bluuebunny/crossref_metadata_2025_split huggingface dataset:
Matching proposed clinical and MRI criteria of aggressive multiple sclerosis to serum and cerebrospinal fluid markers of neuroaxonal and glial injury
Authors: Schaller-Paule Martin A. , Maiworm Michelle , Schäfer Jan Hendrik , Friedauer Lucie , Hattingen Elke , Wenger Katharina Johanna , Weber Frank , Jakob Jasmin , Steffen Falk , Bittner Stefan , Yalachkov Yavor , Foerch Christian 
Published: March 2024

Abstract
Background
Definitions of aggressive MS employ clinical and MR imaging criteria to identify highly active, rapidly progressing disease courses. However, the degree of overlap between clinical and radiological parameters and biochemical markers of CNS injury is not fully understood. Aim of this cross-sectional study was to match clinical and MR imaging hallmarks of aggressive MS to serum/CSF markers of neuroaxonal and astroglial injury (neurofilament light chain (sNfL, cNfL), and glial fibrillary acidic protein (sGFAP, cGFAP)).

Methods
We recruited 77 patients with relapsing–remitting MS (RRMS) and 22 patients with clinically isolated syndrome. NfL and GFAP levels in serum and CSF were assessed using a single-molecule-array HD-1-analyzer. A general linear model with each biomarker as a dependent variable was computed. Clinical and imaging criteria of aggressive MS, as recently proposed by the ECTRIMS Consensus Group, were modeled as independent variables. Other demographic, clinical or laboratory parameters, were modeled as covariates. Analyses were repeated in a homogenous subgroup, consisting only of newly diagnosed, treatment-naïve RRMS patients presenting with an acute relapse.

Results
After adjusting for covariates and multiplicity of testing, sNfL and cNfL concentrations were strongly associated with the presence of ≥2 gadolinium-enhancing lesions (psNfL = 0.00008; pcNfL = 0.004) as well as the presence of infratentorial lesions on MRI (psNfL = 0.0003; pcNfL < 0.004). No other clinical and imaging criteria of aggressive MS correlated significantly with NfL or GFAP in serum and CSF. In the more homogeneous subgroup, sNfL still was associated with the presence of ≥2 gadolinium-enhancing lesions (psNfL = 0.001), presence of more than 20 T2-lesions (psNfL = 0.049) as well as the presence of infratentorial lesions on MRI (psNfL = 0.034), while cNfL was associated with the presence of ≥2 gadolinium-enhancing lesions (psNfL = 0.011) and presence of more than 20 T2-lesions (psNfL = 0.029).

Conclusions
Among proposed risk factors for an aggressive disease course, MRI findings but not clinical characteristics correlated with sNfL and cNfL as a marker of neuroaxonal injury and should be given appropriate weight considering MS prognosis and therapy. No significant correlation was detected for GFAP alone.
Liraglutide versus pramlintide in protecting against cognitive function impairment through affecting PI3K/AKT/GSK-3β/TTBK1 pathway and decreasing Tau hyperphosphorylation in high-fat diet- streptozocin rat model
Authors: Moghazy Hoda M. , Abdelhaliem Nesreen G , Mohammed Sherine Ahmed , Hassan Asmaa , Abdelrahman Amany 
Published: March 2024

AbstractThe American Diabetes Association guidelines (2021) confirmed the importance of raising public awareness of diabetes-induced cognitive impairment, highlighting the links between poor glycemic control and cognitive impairment. The characteristic brain lesions of cognitive dysfunction are neurofibrillary tangles (NFT) and senile plaques formed of amyloid-β deposition, glycogen synthase kinase 3 beta (GSK3β), and highly homologous kinase tau tubulin kinase 1 (TTBK1) can phosphorylate Tau proteins at different sites, overexpression of these enzymes produces extensive phosphorylation of Tau proteins making them insoluble and enhance NFT formation, which impairs cognitive functions. The current study aimed to investigate the potential contribution of liraglutide and pramlintide in the prevention of diabetes-induced cognitive dysfunction and their effect on the PI3K/AKT/GSK-3β/TTBK1 pathway in type 2 diabetic (T2D) rat model. T2D was induced by administration of a high-fat diet for 10 weeks, then injection of a single dose of streptozotocin (STZ); treatment was started with either pramlintide (200 μg/kg/day sc) or liraglutide (0.6 mg/kg/day sc) for 6 weeks in addition to the HFD. At the end of the study, cognitive functions were assessed by novel object recognition and T-maze tests. Then, rats were sacrificed for biochemical and histological assessment of the hippocampal tissue. Both pramlintide and liraglutide treatment revealed equally adequate control of diabetes, prevented the decline in memory function, and increased PI3K/AKT expression while decreasing GSK-3β/TTBK1 expression; however, liraglutide significantly decreased the number of Tau positive cells better than pramlintide did. This study confirmed that pramlintide and liraglutide are promising antidiabetic medications that could prevent associated cognitive disorders in different mechanisms.
The pain target NaV1.7 is expressed late during human iPS cell differentiation into sensory neurons as determined in high-resolution imaging
Authors: Liu Yi , Balaji Rachna , de Toledo Marcelo A. Szymanski , Ernst Sabrina , Hautvast Petra , Kesdoğan Aylin B. , Körner Jannis , Zenke Martin , Neureiter Anika , Lampert Angelika 
Published: March 2024

AbstractHuman-induced pluripotent stem cells (iPS cells) are efficiently differentiated into sensory neurons. These cells express the voltage-gated sodium channel NaV1.7, which is a validated pain target. NaV1.7 deficiency leads to pain insensitivity, whereas NaV1.7 gain-of-function mutants are associated with chronic pain. During differentiation, the sensory neurons start spontaneous action potential firing around day 22, with increasing firing rate until day 40. Here, we used CRISPR/Cas9 genome editing to generate a HA-tag NaV1.7 to follow its expression during differentiation. We used two protocols to generate sensory neurons: the classical small molecule approach and a directed differentiation methodology and assessed surface NaV1.7 expression by Airyscan high-resolution microscopy. Our results show that maturation of at least 49 days is necessary to observe robust NaV1.7 surface expression in both protocols. Electric activity of the sensory neurons precedes NaV1.7 surface expression. A clinically effective NaV1.7 blocker is still missing, and we expect this iPS cell model system to be useful for drug discovery and disease modeling.
Blood pressure in preterm infants with bronchopulmonary dysplasia in the first three months of life
Authors: Kiss Judit Klara , Gajda Anna , Mari Judit , Bereczki Csaba 
Published: March 2024

Abstract
Background
Neonatal hypertension is common in preterm infants with bronchopulmonary dysplasia (BPD). Our study aimed to examine blood pressure variation in the first three months of life in preterm BPD patients.

Methods
We conducted a retrospective, single-centre study at the Neonatal Intensive Care Unit of the University of Szeged, Hungary. We collected blood pressure data from 26 preterm infants (born at < 30 weeks gestation) with moderate or severe BPD over three years (2019–2021). We calculated the BPD group's daily average blood pressure values and used previously defined normal blood pressure values from a preterm patient group born at < 30 weeks gestation as a reference. We used 19,481 systolic, diastolic and mean blood pressure measurement data separately to calculate daily average blood pressures.

Results
We found a statistically significant correlation between the blood pressure values of the BPD patient group and the reference data. The difference between the blood pressure curve of the group with BPD and that of the reference group was also statistically significant. We also analysed individual patients' daily average blood pressure values and found that 11 patients (42%) had hypertensive blood pressure values for three or more days within the first 90 days of life. Within this group, our statistical analysis showed a 25% chance of acute kidney injury.

Conclusion
The blood pressure of the BPD group not only correlated with but also significantly differed from the reference data. Hypertension lasting three or more days occurred more frequently in patients with acute kidney injury accompanied by BPD.

Graphical abstract
Efficient economic operation based on load dispatch of power systems using a leader white shark optimization algorithm
Authors: Hassan Mohamed H. , Kamel Salah , Selim Ali , Shaheen Abdullah , Yu Juan , El-Sehiemy Ragab 
Published: March 2024

AbstractThis article proposes the use of a leader white shark optimizer (LWSO) with the aim of improving the exploitation of the conventional white shark optimizer (WSO) and solving the economic operation-based load dispatch (ELD) problem. The ELD problem is a crucial aspect of power system operation, involving the allocation of power generation resources to meet the demand while minimizing operational costs. The proposed approach aims to enhance the performance and efficiency of the WSO by introducing a leadership mechanism within the optimization process, which aids in more effectively navigating the complex ELD solution space. The LWSO achieves increased exploitation by utilizing a leader-based mutation selection throughout each generation of white sharks. The efficacy of the proposed algorithm is tested on 13 engineer benchmarks non-convex optimization problems from CEC 2020 and compared with recent metaheuristic algorithms such as dung beetle optimizer (DBO), conventional WSO, fox optimizer (FOX), and moth-flame optimization (MFO) algorithms. The LWSO is also used to address the ELD problem in different case studies (6 units, 10 units, 11 units, and 40 units), with 20 separate runs using the proposed LWSO and other competitive algorithms being statistically assessed to demonstrate its effectiveness. The results show that the LWSO outperforms other metaheuristic algorithms, achieving the best solution for the benchmarks and the minimum fuel cost for the ELD problem. Additionally, statistical tests are conducted to validate the competitiveness of the LWSO algorithm.
Pioneering electrochemical detection unveils erdafitinib: a breakthrough in anticancer agent determination
Authors: Yildir Merve Hatun , Genc Asena Ayse , Erk Nevin , Bouali Wiem , Bugday Nesrin , Yasar Sedat , Duygulu Ozgur 
Published: March 2024

Abstract The successful fabrication is reported of highly crystalline Co nanoparticles interconnected with zeolitic imidazolate framework (ZIF-12) -based amorphous porous carbon using the molten-salt-assisted approach utilizing NaCl. Single crystal diffractometers (XRD), and X-ray photoelectron spectroscopy (XPS) analyses confirm the codoped amorphous carbon structure. Crystallite size was calculated by Scherrer (34 nm) and Williamson-Hall models (42 nm). The magnetic properties of NPCS (N-doped porous carbon sheet) were studied using a vibrating sample magnetometer (VSM). The NPCS has a magnetic saturation (Ms) value of 1.85 emu/g. Scanning electron microscopy (SEM) and transmission electron microscopy (TEM) analyses show that Co/Co3O4 nanoparticles are homogeneously distributed in the carbon matrix. While a low melting point eutectic salt acts as an ionic liquid solvent, ZIF-12, at high temperature, leading cobalt nanoparticles with a trace amount of Co3O4 interconnected by conductive amorphous carbon. In addition, the surface area (89.04 m2/g) and pore architectures of amorphous carbon embedded with Co nanoparticles are created using the molten salt approach. Thanks to this inexpensive and effective method, the optimal composite porous carbon structures were obtained with the strategy using NaCl salt and showed distinct electrochemical performance on electrochemical methodology revealing the analytical profile of Erdatifinib (ERD) as a sensor modifier. The linear response spanned from 0.01 to 7.38 μM, featuring a limit of detection (LOD) of 3.36 nM and a limit of quantification (LOQ) of 11.2 nM. The developed sensor was examined in terms of selectivity, repeatability, and reproducibility. The fabricated electrode was utilized for the quantification of Erdafitinib in urine samples and pharmaceutical dosage forms. This research provides a fresh outlook on the advancements in electrochemical sensor technology concerning the development and detection of anticancer drugs within the realms of medicine and pharmacology.
Graphical Abstract
Improved coverage factors for expanded measurement uncertainty calculated from two estimated variance components
Authors: Rostron Peter D. , Fearn Tom , Ramsey Michael H. 
Published: March 2024

AbstractMeasurement uncertainty (MU) arising at different stages of a measurement process can be estimated using analysis of variance (ANOVA) on replicated measurements. It is common practice to derive an expanded MU by multiplying the resulting standard deviation by a coverage factor k. This coverage factor then defines an interval around a measurement value within which the value of the measurand, or true value, is asserted to lie for a desired confidence level (e.g. 95 %). A value of k = 2 is often used to obtain approximate 95 % coverage, although k = 2 will be an underestimate when the standard deviation is estimated from a limited amount of data. An alternative is to use Student’s t-distribution to provide a value for k, but this requires an exact or approximate degrees of freedom (df). This paper explores two different methods of deriving an appropriate k in the case when two variances from an ANOVA (classical or robust) need to be combined to estimate the measurement variance. Simulations show that both methods using the modified coverage factor generally produce a confidence interval much closer to the desired level (e.g. 95 %) when the data are approximately normally distributed. When these confidence intervals do deviate from 95 %, they are consistently conservative (i.e. reported coverage is higher than the nominal 95 %). When outlying values are included at the level of the larger variance component, in some cases the method used for robust ANOVA produces confidence intervals that are very conservative.
Symptoms of selective mutism beyond failure to speak in children and adolescents
Authors: Vogel Felix , Röse Carolin , Schwenck Christina 
Published: March 2024

AbstractUnderstanding the symptoms of a mental disorder is essential for accurate diagnosis or selecting appropriate treatment targets. Despite this, there is a surprising lack of systematic research on the symptoms of selective mutism (SM). While the DSM-5 defines failure to speak as the only core symptom of SM, sparse research suggests that children with SM may experience additional symptoms. Previous studies have been limited in their identification of symptoms of SM, either by using a predefined set of symptoms or by only asking for anxiety-specific symptoms. This may have resulted in important symptoms being overlooked. In this study, we provided n = 86 parents of children and adolescents with SM (3–18 years) with a symptom definition appropriate for the target group. Additionally, parents were asked an open-ended question about any other symptoms they had observed in their children, beyond the failure to speak. The symptoms reported were categorized using qualitative content analysis (QCA) and examined for frequency and association with symptom severity. Ten different symptom categories were identified, with fear, freezing, and avoidance/security behaviors being the most prevalent. On average, parents reported M = 4.74 (SD = 2.37) symptoms from different symptom categories. Only fear was found to be related to symptom severity of SM. As the findings suggest that SM encompasses various symptoms beyond failure to speak, a more sophisticated understanding of SM as a mental disorder with multiple symptoms seems essential. The clinical implications of this are discussed in further detail.
No evidence for a causal contribution of bioavailable testosterone to ADHD in sex-combined and sex-specific two-sample Mendelian randomization studies
Authors: Dinkelbach Lars , Peters Triinu , Grasemann Corinna , Hebebrand Johannes , Hinney Anke , Hirtz Raphael 
Published: March 2024

AbstractThe higher prevalence of attention-deficit/hyperactivity disorder (ADHD) in males raises the question of whether testosterone is implicated in ADHD risk. However, cross-sectional studies did not identify an association between ADHD and testosterone levels. Mendelian randomization (MR) studies can overcome limitations inherent to association studies, especially of reverse causation and residual confounding. In the current study, sex-combined and sex-specific two-sample MR analyses were conducted to address whether testosterone has a causal influence on ADHD risk. Sex-combined as well as sex-specific target-genetic variants for bioavailable testosterone were derived from a large genome-wide association study (GWAS) on up to 382,988 adult white European UK Biobank study participants. In our sex-specific analyses for ADHD, including data from 14,154 males and 4,945 females with ADHD (17,948 and 16,246 controls respectively), no association between bioavailable testosterone and ADHD risk was found, neither in males (inverse-variance weighted (IVW): beta = 0.09, 95%-CI [-0.10, 0.27]) nor in females (IVW: beta=-0.01, 95%-CI [-0.20, 0.19]). However, in the sex-combined analysis, including 38,691 cases and 186,843 controls, genetically predicted bioavailable testosterone was associated with ADHD risk (IVW: beta = 0.24, 95%-CI [0.09, 0.39]). The inclusion of birth weight and/or SHBG as additional variables in multivariable MR analyses did not alter this result. However, when correcting for potential BMI-driven pleiotropy by a multivariable MR study, all effect estimates for testosterone showed non-significant results. Taken together, no robust evidence for a causal effect of bioavailable testosterone on the risk for ADHD was found.
Clinical impact and cost-consequence analysis of ePlex® blood culture identification panels for the rapid diagnosis of bloodstream infections: a single-center randomized controlled trial
Authors: Caspar Yvan , Deves A. , Richarme C. , Le Marechal M. , Ponderand L. , Mounayar A.-L. , Lejeune S. , Arata-Bardet J. , Gallouche M. , Recule C. , Maubon D. , Garnaud C. , Cornet M. , Veloso M. , Chabani B. , Maurin M. , David-Tchouda S. , Pavese P. 
Published: March 2024

Abstract
Purpose
To assess clinical impact and perform cost-consequence analysis of the broadest multiplex PCR panels available for the rapid diagnosis of bloodstream infections (BSI).

Methods
Single-center, randomized controlled trial conducted from June 2019 to February 2021 at a French University hospital with an institutional antimicrobial stewardship program. Primary endpoint was the percentage of patients with optimized antimicrobial treatment 12 h after transmission of positivity and Gram stain results from the first positive BC.

Results
This percentage was significantly higher in the multiplex PCR (mPCR) group (90/105 = 85.7% %, CI95% [77.5 ; 91.8] vs. 68/107 = 63.6%, CI95% [53.7 ; 72.6]; p < 10− 3) at interim analysis, resulting in the early termination of the study after the inclusion of 309 patients. For patients not optimized at baseline, the median time to obtain an optimized therapy was much shorter in the mPCR group than in the control group (6.9 h, IQR [2.9; 17.8] vs. 26.4 h, IQR [3.4; 47.5]; p = 0.001). Early optimization of antibiotic therapy resulted in a non-statistically significant decrease in mortality from 12.4 to 8.8% (p = 0.306), with a trend towards a shorter median length of stay (18 vs. 20 days; p = 0.064) and a non-significant reduction in the average cost per patient of €3,065 (p = 0.15). mPCR identified all the bacteria present in 88% of the samples.

Conclusion
Despite its higher laboratory cost, the use of multiplex PCR for BSI diagnosis leads to early-optimised therapy, seems cost-effective and could reduce mortality and length of stay. Their impact could probably be improved if implemented 24/7.
Repurposing fusidic acid as an antimicrobial against enterococci with a low probability of resistance development
Authors: Abdelmassih Mark M. , Ismail Maha M. , Kashef Mona T. , Essam Tamer 
Published: March 2024

AbstractDrug repurposing constitutes a strategy to combat antimicrobial resistance, by using agents with known safety, pharmacokinetics, and pharmacodynamics. Previous studies have implemented new fusidic acid (FA) front-loading-dose regimens, allowing higher serum levels than those achievable with ordinary doses. As susceptibility breakpoints are affected by serum level, we evaluated the repurposing of FA as an antimicrobial product against enterococci. FA minimum inhibitory concentrations (MICs) against standard enterococci strains; Enterococcus faecalis ATCC 29212 and Enterococcus faecium ATCC 27270 were 2 and 4 µg/mL, respectively. The MIC against 98 enterococcal clinical isolates was ≤ 8 µg/mL; all would be susceptible if categorized according to recalculated breakpoints (≥ 16 µg/mL), based on the serum level achieved using the front-loading regimen. FA administration in vivo, using the BALB/c mouse infection model, significantly reduced bacterial burden by two to three log10 units in the liver and spleen of mice infected with vancomycin-susceptible and -resistant strains. Exposure of the standard enterococcal strains to increasing, but not fixed, FA concentrations resulted in resistant strains (MIC = 128 µg/mL), with thicker cell walls and slower growth rates. Only one mutation (M651I) was detected in the fusA gene of the resistant strain derived from serial passage of E. faecium ATCC 27270, which was retained in the revertant strain after passage in the FA-free medium. In conclusion, FA can be repurposed as an antimicrobial drug against enterococci with a low probability of mutational resistance development, and can be employed for treatment of infections attributable to vancomycin-resistant enterococci.
Exploring the integration of artificial intelligence (AI) and augmented reality (AR) in maritime medicine
Authors: Battineni Gopi , Chintalapudi Nalini , Ricci Giovanna , Ruocco Ciro , Amenta Francesco 
Published: March 2024

AbstractThis narrative literature review has analyzed the integration of artificial intelligence (AI) and augmented reality (AR) in the field of maritime medicine. A comprehensive search was conducted in academic databases using relevant search terms, resulting in the identification of 257 records. After screening for relevance and quality, a final review was conducted on 17 papers. This review highlights the potential applications and benefits of AI and AR in enhancing medical practices and safety measures for seafarers. The integration of AI and AR technologies in maritime medicine shows promise in providing real-time medical assistance, remote consultations, augmented training, and improved diagnostic capabilities. Additionally, AI-driven predictive models can aid in early detection of health issues and support proactive health management onboard ships. Challenges related to data privacy, connectivity at sea, and the need for regulatory frameworks are also discussed. The data analysis reported in this review contributes to a better understanding of the current state and future potential of AI and AR in maritime medicine and provide insights into opportunities for further research and implementation in the maritime industry.