bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring causes and predictors of cyberbullying in gifted and non-gifted students: Academic success, psychological variables, parental and educators’ supervision, motivation, and reactions to cyber victimization
Authors: Yildiz Durak Hatice , Kıdıman Esra , Şenel Selma , Özüdoğru Gül
Published: July 2024

The purpose of this study is to explore the motivation of cyberbullying behaviors, their reactions to these behaviors, and the predictors of cyberbullying sensibility in gifted and non-gifted students. The study reached 258 participants, including 102 gifted and 156 non-gifted students. This research is a descriptive survey model. The study performed descriptive statistics, independent samples t-test, ordinal logistic regression analysis, and structural equation modeling to examine the status of the variables examined according to gifted and non-gifted students. The most important reason for cyberbullying behaviors in both gifted and non-gifted students was to take revenge, and the least important reason was to adapt. The most common reaction to cyber victimization is deleting shares or files that may cause harm. Gifted and non-gifted female students have more cyberbullying sensibility. Gifted students with a high academic average have more cyberbullying sensibility. In addition, students with gifted and non-gifted internal functional regulation of emotions skills have more cyberbullying sensibility. Students with low external dysfunctional regulation of emotions scores also have more cyberbullying sensibility. The results confirmed the importance of identifying students at risk, identifying the distinguishing factors for cyberbullying behaviors of gifted and non-gifted high school students, and evaluating the sources and reactions of cyberbullying behaviors. These results will provide important input for school-based prevention studies.
Beyond Menstrual Dysfunction: Does Altered Endocrine Function Caused by Problematic Low Energy Availability Impair Health and Sports Performance in Female Athletes?
Authors: Ihalainen Johanna K. , Mikkonen Ritva S. , Ackerman Kathryn E. , Heikura Ida A. , Mjøsund Katja , Valtonen Maarit , Hackney Anthony C.
Published: July 2024

Low energy availability, particularly when problematic (i.e., prolonged and/or severe), has numerous negative consequences for health and sports performance as characterized in relative energy deficiency in sport. These consequences may be driven by disturbances in endocrine function, although scientific evidence clearly linking endocrine dysfunction to decreased sports performance and blunted or diminished training adaptations is limited. We describe how low energy availability-induced changes in sex hormones manifest as menstrual dysfunction and accompanying hormonal dysfunction in other endocrine axes that lead to adverse health outcomes, including negative bone health, impaired metabolic activity, undesired outcomes for body composition, altered immune response, problematic cardiovascular outcomes, iron deficiency, as well as impaired endurance performance and force production, all of which ultimately may influence athlete health and performance. Where identifiable menstrual dysfunction indicates hypothalamic-pituitary-ovarian axis dysfunction, concomitant disturbances in other hormonal axes and their impact on the athlete’s health and sports performance must be recognized as well. Given that the margin between podium positions and “losing” in competitive sports can be very small, several important questions regarding low energy availability, endocrinology, and the mechanisms behind impaired training adaptations and sports performance have yet to be explored.
Sex Differences Across Concussion Characteristics in US Service Academy Cadets: A CARE Consortium Study
Authors: Kelly Louise A. , Caccese J. B. , Jain D. , Master C. L. , Lempke L. , Memmini A. K. , Buckley T. A. , Clugston J. R. , Mozel A. , Eckner J. T. , Susmarski A. , Ermer E. , Cameron K. L. , Chrisman S. , Pasquina P. , Broglio S. P. , McAllister T. W. , McCrea M. , Esopenko C. ,   CARE Consortium Investigators
Published: July 2024

Objective

To describe sex differences in concussion characteristics in US Service Academy cadets.

Design

Descriptive epidemiology study.

Setting

Four US service academies.

Participants

2209 cadets (n = 867 females, n = 1342 males).

Independent Variable

Sex.

Outcome Measures

Injury proportion ratios (IPR) compared the proportion of injuries by sex (females referent) for injury situation, certainty of diagnosis, prolonged recovery, recurrent injuries, mental status alterations, loss of consciousness (LOC), posttraumatic amnesia (PTA), retrograde amnesia (RGA), motor impairments, delayed symptom presentation, and immediate reporting.

Main Results

Concussions from varsity/intercollegiate sports [IPR of 1.73, 95% confidence interval (CI) 1.43–2.10] and intramurals (IPR of 1.53, 95% CI 1.02–2.32) accounted for a larger proportion in males, whereas concussions outside of sport and military activities accounted for a smaller proportion among males (IPR of 0.70, 95% CI 0.58–0.85). The proportion of concussions with prolonged recovery was lower among males (IPR of 0.69, 95% CI 0.60–0.78), while concussions with altered mental status (IPR of 1.23, 95% CI 1.09–1.38), LOC (IPR of 1.67, 95% CI 1.17–2.37), PTA (IPR of 1.94, 95% CI 1.43–2.62), and RGA (IPR of 2.14, 95% CI 1.38–3.31) accounted for a larger proportion among males. A larger proportion of concussions that were immediately reported was observed in males (IPR of 1.15, 95% CI 1.00–2.31). Proportions of other characteristics (e.g., recurrent injuries) were not different between sexes.

Conclusions

A higher proportion of concussions occurred outside of sport and military training for female cadets, who also displayed proportionally longer recovery times than males, despite males demonstrating a higher proportion of LOC, PTA, and RGA. Possible factors may include different mechanisms of injury outside of sport and military training, different biopsychosocial states associated with sex or injury context, and delayed injury reporting when outside of an observed environment, possibly secondary to perceived stigma about reporting injuries.
How Sure is the Driver? Modelling Drivers’ Confidence in Left-Turn Gap Acceptance Decisions
Authors: Bontje Floor , Zgonnikov Arkady
Published: July 2024

When a person makes a decision, it is automatically accompanied by a subjective probability judgment of the decision being correct, in other words, a confidence judgment. A better understanding of the mechanisms responsible for these confidence judgments could provide novel insights into human behavior. However, so far confidence judgments have been mostly studied in simplistic laboratory tasks while little is known about confidence in naturalistic dynamic tasks such as driving. In this study, we made a first attempt of connecting fundamental research on confidence with naturalistic driver behavior. We investigated the confidence of drivers in left-turn gap acceptance decisions in a driver simulator experiment (N = 17). We found that confidence in these decisions depends on the size of the gap to the oncoming vehicle. Specifically, confidence increased with the gap size for trials in which the gap was accepted, and decreased with the gap size for rejected gaps. Similarly to more basic tasks, confidence was negatively related to the response times and correlated with action dynamics during decision execution. Finally, we found that confidence judgments can be captured with an extended dynamic drift–diffusion model. In the model, the drift rate of the evidence accumulator as well as the decision boundaries are functions of the gap size. Furthermore, we demonstrated that allowing for post-decision evidence accumulation in the model increases its ability to describe confidence judgments in rejected gap decisions. Overall, our study confirmed that principles known from fundamental confidence research extend to confidence judgments in dynamic decisions during a naturalistic task.
Aotearoa New Zealand health leader’s opinions on the implementation of a facility-based rehabilitation initiative for older people as an alternative to inpatient rehabilitation in an acute hospital setting
Authors: Barlow-Armstrong Jewel , Ijadi Maghsoodi Abtin , Parsons Matthew , Atherfold Cheryl , Rouse Paul , Walker Cameron
Published: July 2024

Objectives

This study aims to explore the opinions of key health leaders in Aotearoa New Zealand (Waikato Region) regarding a proposed facility-based rehabilitation initiative for older people. The initiative involves a team of health professionals providing intensive rehabilitation up to four times a day, seven days a week, to patients transferred to aged care facilities within the Waikato region.

Method

Structured interviews were conducted across one tertiary hospital, two community facilities, and two aged care facilities in the Waikato region of New Zealand. These were audio recorded and transcribed verbatim to allow for thematic analyses of the transcripts using a (1) general inductive method of inquiry.

Results

Interview transcripts from participants were analysed utilising a general inductive method of enquiry to develop key themes from the transcripts. This followed grounded theory in that themes emerged from the qualitative data collected from participants (2). The three central themes revealed were: "Person-Centered Care: What Matters Most?", "Rehabilitation: Beyond Monday to Friday, Eight to Five," and the importance of a multidisciplinary team working as "integrated partners in care."

All participants supported the implementation of a facility-based rehabilitation initiative and identified key aspects for successful patient outcomes. However, safety was highlighted as a crucial consideration, with participants emphasizing the need for medical support and oversight when implementing such a significant change in the care model.

Conclusion

The study examines Aotearoa New Zealand health leaders' views on implementing a facility-based rehabilitation initiative for older people. It enables readers to consider key factors for successful implementation, addressing acute hospital bed pressures and bridging the gap between acute care, aged care, and home settings.
On the time scales of spectral evolution of nonlinear waves
Authors: Simonis Ashleigh , Hrabski Alexander , Pan Yulin
Published: July 2024

As presented in Annenkov & Shrira (Phys. Rev. Lett., vol. 102, 2009, 024502), when a surface gravity wave field is subjected to an abrupt perturbation of external forcing, its spectrum evolves on a ‘fast’ dynamic time scale of$O(\varepsilon ^{-2})$, with$\varepsilon$a measure of wave steepness. This observation poses a challenge to wave turbulence theory that predicts an evolution with a kinetic time scale of$O(\varepsilon ^{-4})$. We revisit this unresolved problem by studying the same situation in the context of a one-dimensional Majda–McLaughlin–Tabak equation with gravity wave dispersion relation. Our results show that the kinetic and dynamic time scales can both be realised, with the former and latter occurring for weaker and stronger forcing perturbations, respectively. The transition between the two regimes corresponds to a critical forcing perturbation, with which the spectral evolution time scale drops to the same order as the linear wave period (of some representative mode). Such fast spectral evolution is mainly induced by a far-from-stationary state after a sufficiently strong forcing perturbation is applied. We further develop a set-based interaction analysis to show that the inertial-range modal evolution in the studied cases is dominated by their (mostly non-local) interactions with the low-wavenumber ‘condensate’ induced by the forcing perturbation. The results obtained in this work should be considered to provide significant insight into the original gravity wave problem.
Scalable, Coordinated Strategies Leveraging Community Health Workers in Addressing the Adverse and Inequitable Health Effects of Climate Change
Authors: Agahi Massoud , Bartlett Erika , Lawton Betsy , Salehi Cameron
Published: July 2024

Effective climate change resilience in local communities must center each community’s unique challenges and essential role in developing climate resilience strategies. This article will discuss recent developments by the federal government that align with a community-centered approach, and how Community Health Workers can influence the outcomes.
A single-layer band-stop frequency selective surface with wide angular stability property
Authors: Gu Hang , Zhao Wei , Zhang Fan , Yang Chao
Published: July 2024

In this paper, a single-layer band-stop frequency selective surface (FSS) by combination of Mike Kastle unit and square ring unit is proposed to achieve wide angular stable shielding. Owing to the rotational symmetry of the structure, the designed FSS is insensitive to polarization. By the combination design, the wide angular stability can be achieved as the incident angle increases from 0° to 85°, with only a maximum frequency deviation of 0.012 GHz. Meanwhile, the mechanism of the proposed FSS is investigated by the parametric analysis of equivalent circuit model. The prototype was manufactured and measured to verify the design and simulation analysis, and the measurement results were in good agreement with the simulation results.
Seasonality of Retreat Rate of a Wave‐Exposed Marsh Edge
Authors: WinklerPrins Lukas , Lacy Jessica R. , Stacey Mark T. , Logan Joshua B. , Stevens Andrew W.
Published: July 2024

Wave‐driven erosion of marsh boundaries is a major cause of marsh loss, but little research has captured the effect of seasonal differences on marsh‐edge retreat rates to illuminate temporal patterns of when the majority of this erosion is occurring. Using five surface models captured over a study year of a marsh with a steep escarped boundary in South San Francisco Bay, we find a pronounced seasonal signal, where rapid marsh retreat in the spring and summer is driven by a strong sea breeze but little change is found in the marsh‐edge position in the fall and winter. We found accretion in the mudflat transition region close to the marsh boundary in the calmer seasons however, suggesting intertwined morphodynamics of mudflats and the eroding marsh‐scarp. We observed large spatial heterogeneity in retreat rates within seasons, but less on longer (annual and decadal) timescales. The relationship between marsh‐edge retreat rates and properties of the wave field nearby is explored and contextualized against extant relationships, but our results speak to the difficulty in addressing spatial erosion/accretion variability on short (seasonal) timescales with simple models.
China's Ground‐Based Space Environment Monitoring Network—Chinese Meridian Project (CMP)
Authors: Wang Chi , Xu Jiyao , Chen Zhiqing , Li Hui , Feng Xueshang , Huang Zhaohui , Wang Jiangyan
Published: July 2024

Monitoring and investigation of the solar‐terrestrial space environment is a huge challenge for humans in space age. To this end, China has established the Ground‐based Space Environment Monitoring Network, namely Chinese Meridian Project (CMP). The project comprises three major systems: the Space Environment Monitoring System, Data and Communication System, and Scientific Application System. The Space Environment Monitoring System adopts a well‐designed monitoring architecture, known as “One Chain, Three Networks, and Four Focuses,” to achieve stereoscopic and comprehensive monitoring of the entire solar‐terrestrial space. The “One‐Chain” component utilizes optical, radio, interplanetary scintillation, cosmic ray instruments to cover the causal chain of space weather disturbances from the solar surface to near‐Earth space. For the ionosphere, middle and upper atmosphere, and magnetic field, instruments are deployed along longitudes of 120° and 100°E, and latitudes of 30° and 40°N, forming the “Three Networks.” Furthermore, more powerful monitoring facilities or large‐scale instruments have been deployed in four key regions: the high‐latitude polar region, mid‐latitude region in northern China, low‐latitude region at Hainan Island, and the Tibet region. These four regions are crucial for disturbances propagation and evolution, or possess unique geographical and topographical characteristics. The Data and Communication System and Scientific Application System are designed for data collecting, processing, storage, mining, and providing user service based on data acquired by the Space Environment Monitoring System. The data obtained by CMP will be shared with the global scientific community, facilitating enhanced collaboration on space weather and space physics research.
Slab Tear of Subducted Indian Lithosphere Beneath the Eastern Himalayan Syntaxis Region
Authors: Li Ziqing , Zhang Bo , Guo Lei , Hou Zhaoliang , Grasemann Bernhard , Cai Fulong , Wang Houqi
Published: July 2024

In the southeastern Tibetan Plateau, region‐scale dextral strike‐slip shear zones, crucial for India‐Asia convergence, were investigated along the Dulongjiang shear zone near the Eastern Himalayan Syntaxis (EHS). Structural, kinematic, and geochronological data from Dulongjiang and Nabang regions in western Yunnan, China, reveal dextral strike‐slip shearing between 30 and 15 Ma. Various rocks were affected by moderate‐temperature shear deformation (∼450–550°C), inferred from microstructures and quartz CPO patterns, during dextral strike‐slip and exhumation of the shear zone. Combined with structures of pre‐, syn‐, and post‐shearing leucogranites, zircon U‐Pb dating indicates that the dextral shear along the shear zone began in the Early Oligocene (30–29 Ma) subsequent to the India‐Asia collision. Micas in mylonitic granites yield 40Ar/39Ar ages, suggesting that the principal dextral shear deformation occurred approximately between 18 and 15 Ma. The Dulongjiang shear zone is linked to the Parlung, Nabang shear zone, and Sagaing Fault, forming a regional Cenozoic dextral shear system around the EHS. The study, combined with tomographic anomalies beneath the India‐Asia collision zone, highlights distinct lithospheric‐scale evolution in southeastern and eastern Tibet. Continuous intracontinental strike‐slip shearing indicates a tectonic shift from Tibetan extension to block rotation around the EHS. From 30 to 15 Ma, slab tear, accompanied by clockwise rotation and dextral strike‐slip shearing, suggests a warmer geodynamic setting influenced by hot mantle flow associated with ongoing subduction of the Indian lithosphere. Oligocene‐Miocene dextral strike‐slip shearing around the EHS, linking southwards with the Sagaing Fault, may correspond to the rotation necessary for slab to bend, stretch, and eventually tear beneath the region.
Evaluation of a newly developed oral and maxillofacial surgical robotic platform (KD-SR-01) in head and neck surgery: a preclinical trial in porcine models
Authors: Ma Zhongkai , Guo Zhiyong , Ding Zhangfan , Cao Chang , He Jialu , Tang Heyi , Hua Yufei , Hong Jiawei , Shen Qiang , Lubamba Grace Paka , Wang Xiaoyi , Yang Zheng , Zhu Guiquan , Li Chunjie
Published: July 2024

Traditional open head and neck surgery often leaves permanent scars, significantly affecting appearance. The emergence of surgical robots has introduced a new era for minimally invasive surgery. However, the complex anatomy of the head and neck region, particularly the oral and maxillofacial areas, combined with the high costs associated with established systems such as the da Vinci, has limited the widespread adoption of surgical robots in this field. Recently, surgical robotic platform in China has developed rapidly, exemplified by the promise shown by the KangDuo Surgical Robot (KD-SR). Although the KD-SR has achieved some results comparable to the da Vinci surgical robot in urology and colorectal surgery, its performance in complex head and neck regions remains untested. This study evaluated the feasibility, effectiveness, and safety of the newly developed KD-SR-01, comparing it with standard endoscopic systems in head and neck procedures on porcine models. We performed parotidectomy, submandibular gland resection, and neck dissection, collected baseline characteristics, perioperative data, and specifically assessed cognitive workload using the NASA-TLX. None of the robotic procedures were converted to endoscopic or open surgery. The results showed no significant difference in operation time between the two groups (P = 0.126), better intraoperative bleeding control (P = 0.001), and a significant reduction in cognitive workload (P < 0.001) in the robotic group. In conclusion, the KD-SR-01 is feasible, effective, and safe for head and neck surgery. Further investigation through well-designed clinical trials with long-term follow-up is necessary to establish the full potential of this emerging robotic platform.
Rare histological prostate cancer subtypes: Cancer-specific and other-cause mortality
Authors: Siech Carolin , de Angelis Mario , Jannello Letizia Maria Ippolita , Di Bello Francesco , Rodriguez Peñaranda Natali , Goyal Jordan A. , Tian Zhe , Saad Fred , Shariat Shahrokh F. , Puliatti Stefano , Longo Nicola , de Cobelli Ottavio , Briganti Alberto , Hoeh Benedikt , Mandel Philipp , Kluth Luis A. , Chun Felix K. H. , Karakiewicz Pierre I.
Published: July 2024

Background

To assess cancer-specific mortality (CSM) and other-cause mortality (OCM) rates in patients with rare histological prostate cancer subtypes.

Methods

Using the Surveillance, Epidemiology, and End Results database (2004–2020), we applied smoothed cumulative incidence plots and competing risks regression (CRR) models.

Results

Of 827,549 patients, 1510 (0.18%) harbored ductal, 952 (0.12%) neuroendocrine, 462 (0.06%) mucinous, and 95 (0.01%) signet ring cell carcinoma. In the localized stage, five-year CSM vs. OCM rates ranged from 2 vs. 10% in acinar and 3 vs. 8% in mucinous, to 55 vs. 19% in neuroendocrine carcinoma patients. In the locally advanced stage, five-year CSM vs. OCM rates ranged from 5 vs. 6% in acinar, to 14 vs. 16% in ductal, and to 71 vs. 15% in neuroendocrine carcinoma patients. In the metastatic stage, five-year CSM vs. OCM rates ranged from 49 vs. 15% in signet ring cell and 56 vs. 16% in mucinous, to 63 vs. 9% in ductal and 85 vs. 12% in neuroendocrine carcinoma. In multivariable CRR, localized neuroendocrine (HR 3.09), locally advanced neuroendocrine (HR 9.66), locally advanced ductal (HR 2.26), and finally metastatic neuroendocrine carcinoma patients (HR 3.57; all p < 0.001) exhibited higher CSM rates relative to acinar adenocarcinoma patients.

Conclusions

Compared to acinar adenocarcinoma, patients with neuroendocrine carcinoma of all stages and locally advanced ductal carcinoma exhibit higher CSM rates. Conversely, CSM rates of mucinous and signet ring cell adenocarcinoma do not differ from those of acinar adenocarcinoma.
Learning to express reward prediction error-like dopaminergic activity requires plastic representations of time
Authors: Cone Ian , Clopath Claudia , Shouval Harel Z.
Published: July 2024

The dominant theoretical framework to account for reinforcement learning in the brain is temporal difference learning (TD) learning, whereby certain units signal reward prediction errors (RPE). The TD algorithm has been traditionally mapped onto the dopaminergic system, as firing properties of dopamine neurons can resemble RPEs. However, certain predictions of TD learning are inconsistent with experimental results, and previous implementations of the algorithm have made unscalable assumptions regarding stimulus-specific fixed temporal bases. We propose an alternate framework to describe dopamine signaling in the brain, FLEX (Flexibly Learned Errors in Expected Reward). In FLEX, dopamine release is similar, but not identical to RPE, leading to predictions that contrast to those of TD. While FLEX itself is a general theoretical framework, we describe a specific, biophysically plausible implementation, the results of which are consistent with a preponderance of both existing and reanalyzed experimental data.
The type III effector NopL interacts with GmREM1a and GmNFR5 to promote symbiosis in soybean
Authors: Ma Chao , Wang Jinhui , Gao Yongkang , Dong Xulun , Feng Haojie , Yang Mingliang , Yu Yanyu , Liu Chunyan , Wu Xiaoxia , Qi Zhaoming , Mur Luis A. J. , Magne Kévin , Zou Jianan , Hu Zhenbang , Tian Zhixi , Su Chao , Ratet Pascal , Chen Qingshan , Xin Dawei
Published: July 2024

The establishment of symbiotic interactions between leguminous plants and rhizobia requires complex cellular programming activated by Rhizobium Nod factors (NFs) as well as type III effector (T3E)-mediated symbiotic signaling. However, the mechanisms by which different signals jointly affect symbiosis are still unclear. Here we describe the mechanisms mediating the cross-talk between the broad host range rhizobia Sinorhizobium fredii HH103 T3E Nodulation Outer Protein L (NopL) effector and NF signaling in soybean. NopL physically interacts with the Glycine max Remorin 1a (GmREM1a) and the NFs receptor NFR5 (GmNFR5) and promotes GmNFR5 recruitment by GmREM1a. Furthermore, NopL and NF influence the expression of GmRINRK1, a receptor-like kinase (LRR-RLK) ortholog of the Lotus RINRK1, that mediates NF signaling. Taken together, our work indicates that S. fredii NopL can interact with the NF signaling cascade components to promote the symbiotic interaction in soybean.
Efficient molecular doping of polymeric semiconductors improved by coupled reaction
Authors: Pan Jiahao , Wang Jing , Li Kuncai , Dai Xu , Li Qing , Chong Daotong , Chen Bin , Yan Junjie , Wang Hong
Published: July 2024

Exploring chemical doping method to improve the electrical conductivity of polymers is still very attractive for researchers. In this work, we report a developed method of doping a polymer semiconductor aided by the coupled reaction that commonly exists in biological systems where a non-spontaneous reaction is driven by a spontaneous reaction. During the doping process, the chemical reaction between the dopant and the polymer is promoted by introducing a thermodynamically favorable reaction via adding additives that are highly reactive to the reduction product of the dopant to form a coupled reaction, thus significantly improving the electrical conductivity of polymers by 3–7 orders. This coupled reaction doping process shows the potential of wide applications in exploring efficient doping systems to prepare functional conducting polymers, which could be a powerful tool for modern organic electronics.
A safe, effective and adaptable live-attenuated SARS-CoV-2 vaccine to reduce disease and transmission using one-to-stop genome modifications
Authors: Schön Jacob , Barut G. Tuba , Trüeb Bettina Salome , Halwe Nico Joel , Berenguer Veiga Inês , Kratzel Annika , Ulrich Lorenz , Kelly Jenna N. , Brügger Melanie , Wylezich Claudia , Taddeo Adriano , Aguiar Moreira Etori , Túrós Demeter , Grau-Roma Llorenç , Ahrens Ann Kathrin , Schlottau Kore , Britzke Tobias , Breithaupt Angele , Corleis Björn , Kochmann Jana , Oliveira Esteves Blandina I. , Almeida Lea , Thomann Lisa , Devisme Christelle , Stalder Hanspeter , Steiner Silvio , Ochsenbein Sarah , Schmied Kimberly , Labroussaa Fabien , Jores Jörg , V’kovski Philip , Cmiljanovic Vladimir , Alves Marco P. , Benarafa Charaf , Ebert Nadine , Hoffmann Donata , Beer Martin , Thiel Volker
Published: July 2024

Approved vaccines are effective against severe COVID-19, but broader immunity is needed against new variants and transmission. Therefore, we developed genome-modified live-attenuated vaccines (LAV) by recoding the SARS-CoV-2 genome, including ‘one-to-stop’ (OTS) codons, disabling Nsp1 translational repression and removing ORF6, 7ab and 8 to boost host immune responses, as well as the spike polybasic cleavage site to optimize the safety profile. The resulting OTS-modified SARS-CoV-2 LAVs, designated as OTS-206 and OTS-228, are genetically stable and can be intranasally administered, while being adjustable and sustainable regarding the level of attenuation. OTS-228 exhibits an optimal safety profile in preclinical animal models, with no side effects or detectable transmission. A single-dose vaccination induces a sterilizing immunity in vivo against homologous WT SARS-CoV-2 challenge infection and a broad protection against Omicron BA.2, BA.5 and XBB.1.5, with reduced transmission. Finally, this promising LAV approach could be applicable to other emerging viruses.
Fast-moving stars around an intermediate-mass black hole in ω Centauri
Authors: Häberle Maximilian , Neumayer Nadine , Seth Anil , Bellini Andrea , Libralato Mattia , Baumgardt Holger , Whitaker Matthew , Dumont Antoine , Alfaro-Cuello Mayte , Anderson Jay , Clontz Callie , Kacharov Nikolay , Kamann Sebastian , Feldmeier-Krause Anja , Milone Antonino , Nitschai Maria Selina , Pechetti Renuka , van de Ven Glenn
Published: July 2024

Black holes have been found over a wide range of masses, from stellar remnants with masses of 5–150 solar masses (M☉), to those found at the centres of galaxies with M > 105M☉. However, only a few debated candidate black holes exist between 150M☉ and 105M☉. Determining the population of these intermediate-mass black holes is an important step towards understanding supermassive black hole formation in the early universe1,2. Several studies have claimed the detection of a central black hole in ω Centauri, the most massive globular cluster of the Milky Way3–5. However, these studies have been questioned because of the possible mass contribution of stellar mass black holes, their sensitivity to the cluster centre and the lack of fast-moving stars above the escape velocity6–9. Here we report the observations of seven fast-moving stars in the central 3 arcsec (0.08 pc) of ω Centauri. The velocities of the fast-moving stars are significantly higher than the expected central escape velocity of the star cluster, so their presence can be explained only by being bound to a massive black hole. From the velocities alone, we can infer a firm lower limit of the black hole mass of about 8,200M☉, making this a good case for an intermediate-mass black hole in the local universe.
Emergence of large-scale cell death through ferroptotic trigger waves
Authors: Co Hannah K. C. , Wu Chia-Chou , Lee Yi-Chen , Chen Sheng-hong
Published: July 2024

Large-scale cell death is commonly observed during organismal development and in human pathologies1–5. These cell death events extend over great distances to eliminate large populations of cells, raising the question of how cell death can be coordinated in space and time. One mechanism that enables long-range signal transmission is trigger waves6, but how this mechanism might be used for death events in cell populations remains unclear. Here we demonstrate that ferroptosis, an iron- and lipid-peroxidation-dependent form of cell death, can propagate across human cells over long distances (≥5 mm) at constant speeds (around 5.5 μm min−1) through trigger waves of reactive oxygen species (ROS). Chemical and genetic perturbations indicate a primary role of ROS feedback loops (Fenton reaction, NADPH oxidase signalling and glutathione synthesis) in controlling the progression of ferroptotic trigger waves. We show that introducing ferroptotic stress through suppression of cystine uptake activates these ROS feedback loops, converting cellular redox systems from being monostable to being bistable and thereby priming cell populations to become bistable media over which ROS propagate. Furthermore, we demonstrate that ferroptosis and its propagation accompany the massive, yet spatially restricted, cell death events during muscle remodelling of the embryonic avian limb, substantiating its use as a tissue-sculpting strategy during embryogenesis. Our findings highlight the role of ferroptosis in coordinating global cell death events, providing a paradigm for investigating large-scale cell death in embryonic development and human pathologies.
An enterococcal phage-derived enzyme suppresses graft-versus-host disease
Authors: Fujimoto Kosuke , Hayashi Tetsuya , Yamamoto Mako , Sato Noriaki , Shimohigoshi Masaki , Miyaoka Daichi , Yokota Chieko , Watanabe Miki , Hisaki Yuki , Kamei Yukari , Yokoyama Yuki , Yabuno Takato , Hirose Asao , Nakamae Mika , Nakamae Hirohisa , Uematsu Miho , Sato Shintaro , Yamaguchi Kiyoshi , Furukawa Yoichi , Akeda Yukihiro , Hino Masayuki , Imoto Seiya , Uematsu Satoshi
Published: July 2024

Changes in the gut microbiome have pivotal roles in the pathogenesis of acute graft-versus-host disease (aGVHD) after allogenic haematopoietic cell transplantation (allo-HCT)1–6. However, effective methods for safely resolving gut dysbiosis have not yet been established. An expansion of the pathogen Enterococcus faecalis in the intestine, associated with dysbiosis, has been shown to be a risk factor for aGVHD7–10. Here we analyse the intestinal microbiome of patients with allo-HCT, and find that E. faecalis escapes elimination and proliferates in the intestine by forming biofilms, rather than by acquiring drug-resistance genes. We isolated cytolysin-positive highly pathogenic E. faecalis from faecal samples and identified an anti-E. faecalis enzyme derived from E. faecalis-specific bacteriophages by analysing bacterial whole-genome sequencing data. The antibacterial enzyme had lytic activity against the biofilm of E. faecalis in vitro and in vivo. Furthermore, in aGVHD-induced gnotobiotic mice that were colonized with E. faecalis or with patient faecal samples characterized by the domination of Enterococcus, levels of intestinal cytolysin-positive E.faecalis were decreased and survival was significantly increased in the group that was treated with the E. faecalis-specific enzyme, compared with controls. Thus, administration of a phage-derived antibacterial enzyme that is specific to biofilm-forming pathogenic E. faecalis—which is difficult to eliminate with existing antibiotics—might provide an approach to protect against aGVHD.
Plasmacytoid dendritic cells control homeostasis of megakaryopoiesis
Authors: Gaertner Florian , Ishikawa-Ankerhold Hellen , Stutte Susanne , Fu Wenwen , Weitz Jutta , Dueck Anne , Nelakuditi Bhavishya , Fumagalli Valeria , van den Heuvel Dominic , Belz Larissa , Sobirova Gulnoza , Zhang Zhe , Titova Anna , Navarro Alejandro Martinez , Pekayvaz Kami , Lorenz Michael , von Baumgarten Louisa , Kranich Jan , Straub Tobias , Popper Bastian , Zheden Vanessa , Kaufmann Walter Anton , Guo Chenglong , Piontek Guido , von Stillfried Saskia , Boor Peter , Colonna Marco , Clauß Sebastian , Schulz Christian , Brocker Thomas , Walzog Barbara , Scheiermann Christoph , Aird William C. , Nerlov Claus , Stark Konstantin , Petzold Tobias , Engelhardt Stefan , Sixt Michael , Hauschild Robert , Rudelius Martina , Oostendorp Robert A. J. , Iannacone Matteo , Heinig Matthias , Massberg Steffen
Published: July 2024

Platelet homeostasis is essential for vascular integrity and immune defence1,2. Although the process of platelet formation by fragmenting megakaryocytes (MKs; thrombopoiesis) has been extensively studied, the cellular and molecular mechanisms required to constantly replenish the pool of MKs by their progenitor cells (megakaryopoiesis) remains unclear3,4. Here we use intravital imaging to track the cellular dynamics of megakaryopoiesis over days. We identify plasmacytoid dendritic cells (pDCs) as homeostatic sensors that monitor the bone marrow for apoptotic MKs and deliver IFNα to the MK niche triggering local on-demand proliferation and maturation of MK progenitors. This pDC-dependent feedback loop is crucial for MK and platelet homeostasis at steady state and under stress. pDCs are best known for their ability to function as vigilant detectors of viral infection5. We show that virus-induced activation of pDCs interferes with their function as homeostatic sensors of megakaryopoiesis. Consequently, activation of pDCs by SARS-CoV-2 leads to excessive megakaryopoiesis. Together, we identify a pDC-dependent homeostatic circuit that involves innate immune sensing and demand-adapted release of inflammatory mediators to maintain homeostasis of the megakaryocytic lineage.
Silencing CK19 regulates ferroptosis by affecting the expression of GPX4 and ACSL4 in oral squamous cell carcinoma in vivo and in vitro
Authors: Rao Yong , Li Jingying , Shi Lijuan , Chen Xiao , Hu Yun , Mao Yalin , Zhang Xiaoyan , Liu Xuqian
Published: July 2024

To analyze the mechanism of how interfering with the cytokeratin 19 (CK19) pathway via the ferroptosis pathway affects tumor biological behaviors in the process of oral squamous cell carcinoma (OSCC) development. TCGA was used to analyze the expression of CK19 in pan-cancer and head and neck squamous cell carcinoma (HNSC) and to explore the ferroptosis-related genes related to HNSC. The effect of silencing CK19 on the migration ability of HSC-4 cells was verified by wound healing and migration assay. HSC-4 cells with silencing of CK19 and tumor-bearing nude mouse model were constructed. RT-qPCR, immunofluorescence and western blot were used to analyze the expression of ferroptosis-related genes. CK19 is highly expressed in human OSCC and nude mice. The migration ability of cells in the CK19-silenced group was lower than that of the control group. In vivo and in vitro, CK19 was negatively correlated with the expression of ACSL4 and positively correlated with the expression of GPX4. Compared with the control group, GPX4 expression was down-regulated and ACSL4 expression was up-regulated in the CK19-silenced group. Silencing CK19 also increased intracellular Fe2+ content and MDA content. Silencing CK19 can affect the expression of GPX4 and ACSL4 to regulate ferroptosis and at the same time increase the content of MDA, Fe2+ and ROS levels, thereby activating the regulation of ferroptosis pathway in the development of OSCC.
Retinal hyperspectral imaging in mouse models of Parkinson’s disease and healthy aging
Authors: Trlin Paul , Gong Jenny , Tran Katie K. N. , Wong Vickie H. Y. , Lee Pei Ying , Hoang Anh , Zhao Da , Beauchamp Leah C. , Lim Jeremiah K. H. , Metha Andrew , Barnham Kevin J. , Finkelstein David I. , Bui Bang V. , Bedggood Phillip , Nguyen Christine T. O.
Published: July 2024

Retinal hyperspectral imaging (HSI) is a non-invasive in vivo approach that has shown promise in Alzheimer’s disease. Parkinson’s disease is another neurodegenerative disease where brain pathobiology such as alpha-synuclein and iron overaccumulation have been implicated in the retina. However, it remains unknown whether HSI is altered in in vivo models of Parkinson’s disease, whether it differs from healthy aging, and the mechanisms which drive these changes. To address this, we conducted HSI in two mouse models of Parkinson’s disease across different ages; an alpha-synuclein overaccumulation model (hA53T transgenic line M83, A53T) and an iron deposition model (Tau knock out, TauKO). In comparison to wild-type littermates the A53T and TauKO mice both demonstrated increased reflectivity at short wavelengths ~ 450 to 600 nm. In contrast, healthy aging in three background strains exhibited the opposite effect, a decreased reflectance in the short wavelength spectrum. We also demonstrate that the Parkinson’s hyperspectral signature is similar to that from an Alzheimer’s disease model, 5xFAD mice. Multivariate analyses of HSI were significant when plotted against age. Moreover, when alpha-synuclein, iron or retinal nerve fibre layer thickness were added as a cofactor this improved the R2 values of the correlations in certain groups. This study demonstrates an in vivo hyperspectral signature in Parkinson’s disease that is consistent in two mouse models and is distinct from healthy aging. There is also a suggestion that factors including retinal deposition of alpha-synuclein and iron may play a role in driving the Parkinson’s disease hyperspectral profile and retinal nerve fibre layer thickness in advanced aging. These findings suggest that HSI may be a promising translation tool in Parkinson’s disease.
Immune cells phenotype and bioenergetic measures in CD4+ T cells differ between high and low feed efficient dairy cows
Authors: Arshad Usman , Kennedy Katherine M. , Cid de la Paz Malena , Kendall Sophia J. , Cangiano Lautaro R. , White Heather M.
Published: July 2024

Identifying sources of variance that contribute to residual feed intake (RFI) can aid in improving feed efficiency. The objectives of this study were to investigate immune cells phenotype and bioenergetic measures in CD4+ T cells in low feed efficient (LE) and high feed efficient (HE) dairy cows. Sixty-four Holstein cows were enrolled at 93 ± 22 days in milk (DIM) and monitored for 7 weeks to measure RFI. Cows with the highest RFI (LE; n = 14) or lowest RFI (HE; n = 14) were selected to determine immune cells phenotype using flow cytometry. Blood was sampled in the same LE and HE cows at 234 ± 22 DIM to isolate peripheral blood mononuclear cells, followed by magnetic separation of CD4+ T lymphocytes using bovine specific monoclonal antibodies. The metabolic function of isolated CD4+ T lymphocytes was evaluated under resting and activated states. An increased expression of CD62L+ cells within CD8+ T lymphocytes and CD21+ B lymphocytes was observed in HE cows compared to LE cows. CD4+ T lymphocytes of HE cows exhibited an increased mitochondrial and glycolytic activity in resting and activated states compared to LE cows. These data suggest that immune cells in HE cows exhibit an increased metabolic function, which might influence nutrient partitioning and utilization and serve as a source of variation in feed efficiency that warrants future investigation.
Mice integrate conspecific and contextual information in forming social episodic-like memories under spontaneous recognition task conditions
Authors: Ross T. W. , Poulter S. L. , Lever C. , Easton A.
Published: July 2024

The ability to remember unique past events (episodic memory) may be an evolutionarily conserved function, with accumulating evidence of episodic-(like) memory processing in rodents. In humans, it likely contributes to successful complex social networking. Rodents, arguably the most used laboratory models, are also rather social animals. However, many behavioural paradigms are devoid of sociality, and commonly-used social spontaneous recognition tasks (SRTs) are open to non-episodic strategies based upon familiarity. We address this gap by developing new SRT variants. Here, in object-in-context SRTs, we asked if context could be specified by the presence/absence of either a conspecific (experiment 1) or an additional local object (experiment 2). We show that mice readily used the conspecific as contextual information to distinguish unique episodes in memory. In contrast, no coherent behavioural response emerged when an additional object was used as a potential context specifier. Further, in a new social conspecific-in-context SRT (experiment 3) where environment-based change was the context specifier, mice preferably explored a more recently-seen familiar conspecific associated with contextual mismatch, over a less recently-seen familiar conspecific presented in the same context. The results argue that, in incidental SRT conditions, mice readily incorporate conspecific cue information into episodic-like memory. Thus, the tasks offer different ways to assess and further understand the mechanisms at work in social episodic-like memory processing.
Application of Newton’s polynomial interpolation scheme for variable order fractional derivative with power-law kernel
Authors: Naveen S , Parthiban V
Published: July 2024

This paper, offers a new method for simulating variable-order fractional differential operators with numerous types of fractional derivatives, such as the Caputo derivative, the Caputo–Fabrizio derivative, the Atangana–Baleanu fractal and fractional derivative, and the Atangana–Baleanu Caputo derivative via power-law kernels. Modeling chaotical systems and nonlinear fractional differential equations can be accomplished with the utilization of variable-order differential operators. The computational structures are based on the fractional calculus and Newton’s polynomial interpolation. These methods are applied to different variable-order fractional derivatives for Wang–Sun, Rucklidge, and Rikitake systems. We illustrate this novel approach’s significance and effectiveness through numerical examples.
Moderate aerobic training enhances the effectiveness of insulin therapy through hypothalamic IGF1 signaling in rat model of Alzheimer's disease
Authors: Radfar Forough , Shahbazi Mehdi , Tahmasebi Boroujeni Shahzad , Arab Ameri Elahe , Farahmandfar Maryam
Published: July 2024

Alzheimer's disease (AD) is a neurological condition that is connected with a decline in a person's memory as well as their cognitive ability. One of the key topics of AD research has been the exploration of metabolic causes. We investigated the effects of treadmill exercise and intranasal insulin on learning and memory impairment and the expression of IGF1, BDNF, and GLUT4 in hypothalamus. The animals were put into 9 groups at random. In this study, we examined the impact of insulin on spatial memory in male Wistar rats and analyzed the effects of a 4-week pretreatment of moderate treadmill exercise and insulin on the mechanisms of improved hypothalamic glucose metabolism through changes in gene and protein expression of IGF1, BDNF, and GLUT4. We discovered that rat given Aβ25–35 had impaired spatial learning and memory, which was accompanied by higher levels of Aβ plaque burden in the hippocampus and lower levels of IGF1, BDNF, and GLUT4 mRNA and protein expression in the hypothalamus. Additionally, the administration of exercise training and intranasal insulin results in the enhancement of spatial learning and memory impairments, the reduction of plaque burden in the hippocampus, and the enhancement of the expression of IGF1, BDNF, and GLUT4 in the hypothalamus of rats that were treated with Aβ25–35. Our results show that the improvement of learning and spatial memory due to the improvement of metabolism and upregulation of the IGF1, BDNF, and GLUT4 pathways can be affected by pretreatment exercise and intranasal insulin.
PRDM6 promotes medulloblastoma by repressing chromatin accessibility and altering gene expression
Authors: Schmidt Christin , Cohen Sarah , Gudenas Brian L. , Husain Sarah , Carlson Annika , Westelman Samantha , Wang Linyu , Phillips Joanna J. , Northcott Paul A. , Weiss William A. , Schwer Bjoern
Published: July 2024

SNCAIP duplication may promote Group 4 medulloblastoma via induction of PRDM6, a poorly characterized member of the PRDF1 and RIZ1 homology domain-containing (PRDM) family of transcription factors. Here, we investigated the function of PRDM6 in human hindbrain neuroepithelial stem cells and tested PRDM6 as a driver of Group 4 medulloblastoma. We report that human PRDM6 localizes predominantly to the nucleus, where it causes widespread repression of chromatin accessibility and complex alterations of gene expression patterns. Genome-wide mapping of PRDM6 binding reveals that PRDM6 binds to chromatin regions marked by histone H3 lysine 27 trimethylation that are located within, or proximal to, genes. Moreover, we show that PRDM6 expression in neuroepithelial stem cells promotes medulloblastoma. Surprisingly, medulloblastomas derived from PRDM6-expressing neuroepithelial stem cells match human Group 3, but not Group 4, medulloblastoma. We conclude that PRDM6 expression has oncogenic potential but is insufficient to drive Group 4 medulloblastoma from neuroepithelial stem cells. We propose that both PRDM6 and additional factors, such as specific cell-of-origin features, are required for Group 4 medulloblastoma. Given the lack of PRDM6 expression in normal tissues and its oncogenic potential shown here, we suggest that PRDM6 inhibition may have therapeutic value in PRDM6-expressing medulloblastomas.