bluuebunny/crossref_metadata_2025_split huggingface dataset:
CaMKIIa+ neurons in the bed nucleus of the stria terminalis modulate pace of natural reward seeking depending on internal state
Authors: Huijgens Patty T. , Heijkoop Roy , Vanderschuren Louk J.M.J. , Lesscher Heidi M.B. , Snoeren Eelke M.S. 
Published: February 2024

AbstractThis study aims to investigate the underlying neurobiological mechanisms that regulate natural reward seeking behaviors, specifically in the context of sexual behavior and sucrose self-administration. The role of CaMKIIa+ neurons in the bed nucleus of the stria terminalis (BNST) was explored using chemogenetic silencing and -stimulation. Additionally, the study examined how these effects interacted with the internal state of the animals. Through detailed behavioral analysis, it was demonstrated that CaMKIIa+ neurons in the BNST play a significant role in the regulation of both sexual behavior and sucrose self-administration. Although the behavioral outcome measures differed between the two behaviors, the regulatory role of the CaMKIIa+ neurons in the BNST was found to converge on the modulation of the pacing of engagement in these behaviors in male rats. Moreover, our study confirmed that the internal physiological state of the animal affects how the BNST modulates these behaviors. These findings suggest that different types of natural rewards may recruit a similar brain circuitry to regulate the display of motivated behaviors. Overall, this research provides valuable insights into the neural mechanisms underlying natural reward seeking and sheds light on the interconnected nature of reward-related behaviors in male rats.
Multifractal Analysis of Measures Arising from Random Substitutions
Authors: Mitchell Andrew , Rutar Alex 
Published: February 2024

AbstractWe study regularity properties of frequency measures arising from random substitutions, which are a generalisation of (deterministic) substitutions where the substituted image of each letter is chosen independently from a fixed finite set. In particular, for a natural class of such measures, we derive a closed-form analytic formula for the $$L^q$$

L
q

-spectrum and prove that the multifractal formalism holds. This provides an interesting new class of measures satisfying the multifractal formalism. More generally, we establish results concerning the $$L^q$$

L
q

-spectrum of a broad class of frequency measures. We introduce a new notion called the inflation word$$L^q$$

L
q

-spectrum of a random substitution and show that this coincides with the $$L^q$$

L
q

-spectrum of the corresponding frequency measure for all $$q \ge 0$$

q
≥
0

. As an application, we obtain closed-form formulas under separation conditions and recover known results for topological and measure theoretic entropy.
Phase-contrast magnetic resonance imaging of intracranial and extracranial blood flow in carotid near-occlusion
Authors: Holmgren Madelene , Henze Alexander , Wåhlin Anders , Eklund Anders , Fox Allan J. , Johansson Elias 
Published: February 2024

Abstract
Purpose
Compare extracranial internal carotid artery flow rates and intracranial collateral use between conventional ≥ 50% carotid stenosis and carotid near-occlusion, and between symptomatic and asymptomatic carotid near-occlusion.

Methods
We included patients with ≥ 50% carotid stenosis. Degree of stenosis was diagnosed on CTA. Mean blood flow rates were assessed with four-dimensional phase-contrast MRI.

Results
We included 110 patients of which 83% were symptomatic, and 38% had near-occlusion. Near-occlusions had lower mean internal carotid artery flow (70 ml/min) than conventional ≥ 50% stenoses (203 ml/min, P < .001). Definite use of ≥ 1 collateral was found in 83% (35/42) of near-occlusions and 10% (7/68) of conventional stenoses (P < .001). However, there were no differences in total cerebral blood flow (514 ml/min vs. 519 ml/min, P = .78) or ipsilateral hemispheric blood flow (234 vs. 227 ml/min, P = .52), between near-occlusions and conventional ≥ 50% stenoses, based on phase-contrast MRI flow rates. There were no differences in total cerebral or hemispheric blood flow, or collateral use, between symptomatic and asymptomatic near-occlusions.

Conclusion
Near-occlusions have lower internal carotid artery flow rates and more collateral use, but similar total cerebral blood flow and hemispheric blood flow, compared to conventional ≥ 50% carotid stenosis.
Outer membrane vesicles as a platform for the discovery of antibodies to bacterial pathogens
Authors: Lei Eric K. , Azmat Aruba , Henry Kevin A. , Hussack Greg 
Published: February 2024

Abstract
Bacterial outer membrane vesicles (OMVs) are nanosized spheroidal particles shed by gram-negative bacteria that contain biomolecules derived from the periplasmic space, the bacterial outer membrane, and possibly other compartments. OMVs can be purified from bacterial culture supernatants, and by genetically manipulating the bacterial cells that produce them, they can be engineered to harbor cargoes and/or display molecules of interest on their surfaces including antigens that are immunogenic in mammals. Since OMV bilayer-embedded components presumably maintain their native structures, OMVs may represent highly useful tools for generating antibodies to bacterial outer membrane targets. OMVs have historically been utilized as vaccines or vaccine constituents. Antibodies that target bacterial surfaces are increasingly being explored as antimicrobial agents either in unmodified form or as targeting moieties for bactericidal compounds. Here, we review the properties of OMVs, their use as immunogens, and their ability to elicit antibody responses against bacterial antigens. We highlight antigens from bacterial pathogens that have been successfully targeted using antibodies derived from OMV-based immunization and describe opportunities and limitations for OMVs as a platform for antimicrobial antibody development.

Key points
• Outer membrane vesicles (OMVs) of gram-negative bacteria bear cell-surface molecules
• OMV immunization allows rapid antibody (Ab) isolation to bacterial membrane targets
• Review and analysis of OMV-based immunogens for antimicrobial Ab development
Tailor-made solvents for microbial carotenoids recovery
Authors: Mussagy Cassamo U. , Hucke Henua U. , Ramos Nataly F. , Ribeiro Helena F. , Alves Mariana B. , Mustafa Ahmad , Pereira Jorge F. B. , Farias Fabiane O. 
Published: February 2024

Abstract
In recent years, microbial carotenoids have emerged as a promising alternative for the pharmaceutical and food industries, particularly in promoting human health due to their potent antioxidant and antimicrobial properties. Microbial carotenoids, particularly those produced by yeast, bacteria, and microalgae, are synthesized intracellularly, requiring the use of solvents for their effective extraction and recovery. The conventional use of toxic volatile organic solvents (VOCs) like hexane, petroleum ether, and dimethyl sulfoxide in the extraction of microbial carotenoids has been common. However, ongoing research is introducing innovative, non-toxic, environmentally friendly tailor-made solvents, such as ionic liquids (IL) and deep eutectic solvents (DES), indicating a new era of cleaner and biocompatible technologies. This review aims to highlight recent advancements in utilizing IL and DES for obtaining carotenoids from microorganisms. Additionally, we explore the utilization of in silico tools designed to determine the solubilities of microbial carotenoids in tailor-made DES and ILs. This presents a promising alternative for the scientific community, potentially reducing the need for extensive experimental screening of solvents for the recovery of microbial carotenoids in the separation processing. According to our expert perspective, both IL and DES exhibit a plethora of exceptional attributes for the recovery of microbial carotenoids. Nevertheless, the current employment of these solvents for recovery of carotenoids is restricted to scientific exploration, as their feasibility for practical application in industrial settings has yet to be conclusively demonstrated.

Key points
• ILs and DES share many tailoring properties for the recovery of microbial carotenoids
• The use of ILs and DES for microbial carotenoid extraction remains driven by scientific curiosity.
• The economic feasibility of ILs and DES is yet to be demonstrated in industrial applications.
Characterization of a recombinant Aspergillus niger GZUF36 lipase immobilized by ionic liquid modification strategy
Authors: Xing Shuqi , Long Jia , Xie Wei , Luo Chaocheng , He Laping , Li Cuiqin , Zeng Xuefeng 
Published: February 2024

Abstract
Enzyme immobilized on magnetic nanomaterials is a promising biocatalyst with efficient recovery under applied magnets. In this study, a recombinant extracellular lipase from Aspergillus niger GZUF36 (PEXANL1) expressed in Pichia pastoris GS115 was immobilized on ionic liquid-modified magnetic nano ferric oxide (Fe3O4@SiO2@ILs) via electrostatic and hydrophobic interaction. The morphology, structure, and properties of Fe3O4@SiO2@ILs and immobilized PEXANL1 were characterized by scanning electron microscopy, Fourier transform infrared spectroscopy, x-ray diffraction, vibration sample magnetometer, and zeta potential analysis. Under optimized conditions, the immobilization efficiency and activity recovery of immobilized PEXANL1 were 52 ± 2% and 122 ± 2%, respectively. The enzymatic properties of immobilized PEXANL1 were also investigated. The results showed that immobilized PEXANL1 achieved the maximum activity at pH 5.0 and 45 °C, and the lipolytic activity of immobilized PEXANL1 was more than twice that of PEXANL1. Compared to PEXANL1, immobilized PEXANL1 exhibited enhanced tolerance to temperature, metal ions, surfactants, and organic solvents. The operation stability experiments revealed that immobilized PEXANL1 maintained 86 ± 3% of its activity after 6 reaction cycles. The enhanced catalytic performance in enzyme immobilization on Fe3O4@SiO2@ILs made nanobiocatalysts a compelling choice for bio-industrial applications. Furthermore, Fe3O4@SiO2@ILs could also benefit various industrial enzymes and their practical uses.

Key points
• Immobilized PEXANL1 was confirmed by SEM, FT-IR, and XRD.
• The specific activity of immobilized PEXANL1 was more than twice that of PEXANL1.
• Immobilized PEXANL1 had improved properties with good operational stability.

Graphical abstract
Enhancing predictability of IDH mutation status in glioma patients at initial diagnosis: a comparative analysis of radiomics from MRI, [18F]FET PET, and TSPO PET
Authors: Kaiser Lena , Quach S. , Zounek A. J. , Wiestler B. , Zatcepin A. , Holzgreve A. , Bollenbacher A. , Bartos L. M. , Ruf V. C. , Böning G. , Thon N. , Herms J. , Riemenschneider M. J. , Stöcklein S. , Brendel M. , Rupprecht R. , Tonn J. C. , Bartenstein P. , von Baumgarten L. , Ziegler S. , Albert N. L. 
Published: February 2024

Abstract
Purpose
According to the World Health Organization classification for tumors of the central nervous system, mutation status of the isocitrate dehydrogenase (IDH) genes has become a major diagnostic discriminator for gliomas. Therefore, imaging-based prediction of IDH mutation status is of high interest for individual patient management. We compared and evaluated the diagnostic value of radiomics derived from dual positron emission tomography (PET) and magnetic resonance imaging (MRI) data to predict the IDH mutation status non-invasively.

Methods
Eighty-seven glioma patients at initial diagnosis who underwent PET targeting the translocator protein (TSPO) using [18F]GE-180, dynamic amino acid PET using [18F]FET, and T1-/T2-weighted MRI scans were examined. In addition to calculating tumor-to-background ratio (TBR) images for all modalities, parametric images quantifying dynamic [18F]FET PET information were generated. Radiomic features were extracted from TBR and parametric images. The area under the receiver operating characteristic curve (AUC) was employed to assess the performance of logistic regression (LR) classifiers. To report robust estimates, nested cross-validation with five folds and 50 repeats was applied.

Results
TBRGE-180 features extracted from TSPO-positive volumes had the highest predictive power among TBR images (AUC 0.88, with age as co-factor 0.94). Dynamic [18F]FET PET reached a similarly high performance (0.94, with age 0.96). The highest LR coefficients in multimodal analyses included TBRGE-180 features, parameters from kinetic and early static [18F]FET PET images, age, and the features from TBRT2 images such as the kurtosis (0.97).

Conclusion
The findings suggest that incorporating TBRGE-180 features along with kinetic information from dynamic [18F]FET PET, kurtosis from TBRT2, and age can yield very high predictability of IDH mutation status, thus potentially improving early patient management.
Toripalimab, a therapeutic monoclonal anti-PD-1 antibody with high binding affinity to PD-1 and enhanced potency to activate human T cells
Authors: Rajasekaran Narendiran , Wang Xiaoguang , Ravindranathan Sruthi , Chin Daniel J , Tseng Su-Yi , Klakamp Scott L , Widmann Kate , Kapoor Varun N , Vexler Vladimir , Keegan Patricia , Yao Sheng , LaVallee Theresa , Khare Sanjay D 
Published: February 2024

AbstractOver the past decade, US Food and Drug Administration (FDA)-approved immune checkpoint inhibitors that target programmed death-1 (PD-1) have demonstrated significant clinical benefit particularly in patients with PD-L1 expressing tumors. Toripalimab is a humanized anti-PD-1 antibody, approved by FDA for first-line treatment of nasopharyngeal carcinoma in combination with chemotherapy. In a post hoc analysis of phase 3 studies, toripalimab in combination with chemotherapy improved overall survival irrespective of PD-L1 status in nasopharyngeal carcinoma (JUPITER-02), advanced non-small cell lung cancer (CHOICE-01) and advanced esophageal squamous cell carcinoma (JUPITER-06). On further characterization, we determined that toripalimab is molecularly and functionally differentiated from pembrolizumab, an anti-PD-1 mAb approved previously for treating a wide spectrum of tumors. Toripalimab, which binds the FG loop of PD-1, has 12-fold higher binding affinity to PD-1 than pembrolizumab and promotes significantly more Th1- and myeloid-derived inflammatory cytokine responses in healthy human PBMCs in vitro. In an ex vivo system employing dissociated tumor cells from treatment naïve non-small cell lung cancer patients, toripalimab induced several unique genes in IFN-γ and immune cell pathways, showed different kinetics of activation and significantly enhanced IFN-γ signature. Additionally, binding of toripalimab to PD-1 induced lower levels of SHP1 and SHP2 recruitment, the negative regulators of T cell activation, in Jurkat T cells ectopically expressing PD-1. Taken together, these data demonstrate that toripalimab is a potent anti-PD-1 antibody with high affinity PD-1 binding, strong functional attributes and demonstrated clinical activity that encourage its continued clinical investigation in several types of cancer.
Caffeine gum improves 5 km running performance in recreational runners completing parkrun events
Authors: Lynn Anthony , Shaw Chloe , Sorsby Anna C. , Ashworth Pippa , Hanif Faysal , Williams Claire E. , Ranchordas Mayur K. 
Published: February 2024

Abstract
Purpose
The purpose of this study was to determine whether caffeine gum improves the performance of recreational runners completing parkruns (weekly, 5 km, mass participant running events).

Methods
Thirty-six recreational runners (M = 31, F = 5; age 33.7 ± 10.7 y; BMI 23.1 ± 2.4 kg/m2) capable of running 5 km in < 25 min were recruited to a study at the Sheffield Hallam parkrun, UK. Runners were block randomized into one of three double-blind, placebo-controlled, cross-over intervention trials with caffeine gum as the treatment (n = 6 per intervention trial) or into one of three non-intervention trials that ran concurrently with the intervention trials (n = 6 per non-intervention trial). Changes in conditions across different parkruns were adjusted for using data from the non-intervention trials. Runners in the randomized cross-over intervention trials chewed gum supplying 300 mg of caffeine or a placebo gum for 5 min, starting 30 min before each parkrun.

Results
Caffeine gum improved 5 km parkrun performance by a mean of 17.28 s (95% CI 4.19, 30.37; P = 0.01). Adjustment for environmental conditions using data from the non-intervention trials attenuated the statistical significance (P = 0.04). Caffeine gum also decreased RPE by 1.21 (95% CI 0.30, 2.13; P = 0·01) units relative to placebo.

Conclusions
A 300 mg dose of caffeine supplied in chewing gum improved the performance of recreational runners completing 5 km parkruns by an average of 17 s.

Trial Registration
The study was registered at ClinicalTrials.gov: NCT02473575 before recruitment commenced.
Comparison of five different fluoroscopic methods for identifying the MPFL femoral footprint
Authors: Emre Tuluhan Yunus , Cetin Hakan , Selcuk Huseyin , Kilic Koray Kaya , Aykanat Faruk , Sarikcioglu Levent , Kose Ozkan 
Published: February 2024

Abstract
Purpose
The success of medial patellofemoral ligament (MPFL) reconstruction is closely linked to the precise positioning of the femoral tunnel. Intraoperative fluoroscopy is commonly utilized to identify the MPFL footprint. This study aimed to ascertain the most accurate fluoroscopic method among the five previously described methods used to determine the MPFL femoral footprint.

Materials and methods
Using 44 well-preserved dry femur bones, the MPFL femoral insertion site was demarcated using anatomical bony landmarks, namely the center of the saddle sulcus between the medial epicondyle, adductor tubercle and gastrocnemius tubercle. Fluoroscopic true lateral knee images were acquired and measurements taken, referencing established methods by Schottle et al., Redfern et al., Wijdicks et al., Barnett et al., and Kaipel et al. The distance between anatomic and fluoroscopic MPFL footprints was then measured on digital fluoroscopic images. The accuracy of the locations was compared using a margin of error of 5 and 7 mm.

Results
The Schottle method consistently emerged superior, showcasing the smallest mean distance (3.2 ± 1.2 mm) between the anatomic and radiographic MPFL footprints and a high in-point detection rate of 90.9% under 5 mm criteria. While the Redfern method displayed perfect accuracy (100%) within the 7 mm criteria, the Schottle method also performed 97.7% accuracy.

Conclusions
For intraoperative identification of the MPFL footprint using fluoroscopy, the Schottle method is the most consistent and accurate among the assessed methods. Thus, its accuracy in detecting the MPFL footprint makes it recommended for MPFLR to ensure optimal outcomes.

Level of evidence
Level IV, cadaveric study.
Mutational spectrum in patients with dominant non-syndromic hearing loss in Austria
Authors: Frohne Alexandra , Vrabel Sybille , Laccone Franco , Neesen Juergen , Roesch Sebastian , Dossena Silvia , Schoefer Christian , Frei Klemens , Parzefall Thomas 
Published: February 2024

Abstract
Purpose
Hearing loss (HL) is often monogenic. The clinical importance of genetic testing in HL may further increase when gene therapy products become available. Diagnoses are, however, complicated by a high genetic and allelic heterogeneity, particularly of autosomal dominant (AD) HL. This work aimed to characterize the mutational spectrum of AD HL in Austria.

Methods
In an ongoing prospective study, 27 consecutive index patients clinically diagnosed with non-syndromic AD HL, including 18 previously unpublished cases, were analyzed using whole-exome sequencing (WES) and gene panels. Novel variants were characterized using literature and bioinformatic means. Two additional Austrian medical centers provided AD HL mutational data obtained with in-house pipelines. Other Austrian cases of AD HL were gathered from literature.

Results
The solve rate (variants graded as likely pathogenic (LP) or pathogenic (P)) within our cohort amounted to 59.26% (16/27). MYO6 variants were the most common cause. One third of LP/P variants were truncating variants in haploinsufficiency genes. Ten novel variants in HL genes were identified, including six graded as LP or P. In one cohort case and one external case, the analysis uncovered previously unrecognized syndromic presentations.

Conclusion
More than half of AD HL cases analyzed at our center were solved with WES. Our data demonstrate the importance of genetic testing, especially for the diagnosis of syndromic presentations, enhance the molecular knowledge of genetic HL, and support other laboratories in the interpretation of variants.
Assessment of Schlemm’s canal with swept-source optical coherence tomography in Graves’ ophthalmopathy
Authors: Gün Raziye Dönmez , Yazıcıoğlu Titap , Oklar Murat , Gökkaya Naile 
Published: February 2024

Abstract
Purpose
To evaluate the Schlemm’s canal (SC) parameters obtained by swept-source optical coherence tomography (OCT) different in Graves’ ophthalmopathy (GO) eyes compared to healthy eyes.

Methods
This cross-sectional observational study evaluated 64 eyes of 32 GO cases and 56 eyes of 28 healthy controls. The study was conducted between October 2020 and June 2021. SC images were obtained from the temporal limbus of individuals using swept-source OCT. SC length (SCL) and SC area (SCA) were measured. The relationship between SC parameters in the patient group and intraocular pressure (IOP), retinal nerve fiber layer (RNFL) thickness, Graves’ disease (GD) duration, and clinical activity score (CAS) was evaluated.

Results
In the GO group, 64 eyes of 32 patients were evaluated, and in the age and gender-matched healthy control group, 56 eyes of 28 individuals were assessed. SC images from 4 eyes of 4 patients in the patient group and 1 eye of 1 patient in the control group were not clear, preventing SCL and SCA measurements for these eyes. SCL and SCA measurements were found to be lower, and IOP and Hertel values were higher in the GO group compared to the healthy controls. However, no significant correlation was observed between SCL and SCA with IOP, RNFL thickness, GD duration, GO duration, or CAS in the GO group. In the GO group, the mean value of SCA was found to be higher in eyes with glaucoma or OHT compared to those without.

Conclusion
These findings indicate that SC in GO-affected eyes is shorter and has a smaller area than in healthy individuals. Additionally, higher IOP and Hertel values were observed in the GO group compared to healthy controls. This study suggests that assessing SC using anterior segment OCT could provide valuable insights into the regulation of IOP and the development of glaucoma in GO-affected eyes.