bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modulating the tumor microenvironment in a mouse model of colon cancer using a combination of HIF-1α inhibitors and Toll-Like Receptor 7 agonists
Authors: Rostamizadeh Leila , Ramezani Mina , Monirinasab Hannaneh , Rostamizadeh Kobra , Sabzichi Mehdi , Bahavarnia Seied Rafi , Osouli-Bostanabad Karim , Ramezani Fatemeh , Molavi Ommoleila 
Published: November 2024

Abstract
The immunosuppressive tumor microenvironment (TME) plays a pivotal role in the response to various anticancer therapies, such as immune and chemotherapeutic agents. In this study, the synergistic effects of gene-targeting HIF-1α siRNA combined with Toll-Like Receptor 7 agonist on TME remodeling were investigated in a mouse model of colorectal cancer (CRC). A HIF-1α-specific siRNA duplex was formulated based on the ionic gelation of tripolyphosphate (TPP) with cationic chitosan (CH) as a nanoplex and evaluated in terms of size, charge, polydispersity index and gel retardation assay. MTT assay was conducted to assess the cytotoxicity of the specific siRNA duplex against CT26 cells. Hypoxic condition was generated to evaluate the gene and protein expression levels of HIF-1α, respectively. CT26 mouse model was established to assess the synergistic effect of silencing HIF-1α combined with oxaliplatin (OXA) and imiquimod (IMQ) on tumor growth. The mean diameter of the CH/siRNA nanoparticles was 243 ± 6 nm, as confirmed with Micrograph scanning electron microscope. There were no significant differences observed between the CT26 cells treated with nanoparticles alone and the untreated cells, indicating that these nanoparticles are safe and physiologically biocompatible (p ≥ 0.05). Triple combination therapy involving HIF-1α siRNA, OXA, and IMQ significantly retarded tumor growth and led to elevated levels of cytokines linked to cellular immunity (INF-γ and IL-12) compared with those in the other groups (P < 0.05). The positive correlation coefficient (r = 0.68) between tumor size and HIF-1α expression levels was statistically significant (P = 0.003). Compared with those in the control group, the expression levels of the anti-inflammatory cytokines IL-10 and IL-4 significantly decreased (P < 0.05). In conclusion, our findings suggest that inhibiting HIF-1α could serve as a rational strategy to enhance the antitumor response in the TME.
Reliable diagnosis of nigrostriatal degeneration by dopamine transporter SPECT despite drug interaction with venlafaxine or bupropion
Authors: Apostolova Ivayla , Hellwig Sabine , Karimzadeh Amir , Klutmann Susanne , Meyer Philipp T. , Buchert Ralph 
Published: November 2024

Abstract

Purpose
This study examined the impact of venlafaxine and bupropion on the detection of nigrostriatal degeneration by dopamine transporter (DAT)-SPECT.

Methods
43 patients (70.7 ± 8.6y, 44% female) with [123I]FP-CIT-SPECT under venlafaxine (n = 26, 37.5-225 mg/d), bupropion (n = 16, 150 or 300 mg/d) or both (n = 1) were included retrospectively. The striatal specific [123I]FP-CIT binding ratio (SBR), its left–right asymmetry and the putamen-to-caudate ratio were transformed to z-scores and submitted to a cluster analysis for data-driven categorization.

Results
Two clusters were identified. The first cluster (37% cases) showed a Parkinson’s disease (PD)-like pattern: median striatal SBR/asymmetry/putamen-to-caudate z-score -4.5/4.9/-3.8. The second cluster (63%) showed symmetric reduction with normal intra-striatal gradient: median striatal SBR/asymmetry/putamen-to-caudate z-score -2.7/0.4/0.2. Patients with follow-up clinical reference diagnoses of neurodegenerative (n = 8) and non-neurodegenerative (n = 16) parkinsonism fell exclusively into the former or the latter cluster, respectively (p < 0.001).

Conclusion
Venlafaxine and bupropion cause uniform reduction of the striatal [123I]FP-CIT SBR that can be distinguished from PD-like reductions.
Albumin-muscle density score predicts overall survival in patients with hepatocellular cancer undergoing treatment with transarterial chemoembolization
Authors: Surov Alexey , Wienke Andreas , Borggrefe Jan , Auer Timo Alexander , Gebauer Bernhard , Mähringer-Kunz Aline , Nensa Felix , Haubold Johannes , Schaarschmidt Benedikt Michael , Hosch René , Kleesiek Jens , Diallo Thierno D. , Roehlen Natascha , Bettinger Dominik , Eisenblätter Michel , Steinle Verena , Mayer Philipp , Zopfs David , Pinto dos Santos Daniel , Müller Lukas , Kloeckner Roman 
Published: November 2024

Abstract
Purpose
The purpose of the present study was to analyze associations between different skeletal muscle quality parameters and survival in patients with hepatocellular carcinoma (HCC) undergoing treatment with transarterial chemoembolization (TACE).

Methods
We retrospectively enrolled 784 treatment-naïve patients with HCC undergoing TACE at six tertiary care centers between 2010 and 2020. Intramuscular adipose tissue (IMAT) and skeletal muscle density (SMD) were estimated. Myosteatosis was defined as SMD < 28.0 HU for men and < 23.8 HU for women. Furthermore, albumin-SMD score (ADS) was calculated as follows: serum albumin (g/dL) × SMD (HU). To assess the impact of muscle quality on survival, Cox regression model was used. Kaplan-Meier curves were used for survival analysis. Parameters of skeletal muscle quality were compared in univariate and multivariate regression analyses, adjusted for established risk factors.

Results
In the overall sample, survivors had higher SMD and ADS in comparison to non-survivors. Patients with low ADS had a lower OS than patients with high ADS (8.4 vs. 14.3 months, p < 0.001). In alcohol-induced HCC, none of the analyzed parameters of muscle quality influenced survival. In viral induced HCC, patients with low ADS had lower OS than patients with high ADS (8.8 vs. 15.7 months, p < 0.001). In patients with non-alcoholic steatohepatitis (NASH), none of the analyzed parameters of muscle quality influenced survival.

Conclusions
Low ADS is an independent predictor of worse OS in patients with viral-induced HCC undergoing treatment with TACE. In alcohol-induced and NASH-induced HCCs, parameters of muscle quality do not influence OS.
Evaluation of predictive performance of fetal urinary inflammatory markers of postnatal kidney function in fetuses with posterior urethral valves
Authors: Geraud Nicolas , Casemayou Audrey , Alves Melinda , Breuil Benjamin , Tkaczyk Marcin , Stańczyk Małgorzata , Szaflik Krzysztof , Talar Tomasz , Decramer Stéphane , Klein Julie , Schanstra Joost P. , Meyer Bénédicte Buffin 
Published: November 2024

Abstract
Background
There are proposed roles for inflammation in the development of congenital obstructive uropathy in the setting of posterior urethral valves (PUV). However, the value of inflammatory proteins as predictive markers of postnatal kidney function, key in the management of fetuses with PUV, has not been explored. We screened fetal urine of fetuses with PUV with a panel of inflammatory proteins to determine their predictive value of postnatal kidney function.

Methods
Twenty-five different chemokines and cytokines were measured using a multiplex immunoassay in fetal urine of 79 PUV patients from retrospective cohorts, separated in discovery (n = 52) and validation (n = 27). The candidate markers were also quantified in amniotic fluid samples obtained from 16 PUV and 25 other congenital anomalies of the kidney and the urinary tract pregnancies. The performance of validated candidate inflammatory proteins was compared to the previously published 12PUV fetal urine peptide signature.

Results
Fetal urine chemokines CCL2 (MCP-1), CXCL9 (MIG), and CCL4 (MIP-1β) were identified as predictive of postnatal kidney failure in fetuses with PUV from the discovery cohort. Their predictive potential was confirmed in the validation cohort (AUCs of 0.87, 0.81, and 0.86, respectively). The performance of these individual chemokines was lower than the previously published 12PUV fetal urine peptide signature. However, the combination of the three chemokines performed similarly to 12PUV. In contrast, these three chemokines were not predictive of outcome in amniotic fluid.

Conclusions
We identified chemokines in fetal urine of PUV pregnancies that, after external validation, could serve as predictive biomarkers of postnatal outcome and contribute to improve prenatal PUV management.

Graphical Abstract
Recent novelties in research and management of cerebrospinal cavernous malformations
Authors: Rauschenbach Laurèl , Dammann Philipp , Sure Ulrich 
Published: November 2024

Abstract
In recent years, knowledge about cerebrospinal cavernomas has grown considerably, leading to the development of initial guidelines and treatment recommendations. However, due to the rarity and heterogeneity of the disease, the level of evidence remains limited, leaving many questions unanswered and subject to ongoing debate. Therefore, an up-to-date review of this field's latest developments and controversies is reasonable.
Traumatic posterior fossa extradural hematoma in children: a meta-analysis and institutional experience of its clinical course, treatment and outcomes
Authors: Lee Keng Siang , Ong Shi Hui , Gillespie Conor S , Ng Lee Ping , Seow Wan Tew , Low Sharon YY 
Published: November 2024

Abstract
Posterior fossa extradural hematoma (PFEDH) is rare but has a greater incidence amongst children. It is also associated with a rapid deterioration. The aim of this study was to present the management of PFEDH through our institutional experience and a meta-analysis. A retrospective single institution review of all children from 2004 to 2024 who underwent craniotomy for PFEDH was undertaken. The collected variables included: demographics, type of trauma, clinical findings, computed tomography findings, and clinical course. A systematic review using Ovid Medline, Ovid Embase, and Cochrane Central Register of Controlled Trials (CENTRAL), and meta-analysis were performed. Nineteen children with PFEDH who underwent surgery were identified. All 19 (100%) patients benefited from good Glasgow Outcome Scale (GOS) score 4–5, and there were no incidences of in-hospital mortality. From the systematic review, 391 patients, across twenty-four studies and our series, were included. A total of 308 were treated with surgery, whereas 83 patients were treated conservatively. A comparative meta-analysis was not performed as the two groups were deemed too heterogeneous in clinical characteristics. Instead, single-arm meta-analyses were performed. The pooled incidence of patients initially under conservative management requiring surgery was 9.90% (95%CI 1.61;22.21%, I2 = 35.2). The incidence of good functional outcomes in patients managed surgically and conservatively were 93.68% (95%CI: 88.69;97.57%, I2 = 0.0%), and 99.99% (95%CI: 96.53;100%, I2 = 0.0%), respectively. Overall pooled of mortality in patients managed surgically and conservatively were 0.57% (95%CI: 0.00;2.87%, I2 = 0.0%) and 0.00% (95%CI: 0.00;1.18%, I2 = 0.0%). Overall, our study reiterates that pediatric PFEDH is uncommon, and patients often present atypically. Based on our institutional experience and extrapolating data from our meta-analysis of the wider literature, neurosurgical intervention is a reliable therapeutic option with good clinical outcomes.
Blood volume deficit in postural orthostatic tachycardia syndrome assessed by semiautomated carbon monoxide rebreathing
Authors: Kulapatana Surat , Urechie Vasile , Rigo Stefano , Mohr Abigail , Vance Yuliya A. , Okamoto Luis E. , Gamboa Alfredo , Shibao Cyndya , Biaggioni Italo , Furlan Raffaello , Diedrich André 
Published: November 2024

Abstract
Purpose
The semiautomated carbon monoxide (CO) rebreathing method has been introduced as a noninvasive and radiation-free blood volume estimation method. We tested whether the semiautomated CO rebreathing method can detect the blood volume deficit in postural orthostatic tachycardia syndrome (POTS). In addition, we explored the relationship between blood volume estimated from CO rebreathing and body impedance.

Patients and methods
We recruited 53 subjects (21 female patients with POTS, 19 healthy female participants, and 13 healthy male participants) to record blood volumes and hemodynamic data. Blood volumes were measured by CO rebreathing and segmental body impedance. Linear regression models to predict normal values of red blood cell volume (RBCV), plasma volume (PV), and total blood volume (BV) were developed. Percentage deviations from the predicted normal volumes were calculated.

Results
Patients with POTS had lower RBCV (25.18 ± 3.95 versus 28.57 ± 3.68 mL/kg, p = 0.008, patients with POTS versus healthy female participants), BV (64.53 ± 10.02 versus 76.78 ± 10.00 mL/kg, p < 0.001), and BV deviation (−13.92 ± 10.38% versus −0.02 ± 10.18%, p < 0.001). Patients with POTS had higher supine heart rate (HR) (84 ± 14 versus 69 ± 11 bpm, p < 0.001) and upright HR (123 ± 23 versus 89 ± 22 bpm, p < 0.001). We found a correlation between BV deviation and upright HR in patients with POTS (r = −0.608, p = 0.003), but not in healthy participants. Volumes from the CO rebreathing and body impedance were well correlated (r = 0.629, p < 0.001).

Conclusions
The CO rebreathing method can detect BV deficit, as well as the RBCV deficit in patients with POTS. The negative correlation between BV deviation and upright HR indicates that hypovolemia is one of the pathophysiological causes of POTS. Correlations between body impedance and CO rebreathing volume suggest its usefulness for measurements of volume changes.
The research landscape of industry 5.0: a scientific mapping based on bibliometric and topic modeling techniques
Authors: Rejeb Abderahman , Rejeb Karim , Zrelli Imen , Kayikci Yasanur , Hassoun Abdo 
Published: November 2024

AbstractIndustry 5.0 (I5.0) marks a transformative shift toward integrating advanced technologies with human-centric design to foster innovation, resilient manufacturing, and sustainability. This study aims to examine the evolution and collaborative dynamics of I5.0 research through a bibliometric analysis of 942 journal articles from the Scopus database. Our findings reveal a significant increase in I5.0 research, particularly post-2020, yet highlight fragmented collaboration networks and a noticeable gap between institutions in developed and developing countries. Key thematic areas identified include human-robot collaboration, data management and security, AI-driven innovation, and sustainable practices. These insights suggest that a more integrated approach is essential for advancing I5.0, calling for strengthened global collaborations and a balanced emphasis on both technological and human-centric elements to fully realize its potential in driving resilient and sustainable industrial practices. This study provides the first comprehensive bibliometric analysis of I5.0, offering valuable insights for both researchers and practitioners.
Copper-enriched hydroxyapatite coatings obtained by high-velocity suspension flame spraying. Effect of various gas parameters on biocompatibility
Authors: Le Long-Quan R. V. , Lanzino M. Carolina , Blum Matthias , Höppel Anika , Al-Ahmad Ali , Killinger Andreas , Gadow Rainer , Rheinheimer Wolfgang , Seidenstuecker Michael 
Published: November 2024

AbstractHydroxyapatite (HAp)-coated bone implants are frequently used for orthopaedic or dental implants since they offer high biocompatibility and osteoconductivity. Yet, problems such as infections, e.g. periprosthetic joint infections, occur when implanting foreign material into the body. In this study, HAp coatings were produced via high-velocity suspension flame spraying (HVSFS). This method allows for the production of thin coatings. We investigated the effects of different gas parameters on the coating properties and on the biocompatibility, which was tested on the human osteosarcoma cell line MG63. Furthermore, Copper (Cu) was added to achieve antibacterial properties which were evaluated against standard microorganisms using the airborne assay. Three gas parameter groups (low, medium, and high) with different Cu additions (0 wt.%, 1 wt.% and 1.5 wt.%) were evaluated. Our findings show that porosity as well as hardness can be controlled through gas parameters. Furthermore, we showed that it is possible to add Cu through external injection. The Cu content in the coating as well as the release varies with different gas parameters. Both antibacterial efficacy as well as biocompatibility are affected by the Cu content. We could significantly reduce the amount of colony-forming units (CFU) in all coatings for E. coli, CFU for S. aureus was reduced by adding 1.5 wt.% of Cu to the coating. The biocompatibility testing showed a cytotoxicity threshold at a Cu-release of 14.3 mg/L in 120 hours. Based on our findings, we suggest medium gas parameters for HVSFS and the addition of 1 wt.% Cu to the coating. With these parameters, a reasonable antibacterial effect can be achieved while maintaining sufficient biocompatibility.
Graphical Abstract
Induction of Neural Differentiation and Protection by a Novel Slow-Release Nanoparticle Estrogen Construct in a Rat Model of Spinal Cord Injury
Authors: Haque Azizul , Zaman Vandana , Drasites Kelsey P. , Matzelle Denise , Sawant Sushant , Vertegel Alexey , Varma Abhay , Banik Naren L. 
Published: November 2024

Abstract
Spinal cord injury (SCI) is a complex debilitating condition leading to permanent life-long neurological deficits. Estrogen (E2) treatment is known to be neuroprotectant in SCI. This hormone is highly pleiotropic and has been shown to decrease apoptosis, modulate calcium signaling, regulate growth factor expression, act as an anti-inflammatory, and drive angiogenesis. These beneficial effects were found in our earlier study at the low dose of 10 µg/kg E2 in rats. However, the dose remains non-physiologic, which poses a safety hurdle for clinical use. Thus, we recently devised/constructed a fast release nanoparticle (NP) estrogen embedded (FNP-E2) construct and tested a focal delivery system in a contused SCI rat model which showed protection in the short run. In the current study, we have developed a novel slow-release NP estrogen (SNP-E2) delivery system that shows sustained release of E2 in the injured spinal cord and no systemic exposure in the host. The study of E2 release and kinetics of this SNP-E2 construct in vitro and in vivo supported this claim. Delivery of E2 to the injured spinal cord via this approach reduced inflammation and gliosis, and induced microglial differentiation of M1 to M2 in rats after SCI. Analysis of spinal cord samples showed improved myelination and survival signals (AKT) as demonstrated by western blot analysis. SNP-E2 treatment also induced astrocytic differentiation into neuron-like (MAP2/NeuN) cells, supported the survival of oligodendrocyte precursor cells (OPC), and improved bladder and locomotor function in rats following SCI. These data suggest that this novel delivery strategy of SNP-E2 to the injured spinal cord may provide a safe and effective therapeutic approach to treat individuals suffering from SCI.
Reliable individual differences in researcher performance capacity estimates: evaluating productivity as explanatory variable
Authors: Forthmann Boris , Beisemann Marie , Doebler Philipp , Mutz Rüdiger 
Published: November 2024

Abstract
Are latent variables of researcher performance capacity merely elaborate proxies of productivity? To investigate this research question, we propose extensions of recently used item-response theory models for the estimation of researcher performance capacity. We argue that productivity should be considered as a potential explanatory variable of reliable individual differences between researchers. Thus, we extend the Conway-Maxwell Poisson counts model and a negative binomial counts model by incorporating productivity as a person-covariate. We estimated six different models: a model without productivity as item and person-covariate, a model with raw productivity as person-covariate, a model with log-productivity as person covariate, a model that treats log-productivity as a known offset, a model with item-specific influences of productivity, and a model with item-specific influences of productivity as well as academic age as person-covariate. We found that the model with item-specific influences of productivity fitted two samples of social science researchers best. In the first dataset, reliable individual differences decreased substantially from excellent reliability when productivity is not modeled at all to inacceptable levels of reliability when productivity is controlled as a person-covariate, while in the second dataset reliability decreased only negligibly. This all emphasizes the critical role of productivity in researcher performance capacity estimation.
Learning from interactive video: the influence of self-explanations, navigation, and cognitive load
Authors: Beege Maik , Ploetzner Rolf 
Published: November 2024

Abstract
Recent research has shown that enhancing instructional videos with questions, such as self-explanation prompts, and thus shifting the process from receptive to constructive learning, is beneficial to learning. However, the inclusion of questions is often confounded with the implementation of learner pacing through navigation features. Furthermore, previous studies have often not controlled for learning time. To address these shortcomings, an experiment (N = 128) was conducted. Participants watched an instructional video about cloud formation and lightning, with learning time controlled. In a 2 × 2 between-subjects design, navigation features (learner pacing vs. system pacing) and self-explanation prompts (prompts vs. no prompts) were manipulated. The results showed no effects of navigation features and self-explanation prompts on learning performance. While navigation features did not affect cognitive load, self-explanation prompts increased both intrinsic and extraneous cognitive load. Overall, the quality of responses to prompts was low but positively related to comprehension. The results are discussed in terms of the Interactive-Constructive-Active-Passive framework and Cognitive Load Theory. They highlight the importance of boundary conditions when investigating the effects of interactive features in instructional videos.
Dirty habits: potential for spread of antibiotic-resistance by black-headed gulls from waste-water treatment plants
Authors: Martín-Vélez Víctor , Navarro Joan , Vazquez Manuel , Navarro-Ramos María J. , Bonnedahl Jonas , van Toor Mariëlle L. , Bustamante Javier , Green Andy J. 
Published: November 2024

AbstractAnthropogenic environments such as wastewater treatment plants (WWTPs) and landfills are sources of antimicrobial resistance (AMR). Black-headed gulls (Chroicocephalus ridibundus) frequently use WWTPs and may be vectors for AMR. We used GPS tracking data for 39 gulls for up to 8 months, combined with a shedding curve, to study sources and dispersal distances of AMR in Iberia. The gulls used 21 different WWTPs (684 visits) and three landfills (21 visits). Areas of high risk of AMR dissemination were an average of 25 km from the infection source, with a maximum of 500 km. Solar saltworks and natural waterbodies were particularly exposed to AMR dissemination, followed by agriculture, sports facilities, and tourist beaches. There was important variability between individual gulls in their habitat specialization, and which WWTPs they visited. Studying the spatial movements of gulls after visiting WWTPs and landfills helps pinpoint sensitive locations where pathogen transmission is most likely.