bluuebunny/crossref_metadata_2025 huggingface dataset:
Immune evasion by Cryptococcus gattii in vaccinated mice coinfected with C. neoformans
Authors: Hester Maureen M. , Carlson Diana , Lodge Jennifer K. , Levitz Stuart M. , Specht Charles A.
Published: February 2024

Cryptococcus neoformans and C. gattii, the etiologic agents of cryptococcosis, cause over 100,000 deaths worldwide every year, yet no cryptococcal vaccine has progressed to clinical trials. In preclinical studies, mice vaccinated with an attenuated strain of C. neoformans deleted of three cryptococcal chitin deacetylases (Cn-cda1Δ2Δ3Δ) were protected against a lethal challenge with C. neoformans strain KN99. While Cn-cda1Δ2Δ3Δ extended the survival of mice infected with C. gattii strain R265 compared to unvaccinated groups, we were unable to demonstrate fungal clearance as robust as that seen following KN99 challenge. In stark contrast to vaccinated mice challenged with KN99, we also found that R265-challenged mice failed to induce the production of protection-associated cytokines and chemokines in the lungs. To investigate deficiencies in the vaccine response to R265 infection, we developed a KN99-R265 coinfection model. In unvaccinated mice, the strains behaved in a manner which mirrored single infections, wherein only KN99 disseminated to the brain and spleen. We expanded the coinfection model to Cn-cda1Δ2Δ3Δ-vaccinated mice. Fungal burden, cytokine production, and immune cell infiltration in the lungs of vaccinated, coinfected mice were indicative of immune evasion by C. gattii R265 as the presence of R265 neither compromised the immunophenotype established in response to KN99 nor inhibited clearance of KN99. Collectively, these data indicate that R265 does not dampen a protective vaccine response, but rather suggest that R265 remains largely undetected by the immune system.
Immune priming modulates Galleria mellonella and Pseudomonas entomophila interaction. Antimicrobial properties of Kazal peptide Pr13a
Authors: Sułek Michał , Kordaczuk Jakub , Mak Paweł , Śmiałek-Bartyzel Justyna , Hułas-Stasiak Monika , Wojda Iwona
Published: February 2024

Galleria mellonella larvae repeatedly infected with Pseudomonas entomophila bacteria re-induced their immune response. Its parameters, i.e. the defence activities of cell-free hemolymph, the presence and activity of antimicrobial peptides, and the expression of immune-relevant genes were modulated after the re-challenge in comparison to non-primed infected larvae, resulting in better protection. No enhanced resistance was observed when the larvae were initially infected with other microorganisms, and larvae pre-infected with P. entomophila were not more resistant to further infection with other pathogens. Then, the peptide profiles of hemolymph from primed- and non-primed larvae infected with P. entomophila were compared by quantitative RP-HPLC (Reverse Phase - High Performance Liquid Chromatography). The level of carbonic anhydrase, anionic peptide-1, proline peptide-2, and finally, unknown so far, putative Kazal peptide Pr13a was higher in the primed infected animals than in the larvae infected with P. entomophila for the first time. The expression of the Pr13a gene increased two-fold after the infection, but only in the primed animals. To check whether the enhanced level of Pr13a could have physiological significance, the peptide was purified to homogeneity and checked for its defence properties. In fact, it had antibacterial activity: at the concentration of 15 µM and 7.5 µM it reduced the number of P. entomophila and Bacillus thuringiensis CFU, respectively, to about 40%. The antibacterial activity of Pr13a was correlated with changes observed on the surface of the peptide-treated bacteria, e.g. surface roughness and adhesion force. The presented results bring us closer to finding hemolymph constituents responsible for the effect of priming on the immune response in re-infected insects.
Estimating three-dimensional current fields in the Yeosu Bay using coastal acoustic tomography system
Authors: Hwang Yerin , Lee Eun-Joo , Song Hajin , Kim Byoung-Nam , Ha Ho Kyung , Choi Yohan , Kwon Jae-Il , Park Jae-Hun
Published: February 2024

Observation of current speeds in coastal seas is crucial because it can provide useful information for ship operations, fishing activities, and rapid responses to marine disasters. Coastal acoustic tomography (CAT) is a technology that can continuously monitor environmental changes such as current velocity and water temperature using reciprocal acoustic signals between CAT stations in coastal seas. This technology is different from traditional pointwise or intermittent sectional observations in that it can produce time-varying two- or three-dimensional current fields. The results of previous studies using CAT systems have been limited to reproducing horizontal maps of depth-averaged two-dimensional current fields. Utilizing results from a high-resolution coastal ocean model, this study developed a novel technique for estimating three-dimensional (3-D) current fields by combining the inverse method with an artificial intelligence (AI) model. Following three steps are the procedure for the test of estimating the 3-D current fields. First, utilizing the ray tracing model ‘Bellhop,’ reciprocal travel times among five CAT stations using the coastal ocean model outputs are computed. These five stations correspond to the locations where in-situ CAT systems were established for continuous monitoring of current changes in Yeosu Bay, Korea. Subsequently, the range-averaged currents at the five layers were estimated by incorporating this travel time difference data into an AI model trained using the same coastal ocean model outputs. Finally, the inverse method is applied to each layer to estimate the 3-D current fields. The validation results revealed that the newly developed method performed well in both summer and winter. Time-varying two-layer-like current fields were reasonably produced, occasionally revealing an out-of-phase relationship between the upper and lower layers depending on the tidal phases. This method yielded average root-mean-squared errors of less than 4 cm/s on six simulation paths for acoustic signal propagation. Furthermore, when the same method was applied to in-situ CAT observations, the average correlation coefficient (R) of the along-channel current of each layer was found to be approximately 0.9 or higher. These results suggest that this novel method can be effectively applied to the continuous monitoring of 3-D current fields in coastal seas using a CAT system.
Comparison of ruminal microbiota, IL-1β gene variation, and tick incidence between Holstein × Gyr and Holstein heifers in grazing system
Authors: Quirino Daiana Francisca , Marcondes Marcos Inácio , Oliveira Kellen Ribeiro de , Guimarães Simone Elisa Facioni , Silva Juliana Soares da , Suen Garret , Rossi Letícia Elisa , Cunha Camila Soares , Mantovani Hilario Cuquetto , Rotta Polyana Pizzi
Published: February 2024

Introduction

The variation in bacterial communities among breeds has been previously reported and may be one of the reasons why Holstein × Gyr dairy heifers have better development in grazing systems in tropical conditions. This study aimed to explore the ruminal microbiota composition, the IL-1β gene variation, tick incidence, and blood parameters of Holstein × Gyr (½ Holstein × ½ Gyr) and Holstein heifers grazing intensely managed Guinea grass (Panicum maximum Jacq. cv. Mombaça).

Methods

Sixteen heifers were divided into two groups consisting of 8 Holstein × Gyr and 8 Holstein heifers. The experimental period was comprised of 3 periods of 21 days. Ruminal samples were taken via the stomach tube technique. The sequencing of the V4 hypervariable region of the 16S rRNA gene was performed using the Illumina MiSeq platform. Counting and collection of ticks were conducted each 21 days. Blood and skeletal muscle tissue biopsies were performed at the end of the experiment.

Results

Firmicutes were the most abundant phyla present in both breed rumen samples and Bacteroidota showed differences in relative abundance between breed groups, with greater values for Holstein heifers (p < 0.05 with FDR correction). The 10 most abundant unique OTUs identified in each breed included several OTUs of the genus Prevotella. Holstein heifers had a greater tick count and weight (9.8 ticks/animal and 1.6 g/animal, respectively) than Holstein × Gyr (2.56 ticks/animal and 0.4 g/animal, respectively). We found nucleotide substitutions in the IL-1β gene that might be related to adaptation and resistance phenotypes to tick infestation in Holstein × Gyr heifers. Blood concentrations of urea, albumin, insulin-like growth factor 1, triiodothyronine, and thyroxine were greater in Holstein × Gyr than in Holstein heifers.

Conclusion

Adaptations in Holstein × Gyr heifers such as ruminal microbiota, tick resistance, nucleotide substitutions in IL-1β gene, and hormone concentration suggest a better energy metabolism and thermoregulation resulting in better performance in tropical grazing systems.
Discovery and vertical transmission analysis of Dabieshan Tick Virus in Haemaphysalis longicornis ticks from Chengde, China
Authors: Xu Xiaofeng , Gao Zhihua , Wu Youhong , Yin Hong , Ren Qiaoyun , Zhang Jie , Liu Yongsheng , Yang Shunli , Bayasgalan Chimedtseren , Tserendorj Ariunaa , Yang Xiaolong , Chen Ze
Published: February 2024

Introduction

Ticks are important blood-sucking ectoparasites that can transmit various pathogens, posing significant threats to the wellbeing of humans and livestock. Dabieshan tick virus (DBTV) was initially discovered in 2015 in Haemaphysalis longicornis ticks from the Dabieshan mountain region in Hubei Province, China. In recent years, DBTV has been discovered in various regions of China, including Shandong, Zhejiang, Liaoning, Hubei, Yunnan, and Guizhou Provinces. However, the researches on tick-borne transmission of DBTV are scarce.

Methods

This study utilized the small RNA sequencing (sRNA-seq) method to identify tick-associated viruses in ticks collected from Chengde in Hebei Province and Yongcheng in Henan Province, leading to the discovery of a new DBTV strain in Hebei. The complete coding genome of DBTV Hebei strain was obtained through RNA-seq and Sanger sequencing. Furthermore, the transmission experiment of DBTV in H. longicornis was examined in laboratory for the first time.

Results

DBTV was detected in newly molted adult H. longicornis ticks collected in Chengde, Hebei Province. Additionally, DBTV was also detected in both unfed nymphs and engorged females of H. longicornis collected from Chengde, with a positive rate of 20% and 56.25%, respectively. The complete coding genome of DBTV (OP682840 and OP716696) were obtained, and phylogenetic analysis revealed that the DBTV Hebei strain clustered with previously reported DBTV strains. Furthermore, this virus was observed in engorged females, eggs, and larvae of the subsequent generation.

Discussion

It is necessary to expand the scope of DBTV investigation, particularly in northern China. This study demonstrated that DBTV can be transmitted from engorged females to larvae of the next generation. Moreover, the detection of DBTV in unfed nymphs and adults (which moulted from engorged nymphs) collected from the filed of Chengde suggests that H. longicornis serves as a potential transmission host and reservoir for DBTV through transstadial and transovarial transmission. However, there remains a lack of research on the isolation and pathogenicity of DBTV, highlighting the need for further studies to mitigate potential harm to the health of animals and humans.
Dissimilarities of neural representations of extinction trials are associated with extinction learning performance and renewal level
Authors: Lissek Silke , Tegenthoff Martin
Published: February 2024

Introduction

Renewal of extinguished responses is associated with higher activity in specific extinction-relevant brain regions, i.e., hippocampus (HC), inferior frontal gyrus (IFG), and ventromedial PFC (vmPFC). HC is involved in processing of context information, while IFG and vmPFC use such context information for selecting and deciding among competing response options. However, it is as yet unknown to what extent trials with changed versus unchanged outcome, or extinction trials that evoke renewal (i.e., extinction context differs from acquisition and test context: ABA trials) and trials that do not (i.e., same context in all phases: AAA trials) are represented differentially in extinction-relevant brain regions.

Methods

In this study, we applied representational similarity analysis (RSA) to determine differences in neural representations of these trial types and their relationship to extinction error rates and renewal level.

Results

Overall, individuals with renewal (REN) and those without (NoREN) did not differ significantly in their discrimination levels between ABA and AAA extinction trials, with the exception of right posterior HC, where REN exhibited more pronounced context-related discrimination. In addition, higher dissimilarity of representations in bilateral posterior HC, as well as in several IFG regions, during extinction learning was linked to lower ABA renewal rates. Both REN and NoREN benefitted from prediction error feedback from ABA extinction errors for context- and outcome-related discrimination of trials in IFG, vmPFC, and HC, but only the NoREN group also benefitted from error feedback from AAA extinction errors.

Discussion

Thus, while in both groups the presence of a novel context supported formation of distinct representations, only in NoREN the expectancy violation of the surprising change of outcome alone had a similar effect. In addition, only in NoREN context-related discrimination was linked to error feedback in vmPFC. In summary, the findings show that context- and outcome-related discrimination of trials in HC, vmPFC, and IFG is linked to extinction learning errors, regardless of renewal propensity, and at the same time point towards differential context processing strategies in REN and NoREN. Moreover, better discrimination of context-related trials during extinction learning promotes less renewal during extinction recall, suggesting that renewal may be related to suboptimal context-related trial discrimination.
Dorsal CA1 lesions of the hippocampus impact mating tactics in prairie voles by shifting non-monogamous males’ use of space to resemble monogamous males
Authors: Sailer Lindsay L. , Finton Caitlyn J. , Patel Pooja P. , Bogdanowicz Steven M. , Ophir Alexander G.
Published: February 2024

Alternative mating tactics within mating systems are characterized by discrete patterns of spatio-temporal overlap with same-and opposite-sex conspecifics and mating-relevant outcomes. Socially monogamous “residents” maintain relatively small home range sizes, have territories that almost exclusively overlap with their mating partners, and are more likely to produce offspring than non-bonded “wandering” conspecifics. Because mating tactics appear to be so closely tied to patterns of space use, differences in spatial cognitive abilities might differentially impact individual males’ decisions to adopt a particular mating tactic and/or how efficient they are within their chosen mating tactic. Yet few studies have considered how the hippocampus, a brain region important for encoding cognitive maps and for processing contextual information, might impact how individuals adopt mating tactics or the spatio-temporal behaviors closely associated with them. We assessed the impact of lesions to the dorsal CA1 (dCA1) region of the hippocampus on male prairie vole space use, reproductive success, and mating tactics in semi-natural outdoor field conditions. Interestingly, dCA1 lesions did not impact the proportion of males that adopted resident or wandering mating tactics, and dCA1 lesions did not impact a male’s ability to form a pair bond in the lab. In contrast, we found that lesioning the dCA1 shifted the home range size of reproductively successful and unsuccessful males. Furthermore, we found that patterns of space use among residents were unaffected by dCA1 lesions, whereas wanderers with dCA1 lesions showed pronounced reductions of their space use habits and resembled non-lesioned residents. Collectively, our study supports the hypothesis that wanderer male prairie voles rely on dCA1-mediated spatial cognition to navigate their world in a way that resident males do not. Such differences might have implications for how individuals efficiently attract and defend mates, obtain resources, defend territories, and outcompete rivals.
Treatment and outcome analysis of patients with ruptured distal anterior cerebral artery aneurysms: a multicenter real-world study
Authors: Zhu Xiaowei , He Zhen , Wu Zhuolin , Li Yang , Zhao Yan , Wang Bangyue , Zhang Nai , Huang Qiang , Yang Tao , Yang Minghao , Li Jia , Yang Xinyu , Wang Yanzhou , Zhang Zhongyuan
Published: February 2024

Objective

To reveal the safety and efficacy of clipping and coiling in patients with ruptured distal anterior cerebral artery aneurysms (DACAA) and to calculate the risk factors affecting the two-year survival rate in follow-up patients.

Methods

A retrospective study was conducted on the data of 140 patients (21 were lost to follow-up) with DACAA rupture who were treated by neurosurgery at 12 medical centers over a 2-year period, from January 2017 to December 2020. Univariate analysis was used to examine factors contributing to poor patient prognosis and to compare the prognosis of coiling and clipping treatments. Survival analysis was employed to compare survival rates between coiling and clipping, and risk factors affecting patient survival were analyzed using multivariate Cox regression analysis.

Results

Out of 140 patients with ruptured DACAA, 80 (57.1%) were male, and 60 (42.9%) were female. A total of 111 (79.3%) patients were classified under Hunt-Hess scale grades I-III, while 95 (67.9%) were graded I-III according to the WFNs classification. Among them, 63 (45%) were treated with clipping, and 77 (55%) underwent coiling. Within 2 years of discharge from the hospital, 31 (59.6%) patients who underwent clipping and 54 (80.6%) who underwent coiling had a good prognosis. Multivariate Cox regression analysis revealed that only WFNs classification (I-III) was a protective factor influencing the 2-year survival of patients with ruptured DACAA.

Conclusion

In the reality of medical practice, neurosurgeons are more likely to choose clipping as the treatment for cases with WFNs classification than or equal to III. There was no difference between clipping and coiling in the two-year prognosis at discharge. High priority should be given to DACAA cases with WFNs grading (I-III), as better outcomes can be achieved. The sample size will continue to be enlarged in the future to obtain more accurate findings. Abstracts for reviews, technical notes, and historical vignettes do not need to be separated into sections. They should begin with a clear statement of the paper’s purpose followed by appropriate details that support the authors’ conclusion(s).
Localized radiotherapy of solid tumors using radiopharmaceutical loaded implantable system: insights from a mathematical model
Authors: Piranfar Anahita , Souri Mohammad , Rahmim Arman , Soltani Madjid
Published: February 2024

Introduction

Computational models yield valuable insights into biological interactions not fully elucidated by experimental approaches. This study investigates an innovative spatiotemporal model for simulating the controlled release and dispersion of radiopharmaceutical therapy (RPT) using 177Lu-PSMA, a prostate-specific membrane antigen (PSMA) targeted radiopharmaceutical, within solid tumors via a dual-release implantable delivery system. Local delivery of anticancer agents presents a strategic approach to mitigate adverse effects while optimizing therapeutic outcomes.

Methods

This study evaluates various factors impacting RPT efficacy, including hypoxia region extension, binding affinity, and initial drug dosage, employing a novel 3-dimensional computational model. Analysis gauges the influence of these factors on radiopharmaceutical agent concentration within the tumor microenvironment. Furthermore, spatial and temporal radiopharmaceutical distribution within both the tumor and surrounding tissue is explored.

Results

Analysis indicates a significantly higher total concentration area under the curve within the tumor region compared to surrounding normal tissue. Moreover, drug distribution exhibits notably superior efficacy compared to the radiation source. Additionally, low microvascular density in extended hypoxia regions enhances drug availability, facilitating improved binding to PSMA receptors and enhancing therapeutic effectiveness. Reductions in the dissociation constant (KD) lead to heightened binding affinity and increased internalized drug concentration. Evaluation of initial radioactivities (7.1×107, 7.1×108, and 7.1×109 [Bq]) indicates that an activity of 7.1×108 [Bq] offers a favorable balance between tumor cell elimination and minimal impact on normal tissues.

Discussion

These findings underscore the potential of localized radiopharmaceutical delivery strategies and emphasize the crucial role of released drugs relative to the radiation source (implant) in effective tumor treatment. Decreasing the proximity of the drug to the microvascular network and enhancing its distribution within the tumor promote a more effective therapeutic outcome. The study furnishes valuable insights for future experimental investigations and clinical trials, aiming to refine medication protocols and minimize reliance on in vivo testing.
The patient perspective on sirolimus for epithelioid hemangioendothelioma (EHE): results of a community survey highlighting the importance of equitable access to treatments
Authors: Robinson Denise , Leonard Hugh , Baldi Giacomo Giulio , Tap William D. , Jones Robin L. , Stacchiotti Silvia , Pantziarka Pan
Published: February 2024

Background

Epithelioid hemangioendothelioma (EHE) is an ultra-rare, vascular sarcoma with clinical presentation ranging from an indolent to an aggressive form. Over 50% of patients present with metastatic disease, requiring systemic therapy, although no systemic therapies are specifically approved for EHE. Retrospective evidence supports the activity of mTOR inhibitors (e.g. sirolimus), although available only off-label. EHE patients and advocates are therefore working to support approval of effective treatments by collecting data on patient perspectives and experiences.

Materials and methods

In February 2023, the EHE Rare Cancer Charity (UK) and The EHE Foundation (US), with other advocates, conducted a survey of perspectives and experiences of EHE patients regarding the use and accessibility of sirolimus. The survey consisted of 20 questions designed for individuals undergoing treatment, those who had been treated, or had never been treated with the drug. Widely promoted within the patient community, the online survey categorized patients into three cohorts for the analysis: liver transplant patients, non-transplant patients who had ever taken sirolimus and sirolimus-naïve non-transplant patients.

Results

The survey evaluated data from 129 patient responses from 21 countries, mostly from USA, UK, Australia, and Canada (70%). The liver transplant, sirolimus and non-sirolimus cohorts were 16%, 25% and 59%, respectively. In the sirolimus group 66% reported treatment durations exceeding one year, with 16% exceeding five years, indicating the drug’s efficacy. In the non-sirolimus group, the drug was not available for 42% and for 11% sirolimus was available but not selected for treatment because of its off-label status. Overall, 87% of all patients across all cohorts expressed the importance of the drug’s availability as hugely or very important.

Conclusion

The survey responses highlight the activity of sirolimus for EHE and the importance of securing a label extension for the drug delivering equitable access to this treatment for patients.
The combination use of inclisiran and statins versus statins alone in the treatment of dyslipidemia in mainland China: a cost-effectiveness analysis
Authors: Zhou Wenjing , Liang Zhuoru , Lou Xiaohuan , Wang Nansong , Liu Xinyu , Li Ruoxi , Pai Pearl
Published: February 2024

Objective: Statin is well-established as a classical lipid-lowering drug, and its cost has reduced considerably in the past years. Inclisiran is a new and effective lipid-lowering drug given as a subcutaneous injection at 6-month intervals. This study aims to evaluate the cost-effectiveness of the combination use of inclisiran and statin versus statin alone for dyslipidemia in the mainland China population.

Methods: The Markov decision-making model was used, and the clinical data and real-world data were collected at the University of Hong Kong–Shenzhen Hospital (HKU-SZH). Patients with cardiovascular disease (CVD) and blood lipid levels above the target on statin therapy were included as the target population and analyzed for cardiovascular events, future medical expenses, and the calculation made for the total life cost, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). Sensitivity analysis was conducted to evaluate the influence of parameter uncertainty on the base-case analysis results.

Results: If inclisiran was priced at Chinese renminbi (RMB) 20,000.00 (USD 2,973.49) per injection, patients in the inclisiran and statin group would incur an incremental cost of RMB 449,233.56 (USD 66,789.60) compared with the statin group, and they would obtain 0.21 more QALYs in their life cycle. The subsequent ICER of RMB 2,127,756.78 (USD 316,343.32)/QALY was significantly higher than the willingness-to-pay (WTP) threshold of 3 times the per capita GDP of China, which was RMB 257,094.00 (USD 38,223.33)/QALY, suggesting that the combined use of inclisiran and statin was not cost-effective. If the price of inclisiran were reduced to RMB 2,500.00 (USD 371.69)/injection, the ICER of patients in the inclisiran and statin group would become RMB 257,790.63 (USD 38,326.91)/QALY, which is slightly lower than the WTP threshold of 3 times the per capita GDP of China, indicating that the combined use of inclisiran and statin would be cost-effective.

Conclusion: If inclisiran is priced at RMB 20,000.00 (USD 2,973.49)/injection, then the combined use of inclisiran and statins is not cost-effective compared with statin alone. It will be economical only if the price of inclisiran is reduced by more than 88%.
Development of fullerene acceptors and the application of non-fullerene acceptors in organic solar cells
Authors: Du Wen-Shuo , Wang Gong , Li Yun-Fei , Yu Yu
Published: February 2024

Organic solar cells (OSCs) enjoy a huge market and public attention as an emerging renewable and clean energy source due to their accessibility, sustainability, translucency, good flexibility, non-toxicity, and low preparation cost. However, the choice of an acceptor material is now the pivotal factor restricting the development of OSCs. To continuously improve stability and increase power conversion efficiency (PCE) for better performance, high-performance acceptor materials are an important part of enabling OSCs. From fullerenes and their derivatives and non-fullerenes, we sum up the latest research progress on high-performance acceptor materials for OSCs and then introduce the synthesis methods of non-fullerenes. The latest strategies to enhance the performance of organic solar cells and the wide range of applications of non-fullerene acceptors (NFAs) on different OSCs are also discussed. In addition, challenges faced by OSCs in improving their performance and the prospects for future development are revealed, providing new ideas for designing the next generation of high-performance OSCs.
Swimming behavior indicates stress and adaptations to exercise
Authors: Yu Sen , Liu Lantao , Li Min , He Siyan , Hu Yang , Sun Shichao , Yan Yizhen , Zhao Fangfang , Cheng Xiangrong , Li Jia , Gao Feng , Liu Yong , Zhang Xing
Published: February 2024

Introduction: Behaviors of swimming rodents are not uniform, exhibiting large variations, which may underlie the individual differences in swimming exercise-induced benefits. The study aimed to monitor individualized swimming behavior and evaluate its biological significance.

Methods: A swimming tank which can monitor individualized rodent swimming behavior during exercise was established. A total of 45 mice were subjected to swimming training for 1 month (1 h per day) and the swimming behaviors of each mouse were recorded.

Results: The swimming behaviors of mice displayed considerable variations in aspects of distance, velocity, and area preference. For example, nearly one-third of mice preferred to swim in central area and most of the mice exhibited an even area distribution. Long-term exercise training improved cardiac systolic function and decreased blood pressure in mice, but hardly changed swimming behaviors. Analyses of the relationship between swimming behavior and cardiovascular adaptations to exercise training revealed that swimming behavior indicated the biological effects of swimming training. Specifically, mice which preferred swimming at the central zone or were trainable in behavior during 1-month training exhibited better outcomes in cardiac function and blood pressure post long-term exercise. Mechanistically, a centralized swimming behavior indicated a smaller stress during exercise, as evidenced by a milder activation of hypothalamic–pituitary–adrenal axis.

Discussion: These results suggest that swimming behavior during training indicates individualized adaptations to long-term exercise, and highlight a biological significance of swimming behavior monitoring in animal studies.
Vitamin E biofortification: enhancement of seed tocopherol concentrations by altered chlorophyll metabolism
Authors: Qin Ping , Chen Peng , Zhou Yuanwei , Zhang Wei , Zhang Yunyun , Xu Jingjing , Gan Lu , Liu Yingnan , Romer Jill , Dörmann Peter , Cahoon Edgar B. , Zhang Chunyu
Published: February 2024

Homogentisate Phytyltransferase (HPT) catalyzes condensation of homogentisate (HGA) and phytyl diphosphate (PDP) to produce tocopherols, but can also synthesize tocotrienols using geranylgeranyl diphosphate (GGDP) in plants engineered for deregulated HGA synthesis. In contrast to prior tocotrienol biofortification efforts, engineering enhanced tocopherol concentrations in green oilseeds has proven more challenging due to the integral role of chlorophyll metabolism in supplying the PDP substrate. This study show that RNAi suppression of CHLSYN coupled with HPT overexpression increases tocopherol concentrations by >two-fold in Arabidopsis seeds. We obtained additional increases in seed tocopherol concentrations by engineering increased HGA production via overexpression of bacterial TyrA that encodes chorismate mutase/prephenate dehydrogenase activities. In overexpression lines, seed tocopherol concentrations increased nearly three-fold, and resulted in modest tocotrienol accumulation. We further increased total tocochromanol concentrations by enhancing production of HGA and GGDP by overexpression of the gene for hydroxyphenylpyruvate dioxygenase (HPPD). This shifted metabolism towards increased amounts of tocotrienols relative to tocopherols, which was reflected in corresponding increases in ratios of GGDP/PDP in these seeds. Overall, our results provide a theoretical basis for genetic improvement of total tocopherol concentrations in green oilseeds (e.g., rapeseed, soybean) through strategies that include seed-suppression of CHLSYN coupled with increased HGA production.
Neuropsychological assessment of aggressive offenders: a Delphi consensus study
Authors: Hutten Juliette C. , van Horn Joan E. , Hoppenbrouwers Sylco S. , Ziermans Tim B. , Geurts Hilde M. ,   The Forensic Neuropsychology Consortium
Published: February 2024

Objective

This study explores the intricate relationship between cognitive functioning and aggression, with a specific focus on individuals prone to reactive or proactive aggression. The purpose of the study was to identify important neuropsychological constructs and suitable tests for comprehending and addressing aggression.

Methods

An international panel of 32 forensic neuropsychology experts participated in this three-round Delphi study consisting of iterative online questionnaires. The experts rated the importance of constructs based on the Research Domain Criteria (RDoC) framework. Subsequently, they suggested tests that can be used to assess these constructs and rated their suitability.

Results

The panel identified the RDoC domains Negative Valence Systems, Social Processes, Cognitive Systems and Positive Valence Systems as most important in understanding aggression. Notably, the results underscore the significance of Positive Valence Systems in proactive aggression and Negative Valence Systems in reactive aggression. The panel suggested a diverse array of 223 different tests, although they noted that not every RDoC construct can be effectively measured through a neuropsychological test. The added value of a multimodal assessment strategy is discussed.

Conclusions

This research advances our understanding of the RDoC constructs related to aggression and provides valuable insights for assessment strategies. Rather than suggesting a fixed set of tests, our study takes a flexible approach by presenting a top-3 list for each construct. This approach allows for tailored assessment to meet specific clinical or research needs. An important limitation is the predominantly Dutch composition of the expert panel, despite extensive efforts to diversify.
Affective norms for 501 Chinese words from three emotional dimensions rated by depressive disorder patients
Authors: Xu Xinyue , An Fei , Wu Shengjun , Wang Hui , Kang Qi , Wang Ying , Zhu Ting , Zhang Bing , Huang Wei , Liu Xufeng , Wang Xiuchao
Published: February 2024

Introduction

Emotional words are often used as stimulus material to explore the cognitive and emotional characteristics of individuals with depressive disorder, while normal individuals mostly rate the scores of affective words. Given that individuals with depressive disorder exhibit a negative cognitive bias, it is possible that their depressive state could influence the ratings of affective words. To enhance the validity of the stimulus material, we specifically recruited patients with depression to provide these ratings.

Methods

This study provided subjective ratings for 501 Chinese affective norms, incorporating 167 negative words selected from depressive disorder patients’ Sino Weibo blogs, and 167 neutral words and 167 positive words selected from the Chinese Affective Word System. The norms are based on the assessments made by 91 patients with depressive disorder and 92 normal individuals, by using the paper-and-pencil quiz on a 9-point scale.

Results

Regardless of the group, the results show high reliability and validity. We identified group differences in three dimensions: valence, arousal, and self-relevance: the depression group rated negative words higher, but positive and neutral words lower than the normal control group.

Conclusion

The emotional perception affected the individual’s perception of words, to some extent, this database expanded the ratings and provided a reference for exploring norms for individuals with different emotional states.
Global, regional and national burdens of reproduction-related congenital birth defects, 1990–2019
Authors: Shen Lin , Li Jie , Zhang Hanwang , Zhao Yiqing
Published: February 2024

Background

Reproduction-related congenital birth defects (RCBDs), including Klinefelter syndrome (KS), Turner syndrome (TS), and urogenital congenital anomalies (UCA), can lead to severe physical and psychosocial disorders. The global impact of RCBDs on children and adults is unknown, which limits high-quality development of populations and increases in life expectancy per capita.

Methods

Annual incidence rates, prevalence rates (PR), and disability-adjusted life year (DALY) rates were collected for KS, TS, and UCA for 204 countries and territories, including at birth, for children younger than 1 year, and age-standardized (AS) for all ages. Linear regression was used to calculate their estimated annual percentage changes (EAPCs). Finally, the relationships between EAPCs of each indicator and sociodemographic index (SDI) was investigated using Pearson correlation analysis.

Results

Globally, the age-standardized prevalence rate (ASPR) trend is decreasing in KS and TS and increasing in UCA. The DALY rates for children younger than 1 year were on a downward trend in KS and UCA, while they were still rising for TS. The AS-DALY rates were all on a downward trend in KS, TS, and UCA. The DALY rates of KS, TS and UCA were found higher in high-income countries in North America. In addition, the burdens of TS and UCA went down with increasing SDI, whereas the burden of KS increased with increasing SDI.

Conclusion

The global burdens of RCBDs have decreased since 1990. This finding can help policymakers implement cost-effective interventions to reduce the burdens of RCBDs.
OralImmunoAnalyser: a software tool for immunohistochemical assessment of oral leukoplakia using image segmentation and classification models
Authors: Al-Tarawneh Zakaria A. , Pena-Cristóbal Maite , Cernadas Eva , Suarez-Peñaranda José Manuel , Fernández-Delgado Manuel , Mbaidin Almoutaz , Gallas-Torreira Mercedes , Gándara-Vila Pilar
Published: February 2024

Oral cancer ranks sixteenth amongst types of cancer by number of deaths. Many oral cancers are developed from potentially malignant disorders such as oral leukoplakia, whose most frequent predictor is the presence of epithelial dysplasia. Immunohistochemical staining using cell proliferation biomarkers such as ki67 is a complementary technique to improve the diagnosis and prognosis of oral leukoplakia. The cell counting of these images was traditionally done manually, which is time-consuming and not very reproducible due to intra- and inter-observer variability. The software presently available is not suitable for this task. This article presents the OralImmunoAnalyser software (registered by the University of Santiago de Compostela–USC), which combines automatic image processing with a friendly graphical user interface that allows investigators to oversee and easily correct the automatically recognized cells before quantification. OralImmunoAnalyser is able to count the number of cells in three staining levels and each epithelial layer. Operating in the daily work of the Odontology Faculty, it registered a sensitivity of 64.4% and specificity of 93% for automatic cell detection, with an accuracy of 79.8% for cell classification. Although expert supervision is needed before quantification, OIA reduces the expert analysis time by 56.5% compared to manual counting, avoiding mistakes because the user can check the cells counted. Hence, the SUS questionnaire reported a mean score of 80.9, which means that the system was perceived from good to excellent. OralImmunoAnalyser is accurate, trustworthy, and easy to use in daily practice in biomedical labs. The software, for Windows and Linux, with the images used in this study, can be downloaded from https://citius.usc.es/transferencia/software/oralimmunoanalyser for research purposes upon acceptance.
Utilization of the Intimacy and Sexuality Expression Preference tool in long-term care: a case study
Authors: Jones Cindy , Moyle Wendy , Van Haitsma Kimberly , Hudson Carly
Published: February 2024

Introduction

Sexual wellness plays a crucial role in an individual's quality of life, interpersonal relationships, and self-concept, particularly among older adults residing in residential aged care facilities, including those with dementia. However, there is currently a limited person-centered approach to understanding the unique preferences of each older person regarding their intimate and sexual behaviors. To address this gap, the Intimacy and Sexuality Expression Preference (ISEP) tool was developed to facilitate meaningful discussions between healthcare professionals or workers and older individuals about their intimacy and sexuality needs and preferences. This paper explores the use of the ISEP tool with residents in long-term aged care, including those with dementia via a user-centric case study.

Methods

ISEP tool interviews were conducted with 14 residents in a single residential aged care facility in Queensland, Australia.

Results

The study presented valuable insights and contextual information from using the ISEP tool, including an example of a resident's response, which provided recommendations for better supporting the resident. This involves engaging in supportive conversations to facilitate the exploration, implementation, and assessment of practical and actionable strategies to meet intimacy and sexuality needs and preferences.

Discussion

The ISEP tool shows promise in improving care practices and addressing the intimacy and sexuality needs of older individuals in aged care facilities. However, it is important to acknowledge that the study was conducted in a single aged care facility with a small group of residents, potentially limiting the generalisability of the findings. Further large-scale studies are necessary to establish the tool's broader applicability across different care settings.
South African adolescents' lived experiences of acquired hearing loss following multidrug-resistant tuberculosis treatment
Authors: Sparg Tarryn , Petersen Lucretia , Mayers Pat , Rogers Christine
Published: February 2024

Objective

The impact of acquiring hearing loss might be exacerbated during adolescence, as this normal transition from childhood to adulthood is characterised by identity construction and social intensity. This study aimed to describe the lived experiences of South African adolescents with acquired hearing loss following aminoglycoside treatment for multidrug resistant tuberculosis.

Design

The study adopted a descriptive phenomenological design and in-depth, semi-structured interviews were conducted in English, isiZulu and Afrikaans. The data was managed and analysed according to a modified version of Hycner's framework.

Study sample

Six participants aged 16–24 years with bilateral, mild to profound hearing loss acquired from aminoglycoside treatment were recruited from two South African provinces.

Results

Three themes emerged which created a triple burden for participants. They endured socio-economic hardship encompassing limited economic and emotional support. Participants battled the consequences of life-threatening MDR-TB including illness, hospitalisation, stigma, and other challenges. Finally, participants were left with life-changing hearing loss.

Conclusion

The findings indicate the necessity of holistic management of adolescents with aminoglycoside-related acquired hearing loss and serves as motivation to improve ototoxic monitoring practices and patient uptake of monitoring services and calls for the cessation, or at least cautious use, of aminoglycosides.
Time-dependant Bayesian knowledge tracing—Robots that model user skills over time
Authors: Salomons Nicole , Scassellati Brian
Published: February 2024

Creating an accurate model of a user’s skills is an essential task for Intelligent Tutoring Systems (ITS) and robotic tutoring systems. This allows the system to provide personalized help based on the user’s knowledge state. Most user skill modeling systems have focused on simpler tasks such as arithmetic or multiple-choice questions, where the user’s model is only updated upon task completion. These tasks have a single correct answer and they generate an unambiguous observation of the user’s answer. This is not the case for more complex tasks such as programming or engineering tasks, where the user completing the task creates a succession of noisy user observations as they work on different parts of the task. We create an algorithm called Time-Dependant Bayesian Knowledge Tracing (TD-BKT) that tracks users’ skills throughout these more complex tasks. We show in simulation that it has a more accurate model of the user’s skills and, therefore, can select better teaching actions than previous algorithms. Lastly, we show that a robot can use TD-BKT to model a user and teach electronic circuit tasks to participants during a user study. Our results show that participants significantly improved their skills when modeled using TD-BKT.
KovaaK's aim trainer as a reliable metrics platform for assessing shooting proficiency in esports players: a pilot study
Authors: Rogers Ethan J. , Trotter Michael G. , Johnson Daniel , Desbrow Ben , King Neil
Published: February 2024

Esports research lacks game-based metrics platforms appropriate for adequately capturing esports performance. The aim of this pilot study was to assess the reliability of the KovaaK's first-person shooter (FPS) aim trainer as a metrics platform for assessing shooting proficiency in esports players. Ten FPS esports players completed two identical experimental trials (T) separated by three to five days. Each trial included four rounds (R) of testing, evaluating four shooting tasks: Micro Flicking, Macro Flicking, Strafe Tracking, and Wall Peeking. Reliability of performance outcomes (e.g., accuracy, headshot accuracy, hits per second, and total shots hit) were assessed using the intraclass correlation coefficient (ICC) and their 95% confidence intervals (CI), and significant differences were identified using repeated-measures analysis of variance (RM-ANOVA). Results indicated excellent, or good to excellent reliability for all outcome variables with the ICC estimates ranging between 0.947–0.995, with lower and upper bound 95% CIs ranging between 0.876–0.988, and 0.984–0.999, respectively. Significant improvements were seen between experimental trials in the Macro Flicking task for accuracy (p = .005) and hits per second (p = .009) only. Significant interactions between trial and round were identified in the Micro Flicking task for accuracy (p = .006), with post hoc analysis showing accuracy was significantly higher in T1R1 compared to T2R1 (87.74 ± 3.13 vs. 85.99 ± 3.05, respectively, p = .02), and in T2R4 compared to T2R2 (87.99 ± 2.89 vs. 84.70 ± 4.25, respectively, p = .049). Significant interactions were also identified in the Strafe Tracking task for headshot accuracy (p = .002), with post hoc analysis showing headshot accuracy was significantly higher in T1R2 compared to T2R2 (78.48 ± 8.15 vs. 76.79 ± 12.16, respectively, p = .003), and in T1R2 compared to T1R1 (78.48 ± 8.15 vs. 73.68 ± 17.94, respectively, p = .023). In summary, this study demonstrates that KovaaK's provides a reliable metrics platform for assessing shooting proficiency in esports, however, some variability in performance was observed.
Ensembling Supervised and Unsupervised Machine Learning Algorithms for Detecting Distributed Denial of Service Attacks
Authors: Das Saikat , Ashrafuzzaman Mohammad , Sheldon Frederick T. , Shiva Sajjan
Published: February 2024

The distributed denial of service (DDoS) attack is one of the most pernicious threats in cyberspace. Catastrophic failures over the past two decades have resulted in catastrophic and costly disruption of services across all sectors and critical infrastructure. Machine-learning-based approaches have shown promise in developing intrusion detection systems (IDSs) for detecting cyber-attacks, such as DDoS. Herein, we present a solution to detect DDoS attacks through an ensemble-based machine learning approach that combines supervised and unsupervised machine learning ensemble frameworks. This combination produces higher performance in detecting known DDoS attacks using supervised ensemble and for zero-day DDoS attacks using an unsupervised ensemble. The unsupervised ensemble, which employs novelty and outlier detection, is effective in identifying prior unseen attacks. The ensemble framework is tested using three well-known benchmark datasets, NSL-KDD, UNSW-NB15, and CICIDS2017. The results show that ensemble classifiers significantly outperform single-classifier-based approaches. Our model with combined supervised and unsupervised ensemble models correctly detects up to 99.1% of the DDoS attacks, with a negligible rate of false alarms.