bluuebunny/crossref_metadata_2025 huggingface dataset:
From taboo to treatment: The emergence of psychedelics in the management of pain and opioid use disorder
Authors: Weleff Jeremy , Nunes Julio C. , Costa Gabriel P. A. , Sofuoglu Mehmet , MacLean R. Ross , De Aquino Joao P.
Published: April 2024

The rise of psychedelics in contemporary medicine has sparked interest in their potential therapeutic applications. While traditionally associated with countercultural movements and recreational use, recent research has shed light on the potential benefits of psychedelics in various mental health conditions. In this review, we explore the possible role of psychedelics in the management of chronic pain and opioid use disorder (OUD), 2 critical areas in need of innovative treatment options. Pain control remains a significant clinical challenge, particularly for individuals with OUD and those who receive long‐term opioid therapy who develop marked tolerance to opioid‐induced analgesia. Despite the magnitude of this problem, there is a scarcity of controlled studies investigating pain management alternatives for these populations. Drawing from preclinical and human evidence, we highlight the potential of psychedelics to act on shared neurobiological substrates of chronic pain and OUD, potentially reversing pain‐ and opioid‐induced neuroadaptations, such as central sensitization. We elaborate on the multifaceted dimensions of the pain experience (sensory, affective and cognitive) and their intersections that overlap with opioid‐related phenomena (opioid craving and withdrawal), hypothesizing how these processes can be modulated by psychedelics. After summarizing the available clinical research, we propose mechanistic insights and methodological considerations for the design of future translational studies and clinical trials, building on a shared clinical and neurobiological understanding of chronic pain and OUD. Our intention is to provide timely perspectives that accelerate the development and exploration of novel therapeutics for chronic pain and OUD amidst the escalating opioid crisis.
Meta‐analysis of the effect of 360‐degree videos on students' learning outcomes and non‐cognitive outcomes
Authors: Jiang Zhujun , Zhang Yicong , Chiang Feng‐Kuang
Published: April 2024

A 360‐degree video offers a novel visual experience for education. This immersive experience not only amplifies students' engagement and curiosity but also assists them in delving into and comprehending intricate concepts from a multitude of viewpoints. Given its novelty, there is a relative shortage of studies on 360‐degree video's overall effectiveness in education. This study conducted a meta‐analysis of 49 peer‐reviewed articles. Utilizing a random‐effects model to compute effect sizes (ES), the results showed that 360‐degree videos have a moderate impact on both learning (Hedges' g = 0.525) and non‐cognitive outcomes (Hedges' g = 0.527), with notable heterogeneity observed across the studies. Furthermore, the studies were coded to examine the moderating effects of their characteristics, such as the level of education, the field of education, the display types, experimental design, the sample size and the control treatment. The findings suggest a medium effect of 360‐degree videos on knowledge acquisition and a smaller effect on task performance. In terms of non‐cognitive outcomes, the least impact was noted in the domain of social and emotional qualities, while the most significant impact was in attitudes and beliefs. Based on these findings, the study proposed future research directions focusing on enhancing teaching strategies and improving research designs concerning the use of 360‐degree videos in educational contexts.

Practitioner notes

What is already known about this topic

360‐degree videos in education are notable for their authenticity, flexibility and accessibility.

They enhance learners' sense of presence, deepen understanding of subject matter and improve non‐cognitive skills.

360‐degree videos have produced mixed results on learning and non‐cognitive outcomes.

What this paper adds

360‐degree videos have a medium effect on students' learning outcomes (g = 0.0.525) and non‐cognitive outcomes (g = 0.0.527).

Significant heterogeneity is observed in the effects of 360‐degree videos on both learning outcomes and non‐cognitive outcomes.

In terms of non‐cognitive outcomes, 360‐degree videos have the smallest effect size in the social and emotional qualities domain.

Identifying key moderators that influence the effectiveness of 360‐degree videos, including participants' education levels, field of application, sample sizes, display types, experimental designs and control treatment.

Implications for practice and/or policy

Enhance social and emotional learning with 360‐degree video, and aid in understanding and managing emotional experiences.

Develop learning strategies that align with the unique characteristics of different subjects.

Teacher‐assisted approaches are encouraged to support learning and teaching in formal educational settings with structured courses.

Multimodal data can be collected for analysis in future research to explore the learning process.
Optical coherence tomography assessment of disease activity in cryopyrin‐associated periodic syndrome
Authors: Mulazzani E. , Böhm L. , Christmann T. , Krumbholz M. , Kümpfel T. , Havla J.
Published: April 2024

Background and purpose

Cryopyrin‐associated periodic syndrome is a rare autoinflammatory disease caused by gain‐of‐function mutations or variants in the NLRP3 gene. Clinically, patients suffer from a broad spectrum of both systemic and neurological symptoms. The aim of this study was to determine whether systemic inflammation demonstrated by serum amyloid A (SAA) elevation is associated with neuroinflammation assessed by optical coherence tomography (OCT).

Methods

Thirty eyes of 15 patients with NLRP3 low penetrance mutations (PwNLRP3) and 20 eyes of 10 age‐ and sex‐matched healthy controls were examined by spectral‐domain OCT as part of routine clinical care. All retinal layers and clinical features were evaluated.

Results

At baseline no significant retinal neuroaxonal inflammation or degeneration was observed in all measured retinal layers amongst PwNLRP3 compared with healthy controls. In a pooled analysis of all individual OCT time points a significant difference regarding the macular retinal nerve fibre layer was detected. Increased levels of SAA showed a positive association with averaged combined outer plexiform layer and outer nuclear layer volumes (ρ < 0.0001, r2 = 0.35).

Conclusion

In cryopyrin‐associated periodic syndrome increased combined outer plexiform layer and outer nuclear layer volumes are mirrored by SAA increase, an acute phase reactant indicating systemic inflammation. Our findings identify OCT as a candidate biomarker to monitor subclinical neuroinflammation and to assess disease activity in PwNLRP3.
TYK2 inhibition with deucravacitinib ameliorates erosive oral lichen planus
Authors: Stolte Kim Natalie , Mesas‐Fernández Alberto , Meier Katharina , Klein Edis Kaan , Dommisch Henrik , Ghoreschi Kamran , Solimani Farzan
Published: April 2024

Erosive oral lichen planus (OLP) is a challenging disease. This T cell driven disorder frequently shows a treatment unresponsive course and strongly limits patients' quality of life. The disease lacks FDA or EMA approved drugs for its treatment and the efficacy of the commonly administered treatments (i.e. topical and systemic steroids, steroid sparing agents) is often only partial. Although the etiopathogenesis of the disease still needs to be fully elucidated, recent advances helped to identify interferon‐ɣ (IFN‐ɣ) as a pivotal cytokine in OLP pathogenesis, thus making the interference with its signalling a therapeutic target. Janus kinase (JAK) inhibitors therefore gained relevance for their inhibitory effect on IFN‐ɣ signalling. While some drugs such as abrocitinib, upadacitinib, tofacitinib directly interfere with IFN‐ɣ signalling through blockade of JAK1 and/or JAK2, deucravacitinib, a selective TYK‐2 inhibitor indirectly interferes on IFN‐ɣ activation through interference with interleukin (IL)‐12, a potent promotor for Th1/IFN‐ɣ responses. This mechanism of action makes deucravacitinib a candidate drug for the treatment of OLP. Here we provide initial evidence that deucravacitinib 6 mg daily has a beneficial effect in three patients with oral OLP.
RETRACTED: Meta‐analysis comparing different ultrasound detection methods to accurately assess wound healing and scar formation after caesarean section
Authors: Miao Jing‐Jing , Luo Ying‐Ying , Wang Chen‐Yu , Li Hui‐Xia , Yu Hong‐Xia
Published: April 2024

The accurate assessment of wound healing post‐caesarean section, especially in twin pregnancies, remains a pivotal concern in obstetrics, given its implications for maternal health and recovery. Traditional methods, including conventional abdominal ultrasonography (CU), have been challenged by the advent of transvaginal ultrasonography (TU), offering potentially enhanced sensitivity and specificity. This meta‐analysis directly compares the efficacy of TU and CU in evaluating wound healing and scar formation, crucial for optimizing postoperative care. Results indicate that TU is associated with significantly better outcomes in wound healing, demonstrated by lower REEDA scores (SMD = −20.56, 95% CI: [−27.34.20, −13.77], p < 0.01), and in scar formation reduction, evidenced by lower Manchester Scar Scale scores (SMD = −25.18, 95% CI: [−29.98, −20.39], p < 0.01). These findings underscore the potential of integrating TU into routine post‐caesarean evaluation protocols to enhance care quality and patient recovery.
Contraction and expansion: global geographical variation in reproductive systems of Primula is driven by different mechanisms
Authors: Shi Honghua , Yang Bin , Lyu Tong , Wang Zhiheng , Sun Hang
Published: April 2024

Aim

Reproductive systems strongly influence plants' evolution and adaption, and the biogeographic pattern of its variation has intrigued biologists and ecologists. Here, to test the impacts of paleoglaciation on plants' reproductive system variation, we compared the geographical pattern and environmental drivers in the proportions of different reproductive systems in Primula in regions affected and unaffected by paleoglaciation.

Location

Global.

Time Period

Since the Last Glacial Maximum (LGM).

Major Taxa Studied

Primula.

Methods

Using data on reproductive systems and distributions of 604 Primula taxa around the world and 221 along the elevational gradient of the Himalayas, we demonstrated the global pattern and the elevational pattern in the proportions of homostylous taxa. We employed general linear models to establish the relationship between the proportion of homostylous taxa and environmental variables and hierarchical partitioning to assess the relative contributions of these variables in both regions affected and unaffected by paleoglaciation, respectively.

Results

We found a higher proportion of homostylous taxa in regions glaciated during the LGM than those unglaciated, with different latitudinal patterns and climate drivers. The proportion of homostylous taxa showed varying trends across different regions: increasing with latitude and temperature anomaly in glaciated regions while concentrating at lower latitudes with higher winter temperatures in unglaciated regions. Additionally, homostylous taxa were more prevalent at lower elevations in the Himalayas.

Main Conclusions

Our study provides the first quantitative evidence for the hypothesis that selfers are more prevailing in regions affected by paleoglaciation facilitated by recolonization via comparing the geographic pattern and drivers in regions affected and unaffected by paleoglaciation. Our findings also reveal the concentrated distribution of homostylous taxa in Primula at low latitudes, which may be the result of population shrinkage caused by heat stress, facing a more severe survival crisis under the circumstances of global warming and increasing human activities.
Predictable time‐series biases in analyst target prices and stock returns
Authors: Vafaeimehr Ahmadreza
Published: April 2024

Target prices often draw criticism because of their optimistic nature and lack of substantial investment value. I provide evidence that removing predictable time‐series biases in target prices significantly improves the information content of these estimates. Empirical tests do not support that these benefits stem from market underreaction to predictable biases. Instead, evidence indicates the informativeness of unbiased estimates about priced risk factors beyond common factors. Unbiasing target prices may improve their ability to capture time‐series momentum. Finally, I delve into the methodological facets of the unbiasing procedure, leading to the development of frameworks that possess tangible practical relevance.
Risk stratification of synchronous gastric cancers including alcohol‐related genetic polymorphisms
Authors: Asonuma Sho , Hatta Waku , Koike Tomoyuki , Okata Hideki , Uno Kaname , Iwai Wataru , Saito Masashi , Yonechi Makoto , Fukushi Daisuke , Kayaba Shoichi , Kikuchi Ryosuke , Ito Hirotaka , Fushiya Jun , Maejima Ryuhei , Abe Yasuhiko , Kawamura Masashi , Honda Junya , Kondo Yutaka , Dairaku Naohiro , Toda Shusuke , Watanabe Kenta , Takahashi Kiichi , Echigo Hiroharu , Abe Yasuaki , Endo Hiroyuki , Okata Tomoki , Hoshi Tatsuya , Kinoshita Kenji , Kisoi Madoka , Nakamura Tomohiro , Nakaya Naoki , Iijima Katsunori , Masamune Atsushi
Published: April 2024

Background and Aim

We previously identified that ever‐smoking and severe gastric atrophy in pepsinogen are risk factors for synchronous gastric cancers (SGCs). This study aimed to determine the association of alcohol drinking status or alcohol‐related genetic polymorphism with SGCs and also stratify their risk.

Methods

This multi‐center prospective cohort study included patients who underwent endoscopic submucosal dissection for the initial early gastric cancers at 22 institutions in Japan. We evaluated the association of alcohol drinking status or alcohol dehydrogenase 1B (ADH1B) and acetaldehyde dehydrogenase 2 (ALDH2) genotypes with SGCs. We then stratified the risk of SGCs by combining prespecified two factors and risk factors identified in this study.

Results

Among 802 patients, 130 had SGCs. Both the ADH1B Arg and ALDH2 Lys alleles demonstrated a significant association with SGCs on multivariate analysis (odds ratio, 1.77), although alcohol drinking status showed no association. The rates of SGCs in 0–3 risk factors in the combined evaluation of three risk factors (ever‐smoking, severe gastric atrophy in pepsinogen, and both the ADH1B Arg and ALDH2 Lys alleles) were 7.6%, 15.0%, 22.0%, and 32.1%, respectively. The risk significantly increased from 0 to 3 risk factors on multivariate analysis (P for trend <0.001).

Conclusions

Both the ADH1B Arg and ALDH2 Lys alleles were at high risk for SGCs. The risk stratification by these three factors may be a less invasive and promising tool for predicting their risk.
Mitigation of retinol‐induced skin irritation by physiologic lipids: Evidence from patch testing
Authors: Fang Ye , Ying Ye , Xiaolan Wei , Lin Sun , Chenlan Xu , Caixia Wang , Dingqiao Lin , Yanan Li
Published: April 2024

Background

There is a dearth of effective treatments to counter retinol‐induced skin irritation.

Objective

This study aimed to investigate the efficacy of three potential mitigants: (i) phytosteryl/octyldodecyl lauroyl glutamate (PLG), (ii) a physiologic lipid mixture (PLM) comprised of ceramide three and cholesterol, and (iii) niacinamide, in ameliorating irritation instigated by retinol.

Methods

An occlusive human patch test, spanning 5 days, was undertaken on 18 Chinese participants aged between 23 and 40. It was designed as a randomized, double‐blind, and vehicle‐controlled study. Clinician erythema assessment (CEA) and instrumental evaluations were employed pre and post‐test. Subsequently, a 4‐week consumer in‐use test, randomized and double‐blind in nature, was executed to substantiate the soothing effects of PLG.

Results

Data from CEA and bioengineering assessments revealed that, in comparison to the vehicle control, both 2% PLG and 5% PLM notably curbed retinol‐induced skin erythema and inflammation. Notably, PLG outperformed PLM. Conversely, 3% niacinamide did not offer relief against retinol‐induced discomfort. The subsequent consumer in‐use test affirmed that treatments with 2% PLG were better tolerated than those with the vehicle alone.

Conclusion

To the best of our knowledge, this study represents the first confirmation that physiologic lipids effectively mitigate retinol‐induced irritation. Given their capacity to counter retinol‐induced irritation, physiologic lipids, particularly PLG, are recommended for incorporation in retinol regimens. Additionally, the Visia‐CR a* value can serve as a robust objective measure for interpreting patch test outcomes.
Low‐temperature thermal and physical properties of lunar meteorites
Authors: Macke R. J. , Opeil C. P. , Britt D. T. , Consolmagno G. J. , Irving A.
Published: April 2024

Lunar meteorites are the most diverse and readily available specimens for the direct laboratory study of lunar surface materials. In addition to informing us about the composition and heterogeneity of lunar material, measurements of their thermo‐physical properties provide data necessary to inform the models of the thermal evolution of the lunar surface and provide data on fundamental physical properties of the surface material for the design of exploration and resource extraction hardware. Low‐temperature data are particularly important for the exploration of low‐temperature environments of the lunar poles and permanently shadowed regions. We report low‐temperature‐specific heat capacity, thermal conductivity, and linear thermal expansion for six lunar meteorites: Northwest Africa [NWA] 5000, NWA 6950, NWA 8687, NWA 10678, NWA 11421, and NWA 11474, over the range 5 ≤ T ≤ 300 K. From these, we calculate thermal inertia and thermal diffusivity as functions of temperature. Additionally, heat capacities were measured for 15 other lunar meteorites, from which we calculate their Debye temperature and effective molar mass.
Well‐being and dignity in innovative digitally‐led healthcare for aged adults
Authors: Raja Moonika , Uhrenfeldt Lisbeth
Published: April 2024

Dignity is a central value in care for aged adults, and it must be protected and respected. With demographic changes leading to an aging population, health ministries are increasingly investing in digitalization. However, using unfamiliar digital technology can be challenging and thus impact aged adults' dignity and well‐being. The INNOVATEDIGNITY project aims to research new, dignified ways of engaging with aged adults to shape digital developments in care delivery. This qualitative study aimed to explore how innovative digitally‐led healthcare have influenced aged adults' well‐being and dignity through three studies conducted as part of the INNOVATEDIGNITY project: a scoping review, an empirical study and a policy analysis. The three documents were analysed to uncover meanings relevant to the research problem revealing four main themes: the advantages of new technologies in facilitating aged adults' well‐being, the rupture of dignity due to bewilderment in the digital world, aged adults' dignity is affected by their worries about human face of care being replaced by technology and preserving aged adults' dignity in digitally‐led healthcare. Digitalization in healthcare impacts aged adults' well‐being as providing new opportunities for care, but preserving aged adults' dignity when working with unfamiliar digital innovations is challenging. Aged adults need to be informed about the use of technology in their care and supported to develop the necessary digital skills to better adapt to digitally‐led healthcare. The circumstances, conditions and needs of individuals should remain central when implementing new technologies in healthcare settings in a dignified way.
Long‐term outcome of pediatric renal transplantation with donors younger than 6 years
Authors: Ramirez‐Amoros Carla , San Basilio Maria , Amesty Virginia , Rivas Susana , Lobato Roberto , Fernandez‐Camblor Carlota , Lopez‐Pereira Pedro , Martinez‐Urrutia Maria Jose
Published: April 2024

Background

Renal transplantation is currently the best treatment option for patients with end‐stage renal disease. However, the use of kidneys from donors under 6 years of age as a possibility to increase the organ pool in pediatric recipients remains a controversial matter. We aimed to investigate whether donor age is associated to the long‐term functionality of the renal graft. Likewise, we analyzed the adaptation of the graft to the ascending functional requirements in the pediatric patient.

Methods

Retrospective study of the results obtained in pediatric recipients transplanted with grafts from donors between 3 and 6 years of age, comparing them with those of grafts from donors older than 6 years. Among the variables compared are cumulative graft survival, renal size, need for antiproteinuric therapy, GFR, incidence of rejection, pyelonephritis, renal failure and surgical or tumor complications.

Results

A total of 43 transplants were performed with donors aged 3–6 years, and 42 transplants with donors older than 6 years. Cumulative graft survival at 5 years was 81% for the younger donor group compared to 98% for the older donor group (p < .05). At 8 years, cumulative graft survival for donors <6 years was 74%. As for the mean estimated graft survival, it was 11.52 years for the younger donor group and 14.51 years for older donors. During follow‐up, the younger donor group presented greater renal enlargement and need for antiproteinuric therapy. The older donors group had a higher GFR during the first year of follow‐up, which then equalized in both groups. There were no statistically significant differences in the incidence of acute or chronic rejection, acute pyelonephritis, acute renal failure or surgical or tumor complications.

Conclusions

Renal transplants of grafts equal to or less than 6 years old have good short‐term and acceptable long‐term results in pediatric patients.
Schopenhauer on the inconsistency between optimism and personal immortality
Authors: Segev Mor
Published: April 2024

For Schopenhauer, death, understood as the annihilation of an individual's existence, cannot be successfully accommodated by theories endorsing an optimistic assessment of both human life and the world at large. I argue that Schopenhauer also has reasons to think that optimism cannot adopt personal immortality as a solution to that problem, although he does not present them systematically. Thus, he argues, prolonging one's life would necessarily lead at some point to an unbearable state of exhaustion due to one's unchanging character. Changing one's character infinitely many times in the future would not do either, as Schopenhauer regards that idea as internally inconsistent. Finally, the immortality gained through one's work, one's descendants, or the survival of a part of oneself, while consistent with optimism, could not amount to personal immortality, on Schopenhauer's criteria. I end by discussing the implications of Schopenhauer's criticism for his own view, and a possible reply to it.
Individual and day‐to‐day differences in domain‐specific physical activity of 10‐ to 11‐year‐old children in Denmark—Measured using GPS and accelerometry
Authors: Stage Anna , Amholt Thea Toft , Schipperijn Jasper
Published: April 2024

Objective

Physical activity (PA) and the achievement of 60 min of moderate‐to‐physical‐activity daily is declining in school‐aged‐children, and effective strategies to increase PA is needed. We aimed to examine the individual and day‐to‐day distribution of PA on schooldays among children aged 10–11 in 4 domains—school, home, transport, and other.

Methods

Data were collected from August to September 2020 using accelerometer and GPS data to measure daily PA‐levels and to locate in which domain PA occurs. Daily PA‐levels were assessed in each domain, and analyses of the individual and day‐to‐day differences in PA‐levels were calculated.

Results

The school domain contributed the most to children's daily MVPA with 47% of average MVPA, followed by the home domain with 26% of daily average MVPA, the other domain with 19% of daily average MVPA and the transport domain with 8% of daily average MVPA. Our results showed individual differences in where PA occurs, day‐to‐day differences in total MVPA and day‐to‐day differences in the MVPA‐levels across domains.

Conclusions

The school domain contributed the most to children's MVPA‐levels followed by the domains of home, other, and transport. Our study indicated that PA‐levels and the distribution of PA across domains differ from day‐to‐day. Future interventions should target more than one domain to accommodate these individual‐ and day‐to‐day differences in the goal of increasing PA‐levels and to reduce the decline in PA seen from childhood to adolescence.
Aggregates in apheresis‐derived platelet concentrates: A 5‐year single‐centre experience
Authors: Vinković Matea , Hećimović Ana , Jukić Irena , Vuk Tomislav
Published: April 2024

Background and Objectives

The phenomenon of aggregates in apheresis‐derived platelet concentrates (APCs) has not yet been fully elucidated. Initially, visible aggregates (IVA) usually dissolve within 24 h after collection, but some persist till the end of the shelf life (persistent aggregates, PA). A study conducted at the Croatian Institute of Transfusion Medicine aimed to identify factors that influence the aggregate occurrence in APCs.

Materials and Methods

We conducted a cross‐sectional study for the 2018–2022 period and collected data on APCs with IVA. We analysed APCs discarded due to PA separately for two apheresis technologies and compared them to the control group.

Results

Significantly more donations were discarded in the IVA group compared with the control group and total number of discarded APCs. A total of 205 APCs were discarded due to PA (14.7% of IVA APCs and 1.27% of all APCs collected). Amicus APCs with PA had a significantly lower platelet count and mean platelet volume. They were obtained by procedures with less anticoagulant used. In contrast to Amicus APCs, Haemonetics APCs with PA had a significantly higher platelet count. None of the donor‐related factors examined was predictive of PA.

Conclusion

APCs with IVA are more often discarded, not only due to aggregates, but also for impairment of other quality control parameters. Type of apheresis technology, being one of the most common risk factors for IVA, was not confirmed as the main risk factor for PA. There seem to be some donor‐related causal factors.
The development of Maltese English
Authors: Grech Sarah
Published: April 2024

There has been a more or less constant presence of the English language in the Maltese islands since British settlement began to establish itself during the 1800s. The necessity of accommodating foreign rulers or visitors fuelled a well‐established linguistic dexterity in the islanders, who are documented to have used what came to be designated as Maltese amongst themselves, alongside any other languages necessary with anyone else. Today, fluency in at least Maltese and English remains the preferred linguistic scenario, and both are generally considered necessary to be able to get involved in Maltese society.
Coxiella burnetii serostatus in dromedary camels (Camelus dromedarius) is associated with the presence of C. burnetii DNA in attached ticks in Laikipia County, Kenya
Authors: Rooney Tess , Fèvre Eric M. , Villinger Jandouwe , Brenn‐White Maris , Cummings Charles O. , Chai Daniel , Kamau Joseph , Kiyong'a Alice , Getange Dennis , Ochieng Dickens O. , Kivali Velma , Zimmerman Dawn , Rosenbaum Marieke , Nutter Felicia B. , Deem Sharon L.
Published: April 2024

Aims

Q fever is a globally distributed, neglected zoonotic disease of conservation and public health importance, caused by the bacterium Coxiella burnetii. Coxiella burnetii normally causes subclinical infections in livestock, but may also cause reproductive pathology and spontaneous abortions in artiodactyl species. One such artiodactyl, the dromedary camel (Camelus dromedarius), is an increasingly important livestock species in semi‐arid landscapes. Ticks are naturally infected with C. burnetii worldwide and are frequently found on camels in Kenya. In this study, we assessed the relationship between dromedary camels' C. burnetii serostatus and whether the camels were carrying C. burnetii PCR‐positive ticks in Kenya. We hypothesized that there would be a positive association between camel seropositivity and carrying C. burnetii PCR‐positive ticks.

Methods and Results

Blood was collected from camels (N = 233) from three herds, and serum was analysed using commercial ELISA antibody test kits. Ticks were collected (N = 4354), divided into pools of the same species from the same camel (N = 397) and tested for C. burnetii and Coxiella‐like endosymbionts. Descriptive statistics were used to summarize seroprevalence by camel demographic and clinical variables. Univariate logistic regression analyses were used to assess relationships between serostatus (outcome) and tick PCR status, camel demographic variables, and camel clinical variables (predictors). Camel C. burnetii seroprevalence was 52%. Across tick pools, the prevalence of C. burnetii was 15% and Coxiella‐like endosymbionts was 27%. Camel seropositivity was significantly associated with the presence of a C. burnetii PCR‐positive tick pool (OR: 2.58; 95% CI: 1.4–5.1; p = 0.0045), increasing age class, and increasing total solids.

Conclusions

The role of ticks and camels in the epidemiology of Q fever warrants further research to better understand this zoonotic disease that has potential to cause illness and reproductive losses in humans, livestock, and wildlife.
Dynamic cerebral autoregulation is governed by two time constants: Arterial transit time and feedback time constant
Authors: Payne Stephen J.
Published: April 2024

Dynamic cerebral autoregulation (dCA) is the mechanism that describes how the brain maintains cerebral blood flow approximately constant in response to short‐term changes in arterial blood pressure. This is known to be impaired in many different pathological conditions, including ischaemic and haemorrhagic stroke, dementia and traumatic brain injury. Many different approaches have thus been used both to analyse and to quantify this mechanism in a range of healthy and diseased subjects, including data‐driven models (in both the time and the frequency domain) and biophysical models. However, despite the substantial body of work on both biophysical models and data‐driven models of dCA, there remains little work that links the two together. One of the reasons for this is proposed to be the discrepancies between the time constants that govern dCA in models and in experimental data. In this study, the processes that govern dCA are examined and it is proposed that the application of biophysical models remains limited due to a lack of understanding about the physical processes that are being modelled, partly due to the specific model formulation that has been most widely used (the equivalent electrical circuit). Based on the analysis presented here, it is proposed that the two most important time constants are arterial transit time and feedback time constant. It is therefore time to revisit equivalent electrical circuit models of dCA and to develop a more physiologically realistic alternative, one that can more easily be related to experimental data.

image

Key points

Dynamic cerebral autoregulation is governed by two time constants.

The first time constant is the arterial transit time, rather than the traditional ‘RC’ time constant widely used in previous models.

This arterial transit time is approximately 1 s in the brain.

The second time constant is the feedback time constant, which is less accurately known, although it is somewhat larger than the arterial transit time.

The equivalent electrical circuit model of dynamic cerebral autoregulation should be replaced with a more physiologically representative model.
Calcineurin regulates synaptic Ca2+‐permeable AMPA receptors in hypothalamic presympathetic neurons via α2δ‐1‐mediated GluA1/GluA2 assembly
Authors: Zhou Jing‐Jing , Shao Jian‐Ying , Chen Shao‐Rui , Chen Hong , Pan Hui‐Lin
Published: April 2024

Hypertension is a major adverse effect of calcineurin inhibitors, such as tacrolimus (FK506) and cyclosporine, used clinically as immunosuppressants. Calcineurin inhibitor‐induced hypertension (CIH) is linked to augmented sympathetic output from the hypothalamic paraventricular nucleus (PVN). GluA2‐lacking, Ca2+‐permeable AMPA receptors (CP‐AMPARs) are a key feature of glutamatergic synaptic plasticity, yet their role in CIH remains elusive. Here, we found that systemic administration of FK506 in rats significantly increased serine phosphorylation of GluA1 and GluA2 in PVN synaptosomes. Strikingly, FK506 treatment reduced GluA1/GluA2 heteromers in both synaptosomes and endoplasmic reticulum‐enriched fractions from the PVN. Blocking CP‐AMPARs with IEM‐1460 induced a larger reduction of AMPAR‐mediated excitatory postsynaptic current (AMPAR‐EPSC) amplitudes in retrogradely labelled, spinally projecting PVN neurons in FK506‐treated rats than in vehicle‐treated rats. Furthermore, FK506 treatment shifted the current–voltage relationship of AMPAR‐EPSCs from linear to inward rectification in labelled PVN neurons. FK506 treatment profoundly enhanced physical interactions of α2δ‐1 with GluA1 and GluA2 in the PVN. Inhibiting α2δ‐1 with gabapentin, α2δ‐1 genetic knockout, or disrupting α2δ‐1–AMPAR interactions with an α2δ‐1 C terminus peptide restored GluA1/GluA2 heteromers in the PVN and diminished inward rectification of AMPAR‐EPSCs in labelled PVN neurons induced by FK506 treatment. Additionally, microinjection of IEM‐1460 or α2δ‐1 C terminus peptide into the PVN reduced renal sympathetic nerve discharges and arterial blood pressure elevated in FK506‐treated rats but not in vehicle‐treated rats. Thus, calcineurin in the hypothalamus constitutively regulates AMPAR subunit composition and phenotypes by controlling GluA1/GluA2 interactions with α2δ‐1. Synaptic CP‐AMPARs in PVN presympathetic neurons contribute to augmented sympathetic outflow in CIH.

image

Key points

Systemic treatment with the calcineurin inhibitor increases serine phosphorylation of synaptic GluA1 and GluA2 in the PVN.

Calcineurin inhibition enhances the prevalence of postsynaptic Ca2+‐permeable AMPARs in PVN presympathetic neurons.

Calcineurin inhibition potentiates α2δ‐1 interactions with GluA1 and GluA2, disrupting intracellular assembly of GluA1/GluA2 heterotetramers in the PVN.

Blocking Ca2+‐permeable AMPARs or α2δ‐1–AMPAR interactions in the PVN attenuates sympathetic outflow augmented by the calcineurin inhibitor.
Two-Fluid and Discrete Element Modeling of a Parallel Plate Fluidized Bed Heat Exchanger for Concentrating Solar Power
Authors: Appaswamy Krutika , Schirck Jason , Punchi Wedikkara Chathusha , Morris Aaron , Ma Zhiwen
Published: April 2024

A novel high-temperature particle solar receiver is developed using a light trapping planar cavity configuration. As particles fall through the cavity, the concentrated solar radiation warms the boundaries of the receiver and in turn heats the particles. Particles flow through the system, forming a fluidized bed at the lower section, leaving the system from the bottom at a constant flowrate. Air is introduced to the system as the fluidizing medium to improve particle heat transfer and mixing. A laboratory scale cavity receiver is built by collaborators at the Colorado School of Mines and their data are used for model validation. In this experimental setup, near IR quartz lamp is used to provide flux to the vertical wall of the heat exchanger. The system is modeled using the discrete element method and a continuum two-fluid method. The computational model matches the experimental system size and the particle size distribution is assumed monodisperse. A new continuum conduction model that accounts for the effects of solid concentration is implemented, and the heat flux boundary condition matches the experimental setup. Radiative heat transfer is estimated using a widely used correlation during the post-processing step to determine an overall heat transfer coefficient. The model is validated against testing data and achieves less than 30% discrepancy and a heat transfer coefficient greater than 1000 W/m2 K.
A Separation Modeling Method for Morphing QUAV: Analytical Solutions for Constraint Forces Under Deformation
Authors: Dong Fangfang , Yuan Baotao , Zhao Xiaomin , Chen Ye-Hwa , Chen Shan
Published: April 2024

A morphing quadrotor unmanned aerial vehicle (QUAV) possesses the remarkable ability to alter its shape, enabling it to navigate through gaps smaller than its wingspan. However, these deformations result in changes to the system's center of gravity and moment of inertia, necessitating real-time computation of each state's variations. To address this challenge, we propose a dynamic modeling approach based on the Udwadia−Kalaba (U-K) method. The morphing QUAV is divided into three separate subsystems, with the dynamic modeling for each subsystem conducted independently. Subsequently, the QUAV's deformation states and inherent structure are introduced in the form of constraints, and the constrained forces are derived using the U-K equation. By combining these analytical solutions, the model of the QUAV under continuous deformation is obtained. This approach effectively simplifies the modeling computations caused by changes in the system's center of gravity and moment of inertia during deformation. A control approach is proposed to achieve attitude stabilization and altitude control for the morphing QUAV. Ultimately, the stable motion of the morphing QUAV is validated through numerical simulations.
Investigation of Fiber Orientation of Fused Filament Fabricated CFRP Composites via an External Magnetic Field
Authors: Zhang Haoran , Wang Kaifeng
Published: April 2024

For carbon fiber-reinforced plastic (CFRP) composites, controlling the interior fiber distribution and orientation during the manufacturing process is a common approach to optize the structural performance of fabricated parts. However, few studies have been conducted to investigate fiber alignment during the additive manufacturing of CFRP composites. This study proposes a magnetic field controlled (MFC) method to control the fiber orientation during the fused filament fabrication (FFF) of nickel-coated carbon fiber (NCF) reinforced polymer composites. Firstly, a theoretical analysis model is established to explore the suitable magnetic field intensity for fiber rotation. Secondly, a customized FFF system with MFC components is implemented, and a polylactic acid matrix composite containing 10 wt% NCF is printed to validate the feasibility of the proposed approach. The microstructure of the printed samples is examined to assess the effectiveness of the method. Finally, uniaxial tensile tests are performed to investigate the impact of fiber orientation adjustment on mechanical properties. The experimental results reveal that the MFC method can effectively align the interior fiber orientation of CFRP composites, leading to a significant increase in the tensile strength (approximately 8.8%) and Young's modulus (around 10.5%) of the printed samples.
Ultralow-power optoelectronic synaptic transistors based on polyzwitterion dielectrics for in-sensor reservoir computing
Authors: Wu Xiaosong , Shi Shuhui , Liang Baoshuai , Dong Yu , Yang Rumeng , Ji Ruiduan , Wang Zhongrui , Huang Weiguo
Published: April 2024

Bio-inspired transistor synapses use solid electrolytes to achieve low-power operation and rich synaptic behaviors via ion diffusion and trapping. While these neuromorphic devices hold great promise, they still suffer from challenges such as high leakage currents and power consumption, electrolysis risk, and irreversible conductance changes due to long-range ion migrations and permanent ion trapping. In addition, their response to light is generally limited because of “exciton-polaron quenching”, which restricts their potential in in-sensor neuromorphic visions. To address these issues, we propose replacing solid electrolytes with polyzwitterions, where the cation and anion are covalently concatenated via a flexible alkyl chain, thus preventing long-range ion migrations while inducing good photoresponses to the transistors via interfacial charge trapping. Our detailed studies reveal that polyzwitterion-based transistors exhibit optoelectronic synaptic behavior with ultralow-power consumption (~250 aJ per spike) and enable high-performance in-sensor reservoir computing, achieving 95.56% accuracy in perceiving the trajectory of moving basketballs.
Increased β
2
-adrenergic signaling promotes fracture healing through callus neovascularization in mice
Authors: Jahn Denise , Knapstein Paul Richard , Otto Ellen , Köhli Paul , Sevecke Jan , Graef Frank , Graffmann Christine , Fuchs Melanie , Jiang Shan , Rickert Mayla , Erdmann Cordula , Appelt Jessika , Revend Lawik , Küttner Quin , Witte Jason , Rahmani Adibeh , Duda Georg , Xie Weixin , Donat Antonia , Schinke Thorsten , Ivanov Andranik , Tchouto Mireille Ngokingha , Beule Dieter , Frosch Karl-Heinz , Baranowsky Anke , Tsitsilonis Serafeim , Keller Johannes
Published: April 2024

Traumatic brain injury (TBI) leads to skeletal changes, including bone loss in the unfractured skeleton, and paradoxically accelerates healing of bone fractures; however, the mechanisms remain unclear. TBI is associated with a hyperadrenergic state characterized by increased norepinephrine release. Here, we identified the β
2
-adrenergic receptor (ADRB2) as a mediator of skeletal changes in response to increased norepinephrine. In a murine model of femoral osteotomy combined with cortical impact brain injury, TBI was associated with ADRB2-dependent enhanced fracture healing compared with osteotomy alone. In the unfractured 12-week-old mouse skeleton, ADRB2 was required for TBI-induced decrease in bone formation and increased bone resorption. Adult 30-week-old mice had higher bone concentrations of norepinephrine, and ADRB2 expression was associated with decreased bone volume in the unfractured skeleton and better fracture healing in the injured skeleton. Norepinephrine stimulated expression of vascular endothelial growth factor A and calcitonin gene–related peptide-α (αCGRP) in periosteal cells through ADRB2, promoting formation of osteogenic type-H vessels in the fracture callus. Both ADRB2 and αCGRP were required for the beneficial effect of TBI on bone repair. Adult mice deficient in

ADRB2 without TBI developed fracture nonunion despite high bone formation in uninjured bone. Blocking ADRB2 with propranolol impaired fracture healing in mice, whereas the ADRB2 agonist formoterol promoted fracture healing by regulating callus neovascularization. A retrospective cohort analysis of 72 patients with long bone fractures indicated improved callus formation in 36 patients treated with intravenous norepinephrine. These findings suggest that ADRB2 is a potential therapeutic target for promoting bone healing.
Antibacterial insights into alternariol and its derivative alternariol monomethyl ether produced by a marine fungus
Authors: Li Rongmei , Su Zhenjie , Sun Chaomin , Wu Shimei
Published: April 2024

Alternaria alternata
FB1 is a marine fungus identified as a candidate for plastic degradation in our previous study. This fungus has been recently shown to produce secondary metabolites with significant antimicrobial activity against various pathogens, including methicillin-resistant
Staphylococcus aureus
(MRSA) and the notorious aquaculture pathogen
Vibrio anguillarum
. The antibacterial compounds were purified and identified as alternariol (AOH) and its derivative, alternariol monomethyl ether (AME). We found that AOH and AME primarily inhibited pathogenic bacteria (MRSA or
V. anguillarum
) by disordering cell division and some other key physiological and biochemical processes. We further demonstrated that AOH could effectively inhibit the unwinding activity of MRSA topoisomerases, which are closely related to cell division and are the potential action target of AOH. The antibacterial activities of AOH and AME were verified by using zebrafish as the
in vivo
model. Notably, AOH and AME did not significantly affect the viability of normal human liver cells at concentrations that effectively inhibited MRSA or
V. anguillarum
. Finally, we developed the genetic operation system of
A. alternata
FB1 and blocked the biosynthesis of AME by knocking out
omtI
(encoding an O-methyl transferase), which facilitated
A. alternata
FB1 to only produce AOH. The development of this system in the marine fungus will accelerate the discovery of novel natural products and further bioactivity study.

IMPORTANCE

More and more scientific reports indicate that alternariol (AOH) and its derivative alternariol monomethyl ether (AME) exhibit antibacterial activities. However, limited exploration of their detailed antibacterial mechanisms has been performed. In the present study, the antibacterial mechanisms of AOH and AME produced by the marine fungus
Alternaria alternata
FB1 were disclosed
in vitro
and
in vivo
. Given their low toxicity on the normal human liver cell line under the concentrations exhibiting significant antibacterial activity against different pathogens, AOH and AME are proposed to be good candidates for developing promising antibiotics against methicillin-resistant
Staphylococcus aureus
and
Vibrio anguillarum
. We also succeeded in blocking the biosynthesis of AME, which facilitated us to easily obtain pure AOH. Moreover, based on our previous results,
A. alternata
FB1 was shown to enable polyethylene degradation.