
Neutrality and Governance in a Weaponized World
Authors: Heath J. Benton
Published: October 2024

About a decade ago, the neural network of the international financial system underwent an identity crisis. Since its establishment in 1973, the Society for Worldwide Interbank Financial Telecommunication (Swift) had become the world's dominant system for transmitting information about financial transactions, handling up to 20 million messages per day across 212 jurisdictions. The Belgium-based company reached this position by providing customers with a reliable, confidential, and global system to exchange information. “[W]e have always maintained the position that we are like the internet,” Swift chief executive officer Gottfried Leibbrandt said in an October 2012 interview, “we connect everybody and we do not listen in on the conversation.” In other words, to borrow a phrase from its website, “Swift is neutral.”
Transition of buoyancy-driven flow from an axisymmetric to non-axisymmetric vortex inside an evaporating sessile droplet
Authors: Yu Jialing , Pan Zhenhai , Weibel Justin A.
Published: October 2024

The internal flow within an evaporating sessile droplet has intriguing fluid mechanics important to various microfluidics applications. In the present study, a phenomenon is observed through numerical methods wherein the buoyancy-driven flow structure inside a droplet on a non-wetting substrate transitions from an axisymmetric toroidal vortex flow to a non-axisymmetric single vortex flow with increase in the substrate temperature. As the axisymmetric nature of the droplet flow field and evaporation characteristics are broken, the internal velocity accelerates significantly. The transition, which is attributed to a flow instability inside the droplet, is more prone to occur as the droplet volume or the contact angle increases. The onset of the flow transition is analysed as the amplification of a small perturbation, thereby establishing a correlation between the flow instability and the Rayleigh number (Ra). Specifically, when Ra exceeds some critical value, the onset of the flow transition is observed, which explains the effects of substrate temperature and droplet volume on the internal flow. Next, the influence of the droplet contact angle on the critical Ra was investigated, and the underlying reasons were analysed. Finally, we discuss the heat transfer efficiency within the droplet and analyse why the internal flow tends to transition to a non-axisymmetric flow pattern from an energy minimization perspective.
Gene expression of kynurenine pathway enzymes in depression and following electroconvulsive therapy
Authors: Ryan Karen M. , Corrigan Myles , Murphy Therese M. , McLoughlin Declan M. , Harkin Andrew
Published: October 2024

Objective:

This study aimed to investigate changes in mRNA expression of the kynurenine pathway (KP) enzymes tryptophan 2, 3-dioxygenase (TDO), indoleamine 2, 3-dioxygenase 1 and 2 (IDO1, IDO2), kynurenine aminotransferase 1 and 2 (KAT1, KAT2), kynurenine monooxygenase (KMO) and kynureninase (KYNU) in medicated patients with depression (n = 74) compared to age- and sex-matched healthy controls (n = 55) and in patients with depression after electroconvulsive therapy (ECT). Associations with mood score (24-item Hamilton Depression Rating Scale, HAM-D24), plasma KP metabolites and selected glucocorticoid and inflammatory immune markers known to regulate KP enzyme expression were also explored.

Methods:

HAM-D24 was used to evaluate depression severity. Whole blood mRNA expression was assessed using quantitative real-time polymerase chain reaction.

Results:

KAT1, KYNU and IDO2 were significantly reduced in patient samples compared to control samples, though results did not survive statistical adjustment for covariates or multiple comparisons. ECT did not alter KP enzyme mRNA expression. Changes in IDO1 and KMO and change in HAM-D24 score post-ECT were negatively correlated in subgroups of patients with unipolar depression (IDO1 only), psychotic depression and ECT responders and remitters. Further exploratory correlative analyses revealed altered association patterns between KP enzyme expression, KP metabolites, NR3C1 and IL-6 in depressed patients pre- and post-ECT.

Conclusion:

Further studies are warranted to determine if KP measures have sufficient sensitivity, specificity and predictive value to be integrated into stress and immune associated biomarker panels to aid patient stratification at diagnosis and in predicting treatment response to antidepressant therapy.
A non-destructive approach in proximal sensing to assess the performance distribution of SPAD prediction models using hyperspectral analysis in apricot trees
Authors: Riefolo Carmela , D’Andrea Laura
Published: October 2024

SPAD combined with hyperspectral sensors can be an alternative approach to traditional laboratory methods for determining the physiological status of trees. The aim of this work was to assess whether the effectiveness of SPAD predictive models using hyperspectral data might be influenced by where the measurements were carried out. Leaves of apricot trees of two varieties (Farbaly and Farlis) were analysed with SPAD and spectroradiometer, and the data were organized in two different ways: (i) overall dataset (OD), collecting total measurements of trees in each variety; (ii) subset of overall datasets (SOD), collecting the measurements performed on the cardinal points of trees in each variety. Prediction models were built using as regressors: (i) spectral data transformed with Continuum Removal (CR) methodology (CR indices); (ii) vegetation indices (VI) linked to chlorophyll and nitrogen content; (iii) reflectance values associated with chlorophyll content and to wavelengths ranges where (CR) methodology was applied; (iv) reflectance values of full spectrum. The best performances belonged to models using wider ranges of spectrum both in ODs and in SODs. The north cardinal point showed prediction models with the best performances in both varieties. No VI and CR indices showed reliable models. All the reliable prediction models were associated with compounds involved in physiological state and metabolism of leaves in apricot tree.
Napoleon, the Last Émigrés, and the Limits of Amnesty
Authors: Carapella Timothy
Published: October 2024

Even as emperor, Napoleon was concerned with the émigrés. Although his general amnesty for the émigrés, which was promulgated on 26 April 1802, permitted most of the émigrés still inscribed on the ‘general list’ to return to France, it also excluded those belonging to six compromised categories. The number of these exceptions was not to exceed 1,000, the decree stipulating that the first 500 should be named within four months. As it turns out, it actually took the Ministry of Police more than two years to prepare a draft list of exceptions, which ran to more than 800 names. But it was not until 1807 that the first official list of émigrés (la première liste de maintenue) was finally decreed. Surprisingly, that list contained only 171 names. A second list released in 1810 added only 29 more. Examining these much-reduced lists, which have been almost entirely ignored, throws useful light on Napoleon’s continuing worries about the émigrés after 1804. For even then, he saw the Bourbons and the last émigrés as his personal enemies, threats to the security of the Empire, and possibly even reminders of what he saw as his fragile political legitimacy.
An ambivalent approach to disability in older age: evidence from reporting by states parties under the UN Convention on the Rights of Persons with Disabilities
Authors: Leahy Ann
Published: October 2024

Issues of ‘disability’ and ‘ageing’ are usually approached separately in theorising, activism and policy making. Yet people with disabilities age and many people will experience disability if they live long enough. Human rights approaches to disability enshrined in the UN Convention on the Rights of Persons with Disabilities (CRPD) are not often applied to older people experiencing disability. This article presents findings of a systematic qualitative analysis of reports made by 28 European states to the UN Committee on the Rights of Persons with Disabilities, the independent body that monitors CRPD implementation, focusing particularly on Article 19 CRPD (‘Living independently and being included in the community’). While states’ reports refer to older people or ageing in different contexts, their approach can be characterised as ambivalent. Reports tend to constitute older people experiencing disability as ‘older’ rather than ‘disabled’; they do not demonstrate a thorough engagement with disability experienced in older age, and display a limited focus on people ageing with lifelong disability. Several reports detail exclusions of ‘older people’ from disability supports to live in the community and some exclude impairments associated with ageing from definitions of what ‘disability’ is. The reports provide almost no evidence of consultation with organisations working on ageing. The article concludes that while the CRPD’s potential to contribute to realising rights for older people with disabilities is under-recognised among scholars and non-governmental organisations, the fact that states refer to older people in their reporting under the CRPD provides a starting point for more engagement.
Cost and resource comparison analysis for THA in Switzerland and Austria
Authors: Blümel Stefan , Hanauer Matthieu , Heimann Alexander , Tannast Moritz , Schwab Joseph M.
Published: October 2024

Objectives

Total hip arthroplasty (THA) is an orthopedic intervention that generates substantial costs to national healthcare systems due to the number of interventions and the cost per intervention. We performed a cost comparison analysis in Austria and Switzerland.

Methods

Data from the national joint arthroplasty register in Switzerland and internal information from the national healthcare services in Austria and Switzerland were compared for patient demographics, interventional characteristics, and costs adjusted for inflation and purchasing power from 2015 to 2021.

Results

The average age for primary THA in Austria was from 67.4 to 67.8 years with 55.9–57.2 percent female patients and from 68.5 to 69.3 years with 52.4–53.8 percent female patients in Switzerland. The annual incidence rate for primary THA rose from 210.28/100k to 216.6/100k in Austria and from 212/100k to 250/100k in Switzerland. After correction for inflation, costs were −1.91 percent lower in Austria in 2021 than in 2015 and −2.57 percent lower in Switzerland. After correction for purchasing power, costs were higher in Austria. The average hospital stay after THA in Austria was reduced by 20 percent (11.7 days/2015 vs. 9.4 days/2021) and 25 percent in Switzerland (8.4 days/2015 vs. 6.4 days/2021). Revision rate was 2.5–3.2 percent in Austria and 2.8–3.2 percent in Switzerland.

Conclusions

The patient population was comparable while patients undergoing primary THA in Austria stay longer in hospital and have relatively higher costs when adjusted for currency, purchasing power, and inflation. The use of standardized registers would be helpful to compare outcomes and costs.
Clausal Postpositioning in German Regional Language
Authors: Dubenion-Smith Shannon
Published: October 2024

This article presents the results of a corpus study of clausal postpositioning, that is, the occurrence of a sentential constituent in the postfield of the matrix clause to which it is syntactically linked, in German regional language. Analysis of 11,027 clauses from 60 spoken regiolect and dialect texts reveals that clausal postpositionings occur most frequently as non-relative finite clauses, followed by relative clauses, and lastly, infinitival constructions. Notably, while non-relative finite clauses comprise a smaller proportion of postpositionings in regiolect compared to dialect, relative clauses and infinitival constructions show the opposite trend. Adjunct clauses occur most frequently, followed by complement clauses, in both regiolect and dialect. Furthermore, in both varieties, postpositioning is more prevalent in verb-first and verb-second clauses than in verb-final clauses. This finding is attributed to restrictions on syntactic subordination. Finally, non-relative finite clause and relative clause types that may be embedded in both the postfield and inner field are center-embedded at mean relative frequencies of 13.42% and 28.17%, respectively. These findings shed light on contradictory claims in the literature regarding the possibility and frequency of clausal embedding in the inner field.