bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparative evaluation of efficacy of 2% lidocaine containing adrenaline with and without hyaluronidase in inferior alveolar nerve blocks for patients requiring bilateral mandibular extractions
Authors: Lunkad Piyush , Shah Sonal , Rudagi Bhimappa , Mehta Mili , Bhagat Bhushan , Ticku Smriti
Published: January 2024

Purpose

To evaluate and compare the efficacy of 2% lidocaine containing adrenaline with and without hyaluronidase in inferior alveolar nerve blocks for patients requiring bilateral mandibular extractions.

Patients and Methods

This was the split‐mouth study conducted on 26 patients requiring bilateral mandibular teeth extraction. All the patients were assigned randomly to one of the two groups: (i) 2% lignocaine HCl + 1:2,00,000 adrenaline + hyaluronidase (75 IU) solution will be administered on one side which is the experimental side and (ii) 2% lignocaine HCl + 1:2,00,000 adrenaline solution on the other side is control side. In the first session, the patients randomly received the inferior alveolar nerve block with or without hyaluronidase in one side of the oral cavity. One week later, the same patient received the other technique which was not received in the first session. We also evaluated the onset, duration and need of any supplementary anaesthesia in both the groups.

Results

Comparison of VAS score in the control group (2.73 ± 0.724) and experimental group (3 ± 0.693) showed statistically insignificant results (p = 0.177). Whereas the onset of local anaesthesia showed a statistically significant difference between the two groups (p < 0.001) mean of control group (2.73 ± 0.47) and experimental group (1.15 ± 0.23). Comparison of duration of anaesthesia showed a statistically significant difference (p < 0.001) with the mean duration of the experimental group being higher (106 ± 7.94) than the control group (86.27 ± 3.90). Comparison for the need for supplementary anaesthesia showed no statistically significant difference between the two groups.

Conclusion

We conclude that if hyaluronidase is used, better blocks with smaller volumes are produced. LAs with hyaluronidase have been shown to improve the quality and effectiveness of anaesthetic blocks and shorten the time it takes for anaesthesia to begin, accelerate the onset of akinesia and lessen the need for additional anaesthesia. It also increases the duration of anaesthesia.
Autosomal recessive congenital ichthyosis due to novel CYP4F22 mutation presenting with a collodion membrane and ocular manifestations
Authors: Swink Shane M. , Hurley Margaret , Haynes Dylan , Larijani Mary
Published: January 2024

Autosomal recessive congenital ichthyoses (ARCI) are a range of genetic disorders of keratinization. The rare CYP4F22 gene mutation can present with or without collodion membrane at birth and leads to the development of mild ichthyosis phenotype. We report a case of a novel pathogenic CYP4F22 genetic mutation presenting with collodion membrane and ocular manifestations. Ocular manifestations have recently been reported in a patient with ARCI with known CYP4F22 mutation, which further supports a possible correlation between the CYP4F22 mutation and this distinct phenotype.
The first intron of EIJ1 confers a specific response to wounding and herbivore stresses
Authors: Yin M. , Li Y. , Liu H.
Published: January 2024

Plants are constantly exposed to different kinds of biotic stress, such as herbivore attack and wounding. To deal with these stresses, plants have evolved sophisticated defence mechanisms to protect themselves.

Previously, we found that EIJ1 (EDS1‐interacting J protein 1) plays a negative regulatory role in plant disease resistance in Arabidopsis thaliana. Follow‐up studies revealed that EIJ1 specifically responds to wounding and herbivore stresses. The expression of EIJ1 was specifically induced by wounding or herbivore stress, as demonstrated by similar results in EIJ1 protein assay.

Interestingly, GUS staining found that the promoter of EIJ1 is not involved in the induction of expression under wounding stress. Instead, we identified the first intron of EIJ1 as a key factor in response to wounding stress. Deleting the first intron of EIJ1 resulted in a loss of response to wounding stress in plants.

Our results broaden the role of EIJ1 in plant resistance to biotic stress and provide new insights into plant responses to biotic stress.
Antioxidant and Secondary Metabolite Responses in Wheat under Cereal Leaf Beetle (Oulema melanopus L.) Infestation
Authors: Parthiban Manikannan , Jan Farkhandah , Mantoo Mohammad Ayuob , Kaur Satinder , Rustgi Sachin , Wani Fehim Jeelani , Varshney Rajeev Kumar , Mir Reyazul Rouf
Published: January 2024

Wheat is one of the most important cereal crops grown in the Western Himalayas of India but its production is challenged by the insect “cereal leaf beetle (CLB)”. This study explores the impact of domestication and modern crop improvement on wheat's defense mechanisms against the CLB, a global threat to wheat cultivation. Sixteen diverse wheat genotypes having different ploidy levels were investigated, including wild wheat, landraces, mutants, advanced breeding lines, commercial varieties, and a Rye grass genotype. Genotypes with resistance genes, landraces, and wild wheat exhibited the lowest CLB infestation and oxidative damage. These genotypes displayed enhanced antioxidant enzyme activity, such as peroxidase (POD), ascorbate peroxidase (APX), catalase (CAT), superoxide dismutase (SOD), and polyphenol oxidase (PPO), reduced reactive oxygen species (ROS) production, and increased plant secondary metabolite (phenol and tannin) production upon CLB infestation. Resistant durum wheat demonstrated moderate responses and exhibited higher levels of flavonoid production. On the other hand, susceptible durum wheat genotypes, commercial variety Shalimar Wheat‐02 (SW‐2), showed high CLB infestation, ROS production, reduced antioxidant enzyme and secondary metabolite production. This may be because modern varieties like SW‐2 were not selected for insect resistance. These findings emphasize the significance of preserving genetic diversity from wild wheat and landraces to bolster wheat breeding programs against pests such as CLB. This study underscores the need to harness ancestral wheat lines to enhance insect pest resistance in modern wheat cultivars.
Transfer seeds, hay, or soil blocks? The importance of the completeness of biological inputs to address dispersal and establishment limitations during the restoration of plant assemblages in floodplain grasslands
Authors: Garrouj Myriam , Alard Didier , Dudit Jennifer , Benot Marie‐Lise
Published: January 2024

This study investigated different techniques of grassland restoration to overcome dispersal or establishment limitation, which are key processes influencing early‐successional plant community assembly. A fully randomized in situ experiment was set up in a former arable land in a floodplain along the Garonne river (south‐western France) to test for the effect of (1) the type and completeness of the biological input (any biological material—seed, hay, and soil—transferred to the site under restoration), (2) soil disturbance by deep tillage, and (3) their interaction on plant community dynamics for 5 years. All inputs influenced the plant community structure and composition. The effects depended on the type of the input but not necessarily in link with its completeness. High density and diversity seed mixture led to high levels of richness and relative abundance of target species like soil blocks, the input considered as the most complete. During the first year, hay transfer mostly influenced community assembly through negative litter effects. Delayed germination of several species contributed to buffer these early effects. This study supports the importance of dispersal limitation during early succession in degraded grassland ecosystems whereas soil disturbance had only subtle effects on the seed bank and standing plant community, indicating that competition and establishment limitation were of secondary importance in our study system. Our results suggest that even low‐frequency immigration events (e.g. when a few seeds are transferred within hay) can be of great importance providing that a sufficiently long time period is considered for grassland restoration.
Insurance and the public–private management of risk at US commercial nuclear power plants
Authors: Gudgel John E.
Published: January 2024

This article examines the public–private partnership between the federal government, private insurers, and power companies that enabled the development of commercial nuclear power generation during the 1950s and its evolution to the present day. The public–private process of nuclear insurance development and its impact on nuclear safety is examined through the lens of the Price–Anderson Act enactment and subsequent renewals. The purpose is to show how commercial nuclear insurance evolved over time, and how the indemnification of potentially catastrophic losses influenced the safety behavior of operators, regulators, and other institutions. Evidence is presented demonstrating the relationship between nuclear insurance and safety, using insurance liability and property premiums, and key measures of nuclear safety.
“Following Our Own Path”: Pavel Katenin’s Political Theater
Authors: New Katherine
Published: January 2024

The present article focuses on the tension arising from Pavel Katenin’s aesthetic and literary vision for the reception of Antiquity in Russian mythological drama: his avid support of Classical purism and his denunciation of dramatists, for whom ancient myths served merely as a resource of historical parallels, is challenging to reconcile with the revolutionary conception of his play Andromache. The paper argues that Katenin regarded antiquity as an idealized universe from which numerous motifs could be drawn for inspiration. Semantic and structural means employed in the tragedy are analyzed as shedding light on the extent of Katenin’s transformation of the ancient myth to reflect the ideology of his time. The paper suggests that Classical antiquity served as a “mask,” allowing contemporary Decembrist circles to apply ancient models and situational resolutions to their own political crises. The dramatist’s conflation of masked political ideology with extreme innovation and intricate intertextual allusion is put forward as a cause of the brevity of the stage life that Katenin’s Andromache was allowed in St. Petersburg’s Bolshoi Theater.
Differentiation and risk stratification of basal cell carcinoma with deep learning on histopathologic images and measuring nuclei and tumor microenvironment features
Authors: Lan Xuemei , Guo Guanchen , Wang Xiaopo , Yan Qiao , Xue Ruzeng , Li Yufen , Zhu Jiaping , Dong Zhengbang , Wang Fei , Li Guomin , Wang Xiangxue , Xu Jun , Jiang Yiqun
Published: January 2024

Background

Nuclear pleomorphism and tumor microenvironment (TME) play a critical role in cancer development and progression. Identifying most predictive nuclei and TME features of basal cell carcinoma (BCC) may provide insights into which characteristics pathologists can use to distinguish and stratify this entity.

Objectives

To develop an automated workflow based on nuclei and TME features from basaloid cell tumor regions to differentiate BCC from trichoepithelioma (TE) and stratify BCC into high‐risk (HR) and low‐risk (LR) subtypes, and to identify the nuclear and TME characteristics profile of different basaloid cell tumors.

Methods

The deep learning systems were trained on 161 H&E ‐stained sections which contained 51 sections of HR‐BCC, 50 sections of LR‐BCC and 60 sections of TE from one institution (D1), and externally and independently validated on D2 (46 sections) and D3 (76 sections), from 2015 to 2022. 60%, 20% and 20% of D1 data were randomly splitted for training, validation and testing, respectively. The framework comprised four stages: tumor regions identification by multi‐head self‐attention (MSA) U‐Net, nuclei segmentation by HoVer‐Net, quantitative feature by handcrafted extraction, and differentiation and risk stratification classifier construction. Pixel accuracy, precision, recall, dice score, intersection over union (IoU) and area under the curve (AUC) were used to evaluate the performance of tumor segmentation model and classifiers.

Results

MSA‐U‐Net model detected tumor regions with 0.910 precision, 0.869 recall, 0.889 dice score and 0.800 IoU. The differentiation classifier achieved 0.977 ± 0.0159, 0.955 ± 0.0181, 0.885 ± 0.0237 AUC in D1, D2 and D3, respectively. The most discriminative features between BCC and TE contained Homogeneity, Elongation, T‐T_meanEdgeLength, T‐T_Nsubgraph, S‐T_HarmonicCentrality, S‐S_Degrees. The risk stratification model can well predict HR‐BCC and LR‐BCC with 0.920 ± 0.0579, 0.839 ± 0.0176, 0.825 ± 0.0153 AUC in D1, D2 and D3, respectively. The most discriminative features between HR‐BCC and LR‐BCC comprised IntensityMin, Solidity, T‐T_minEdgeLength, T‐T_Coreness, T‐T_Degrees, T‐T_Betweenness, S‐T_Degrees.

Conclusions

This framework hold potential for future use as a second opinion helping inform diagnosis of BCC, and identify nuclei and TME features related with malignancy and tumor risk stratification.
Wemap‐based direction model for individuals with limited spatial orientation skills
Authors: Wang Xiaolong , Yan Haowen , Wang Zhuo , Gao Xiaorong
Published: January 2024

Spatial direction relationships act as links between visually perceived data and natural language in cartography and geographic information systems. Although the existing direction models are able to compute spatial direction relationships, their adaptability to unique users of Wemap, such as individuals with limited spatial orientation skills (ILSOS), is minimal. In particular, the ability to identify locations and directions on maps can pose serious challenges for ILSOS. As such, a Wemap‐based direction model was developed in this study to address this deficiency, specifically targeting ILSOS. To address these challenges, a model for calculating spatial direction relationships was constructed. Subsequently, a questionnaire was administered to verify the consistency of the proposed model with the spatial perceptions of ILSOS. The experimental results demonstrate that (1) the proposed model can calculate the spatial direction relationships between a reference object and source target based on absolute reference frames; (2) ILSOS account for a certain proportion of the population and have a superior ability to distinguish spatial over geographic directions; and (3) the calculation results of the proposed model are consistent with the spatial cognition of ILSOS.
Lies Have Short Legs: Brazilian Media Exposes Bolsonaro's Deceptive Claims Amidst Misinformation Surge
Authors: Vieira Adriana Barsotti , Aguiar Leonel Azevedo de
Published: January 2024

In an era marked by widespread misinformation and declining trust in institutions and journalism, the deceptive statements made by former Brazilian president Jair Bolsonaro have gained significant attention. However, it was only in the second year of his term, during the COVID-19 pandemic, that news outlets actively began to expose and denounce his false and misleading claims. This article presents a content analysis comparing press coverage of the following four pivotal moments in the Bolsonaro administration during the pandemic: his speech at the UN General Assembly in 2020, his national radio and TV address in March 2021, his speech to ambassadors in July 2022, and his interview with Jornal Nacional, the most-watched news program in Brazil, in August 2022. By examining articles and headlines from the country's three most prominent newspapers, including two leading fact-checking agencies, this study reveals a shift in media discourse with the term 'lie' being increasingly used. Our hypothesis is that journalism is striving to reclaim its role as a trustworthy institution.
The Roles of Social Media and Traditional News Media in Promoting Government Responsiveness in Social Incidents
Authors: Yuan Lihong , Mohammad Razi Siti Aishah Binti Hj , Mahamed Mastura , Binti Kasimon Diyana Nawar
Published: January 2024

Social media is considered to play an important role in promoting government responsiveness. However, it is impossible for the government to respond to all issues in the actual situation. Especially when encountering controversial social incidents, the local government usually evades responsibility due to damage to reputation or interests. This paper argues that when a controversial social incident occurs in China, the traditional news media will work with social media to encourage the local government to respond. Three cases are selected according to the hot discussion index of Sina Weibo, China's largest social media platform for multiple-case studies. 21 participants were interviewed to explore the function of social media and traditional news media during the process of government responsiveness. The results showed that traditional news media played the role of professionalism, supervision, and broker to develop social incidents. And social media took the information aggregation part in most situations. Social media and traditional news media work together to promote the local government to make government responsiveness active.
Laser-Structured Thin Film Sensor Technology for Sliding Bearings in Internal Combustion Engines
Authors: Kiesling Constantin , Marques da Silva Matheus , Kober Martin , Wimmer Andreas , Düsing Jan , Hager Gunther
Published: January 2024

Global issues such as climate change, environmental pollution, and conservation of resources require manufacturers of internal combustion engines (ICE) to achieve substantially reduced emissions of greenhouse gases and pollutants as well as increased engine efficiency and durability. Condition monitoring and predictive maintenance approaches for sliding bearings in ICEs are key tools for increasing engine durability and saving resources by exploiting more of the useful lifetime of a bearing while avoiding critical engine operation caused by bearing wear and failure. These approaches require appropriate measurement technology capable of acquiring informative parameters that reflect the current condition of the bearings while withstanding the high temperatures and mechanical loads encountered inside the engine and accommodating spatial constraints. This paper deals with research work related to advanced sensor technology that is highly integrated into sliding bearings so that information is obtained nearly directly from relevant areas such as the bearing running layer and the lubrication gap. An isolated, sputtered sensor layer with a thickness of a few micrometers is employed in combination with a laser structuring process to form the desired thin film sensor structure below the bearing running surface. While several measurement parameters and corresponding sensor types are conceivable, this paper focuses on temperature and strain measurements that rely on a change in the electrical resistance of the sensor layer material. Promising sensor layouts and positions targeted for use in condition monitoring applications in ICEs are elaborated in detail. Developments and challenges in implementing the sensor technology concept—in particular with regard to the process of manufacturing the sensor as well as the wire contacting—are outlined in depth. The paper concludes by presenting measurement results obtained with this sensor technology at lab scale as well as an outlook toward implementing the instrumented bearings in ICEs.
Variability of External Load Measures During Soccer Match Play: Influence of Player Fitness or Pacing?
Authors: Rabbani Alireza , Ermidis Giorgios , Clemente Filipe Manuel , Twist Craig
Published: January 2024

Purpose: The aims of this study were to examine the variability of selected external load metrics within 15-minute intervals during soccer match play and examine their relationship with players’ high-intensity intermittent fitness. Methods: A total of 18 male soccer players were monitored for their external load metrics during 26 matches, which included total distance, high-metabolic-load distance, and mechanical work (defined as the sum of accelerations and decelerations >3 m2). Additionally, players completed the 30-15 Intermittent Fitness Test. Results: Total distance had lower coefficients of variation than high-metabolic-load distance and mechanical work (effect size [ES]: 5.2 to 6.4; very large). Within-player Δ-15min showed moderate to large decreases (ES: −0.7 to −1.6) and increases (ES: 0.9 to 1.8) in absolute and coefficient-of-variation values, respectively. Large relationships (r = .55 to .61) were observed between the Intermittent Fitness Test and 15-minmean and 15-minbest in all selected external load metrics. However, small to moderate (0.27 to 0.41) associations were observed between the Intermittent Fitness Test and Δ-15min in selected external load metrics. Conclusions: These findings suggest that players with relatively lower intermittent running capacity might show lower variability during matches, as evidenced by smaller reductions in high-intensity actions during the final 15 minutes. We attribute these observations to players’ possessing better pacing strategies.
The Pedagogization of Traditional Indigenous Games in Canada, Australia, and Aotearoa New Zealand
Authors: Fabian Tom , Rynne Steven , Hapeta Jeremy , Giles Audrey R.
Published: January 2024

Pedagogization can be understood as an umbrella term for increased educational action. In settler-colonial contexts, the pedagogization of traditional Indigenous games has gained traction in recent years. As noted by a number of academic studies, traditional games have been used in efforts to promote cultural connectedness, inclusion, and engagement and address social justice in physical education programs. This commentary aims to survey the pedagogization of traditional Indigenous games in Canada, Australia, and Aotearoa New Zealand. We argue, with cautious optimism, that traditional Indigenous games may act as a conduit for more culturally relevant physical education curricula and reconciliatory pedagogical training for physical education teachers.
School Administrators’ Perspectives on and Support for Physical Education
Authors: Kinder Christopher J. , McNamara Scott W.T. , Woods Amelia Mays , Mueller Alexandra , Ryba Kacper , Richards Kevin Andrew
Published: January 2024

Purpose: The socialization literature has identified the importance of school administrator support in physical education teachers’ work experiences. The purpose of this study was to understand how principals’ own socialization influences their perspectives on and support for physical education. Methods: Data were collected through semistructured interviews with 29 school principals (14 males and 15 females) and 15 physical educators (11 males and four females) matched at the schools from which principals were recruited. Results: Qualitative data analysis resulted in four intersecting themes: (a) Administrators’ prior socialization and subjective theories frame support for physical education; (b) supportive principals are visible, engage with their teachers, and hold them accountable; (c) stress is exacerbated when principals and physical educators’ values and beliefs differ; and (d) school and policy constraints influence administrators’ vision and support for physical education. Discussion and Conclusion: Educational leadership programs should consider preparing principals to support the work of physical education teachers.
Effects of Static Hamstring Stretching on Maximal Sprint Speed and Relationship With Nordic Hamstring Strength
Authors: Ozaki Yusuke , Ueda Takeshi
Published: January 2024

This study aimed to determine the acute effects of static stretching of the hamstrings on maximal sprint speed and its spatiotemporal variables and lower-limb kinematics during the late swing phase, as well as the relationship with Nordic hamstring strength. The study had a within-participant experimental design. Sixteen healthy male college sprinters were asked to sprint 80 m without static stretching and with static stretching of the hamstrings for 4 × 30 s per leg before the sprint; both conditions were counterbalanced. The knee flexion peak torque was measured using the Nordic hamstring. The differences between no static stretching and static stretching as well as their relationship with Nordic hamstring strength were investigated. The results showed that the touchdown distance (p = .036) significantly increased following static stretching. Although not significant, maximal sprint speed decreased (p = .086), and the theoretical hamstring length (difference between knee angle and hip angle) at ipsilateral touchdown was greater (p = .069) following static stretching. In addition, a lower peak torque of the Nordic hamstring resulted in a more significant decrease in maximal sprint speed following static stretching. Therefore, static stretching of the hamstring just before sprinting may increase the theoretical hamstring length during the late swing phase at maximal sprint speed and induce kinematics that increases the hamstring strain injury risk. Moreover, it is suggested that improving the Nordic hamstring strength may help minimize the negative effects of static stretching on the hamstrings.
RREB1 regulates neuronal proteostasis and the microtubule network
Authors: Griffin Emily N. , Jucius Thomas , Sim Su-Eon , Harris Belinda S. , Heinz Sven , Ackerman Susan L.
Published: January 2024

Transcription factors play vital roles in neuron development; however, little is known about the role of these proteins in maintaining neuronal homeostasis. Here, we show that the transcription factor RREB1 (Ras-responsive element-binding protein 1) is essential for neuron survival in the mammalian brain. A spontaneous mouse mutation causing loss of a nervous system–enriched
Rreb1
transcript is associated with progressive loss of cerebellar Purkinje cells and ataxia. Analysis of chromatin immunoprecipitation and sequencing, along with RNA sequencing data revealed dysregulation of RREB1 targets associated with the microtubule cytoskeleton. In agreement with the known role of microtubules in dendritic development, dendritic complexity was disrupted in
Rreb1
-deficient neurons. Analysis of sequencing data also suggested that RREB1 plays a role in the endomembrane system. Mutant Purkinje cells had fewer numbers of autophagosomes and lysosomes and contained P62- and ubiquitin-positive inclusions. Together, these studies demonstrate that RREB1 functions to maintain the microtubule network and proteostasis in mammalian neurons.
Keeping time and rhythm by internal simulation of sensory stimuli and behavioral actions
Authors: de Lafuente Victor , Jazayeri Mehrdad , Merchant Hugo , García-Garibay Otto , Cadena-Valencia Jaime , Malagón Ana M.
Published: January 2024

Effective behavior often requires synchronizing our actions with changes in the environment. Rhythmic changes in the environment are easy to predict, and we can readily time our actions to them. Yet, how the brain encodes and maintains rhythms is not known. Here, we trained primates to internally maintain rhythms of different tempos and performed large-scale recordings of neuronal activity across the sensory-motor hierarchy. Results show that maintaining rhythms engages multiple brain areas, including visual, parietal, premotor, prefrontal, and hippocampal regions. Each recorded area displayed oscillations in firing rates and oscillations in broadband local field potential power that reflected the temporal and spatial characteristics of an internal metronome, which flexibly encoded fast, medium, and slow tempos. The presence of widespread metronome-related activity, in the absence of stimuli and motor activity, suggests that internal simulation of stimuli and actions underlies timekeeping and rhythm maintenance.
Universal pictures: A lithophane codex helps teenagers with blindness visualize nanoscopic systems
Authors: Alonzo Emily A. , Lato Travis J. , Gonzalez Mayte , Olson Trevor L. , Savage Quentin R. , Garza Levi N. , Green Morgan T. , Koone Jordan C. , Cook Noah E. , Dashnaw Chad M. , Armstrong Darren B. , Wood John L. , Garbrecht Lisa S. , Haynes Madeline L. , Jacobson Miriam R. , Guberman-Pfeffer Matthew J. , Minkara Mona S. , Wedler Hoby B. , Zechmann Bernd , Shaw Bryan F.
Published: January 2024

People with blindness have limited access to the high-resolution graphical data and imagery of science. Here, a lithophane codex is reported. Its pages display tactile and optical readouts for universal visualization of data by persons with or without eyesight. Prototype codices illustrated microscopy of butterfly chitin—from
N
-acetylglucosamine monomer to fibril, scale, and whole insect—and were given to high schoolers from the Texas School for the Blind and Visually Impaired. Lithophane graphics of Fischer-Spier esterification reactions and electron micrographs of biological cells were also 3D-printed, along with x-ray structures of proteins (as millimeter-scale 3D models). Students with blindness could visualize (describe, recall, distinguish) these systems—for the first time—at the same resolution as sighted peers (average accuracy = 88%). Tactile visualization occurred alongside laboratory training, synthesis, and mentoring by chemists with blindness, resulting in increased student interest and sense of belonging in science.
Undepleted direct laser acceleration
Authors: Cohen Itamar , Meir Talia , Tangtartharakul Kavin , Perelmutter Lior , Elkind Michal , Gershuni Yonatan , Levanon Assaf , Arefiev Alexey V. , Pomerantz Ishay
Published: January 2024

Intense lasers enable generating high-energy particle beams in university-scale laboratories. With the direct laser acceleration (DLA) method, the leading part of the laser pulse ionizes the target material and forms a positively charged ion plasma channel into which electrons are injected and accelerated. The high energy conversion efficiency of DLA makes it ideal for generating large numbers of photonuclear reactions. In this work, we reveal that, for efficient DLA to prevail, a target material of sufficiently high atomic number is required to maintain the injection of ionization electrons at the peak intensity of the pulse when the DLA channel is already formed. We demonstrate experimentally and numerically that, when the atomic number is too low, the target is depleted of its ionization electrons prematurely. Applying this understanding to multi-petawatt laser experiments is expected to result in increased neutron yields, a perquisite for a wide range of research and applications.
Lasing of moiré trapped MoSe
2
/WSe
2
interlayer excitons coupled to a nanocavity
Authors: Qian Chenjiang , Troue Mirco , Figueiredo Johannes , Soubelet Pedro , Villafañe Viviana , Beierlein Johannes , Klembt Sebastian , Stier Andreas V. , Höfling Sven , Holleitner Alexander W. , Finley Jonathan J.
Published: January 2024

We report lasing of moiré trapped interlayer excitons (IXs) by integrating a pristine hBN-encapsulated MoSe
2
/WSe
2
heterobilayer into a high-
Q
(>10
4
) nanophotonic cavity. We control the cavity-IX detuning using a magnetic field and measure their dipolar coupling strength to be 78 ± 4 micro–electron volts, fully consistent with the 82 micro–electron volts predicted by theory. The emission from the cavity mode shows clear threshold-like behavior as the transition is tuned into resonance with the cavity. We observe a superlinear power dependence accompanied by a narrowing of the linewidth as the distinct features of lasing. The onset and prominence of these threshold-like behaviors are pronounced at resonance while weak off-resonance. Our results show that a lasing transition can be induced in interacting moiré IXs with macroscopic coherence extending over the length scale of the cavity mode. Such systems raise interesting perspectives for low-power switching and synaptic nanophotonic devices using two-dimensional materials.
Quantum control of flying doughnut terahertz pulses
Authors: Jana Kamalesh , Mi Yonghao , Møller Søren H. , Ko Dong Hyuk , Gholam-Mirzaei Shima , Abdollahpour Daryoush , Sederberg Shawn , Corkum Paul B.
Published: January 2024

The ability to manipulate the multiple properties of light diversifies light-matter interaction and light-driven applications. Here, using quantum control, we introduce an approach that enables the amplitude, sign, and even configuration of the generated light fields to be manipulated in an all-optical manner. Following this approach, we demonstrate the generation of “flying doughnut” terahertz (THz) pulses. We show that the single-cycle THz pulse radiated from the dynamic ring current has an electric field structure that is azimuthally polarized and that the space- and time-resolved magnetic field has a strong, isolated longitudinal component. We apply the flying doughnut pulse for a spectroscopic measurement of the water vapor in ambient air. Pulses such as these will serve as unique probes for spectroscopy, imaging, telecommunications, and magnetic materials.
Allele-specific control of rodent and human lncRNA KMT2E-AS1 promotes hypoxic endothelial pathology in pulmonary hypertension
Authors: Tai Yi-Yin , Yu Qiujun , Tang Ying , Sun Wei , Kelly Neil J. , Okawa Satoshi , Zhao Jingsi , Schwantes-An Tae-Hwi , Lacoux Caroline , Torrino Stephanie , Al Aaraj Yassmin , El Khoury Wadih , Negi Vinny , Liu Mingjun , Corey Catherine G. , Belmonte Frances , Vargas Sara O. , Schwartz Brian , Bhat Bal , Chau B. Nelson , Karnes Jason H. , Satoh Taijyu , Barndt Robert J. , Wu Haodi , Parikh Victoria N. , Wang Jianrong , Zhang Yingze , McNamara Dennis , Li Gang , Speyer Gil , Wang Bing , Shiva Sruti , Kaufman Brett , Kim Seungchan , Gomez Delphine , Mari Bernard , Cho Michael H. , Boueiz Adel , Pauciulo Michael W. , Southgate Laura , Trembath Richard C. , Sitbon Olivier , Humbert Marc , Graf Stefan , Morrell Nicholas W. , Rhodes Christopher J. , Wilkins Martin R. , Nouraie Mehdi , Nichols William C. , Desai Ankit A. , Bertero Thomas , Chan Stephen Y.
Published: January 2024

Hypoxic reprogramming of vasculature relies on genetic, epigenetic, and metabolic circuitry, but the control points are unknown. In pulmonary arterial hypertension (PAH), a disease driven by hypoxia inducible factor (HIF)–dependent vascular dysfunction, HIF-2α promoted expression of neighboring genes, long noncoding RNA (lncRNA) histone lysine
N
-methyltransferase 2E-antisense 1 (
KMT2E-AS1
) and histone lysine N-methyltransferase 2E (
KMT2E
).
KMT2E-AS1
stabilized KMT2E protein to increase epigenetic histone 3 lysine 4 trimethylation (H3K4me3), driving HIF-2α–dependent metabolic and pathogenic endothelial activity. This lncRNA axis also increased HIF-2α expression across epigenetic, transcriptional, and posttranscriptional contexts, thus promoting a positive feedback loop to further augment HIF-2α activity. We identified a genetic association between rs73184087, a single-nucleotide variant (SNV) within a
KMT2E
intron, and disease risk in PAH discovery and replication patient cohorts and in a global meta-analysis. This SNV displayed allele (G)–specific association with HIF-2α, engaged in long-range chromatin interactions, and induced the lncRNA-KMT2E tandem in hypoxic (G/G) cells. In vivo,
KMT2E-AS1
deficiency protected against PAH in mice, as did pharmacologic inhibition of histone methylation in rats. Conversely, forced lncRNA expression promoted more severe PH. Thus, the
KMT2E-AS1
/KMT2E pair orchestrates across convergent multi-ome landscapes to mediate HIF-2α pathobiology and represents a key clinical target in pulmonary hypertension.
CD8 cis-targeted IL-2 drives potent antiviral activity against hepatitis B virus
Authors: Andreata Francesco , Moynihan Kelly D. , Fumagalli Valeria , Di Lucia Pietro , Pappas Danielle C. , Kawashima Keigo , Ni Irene , Bessette Paul H. , Perucchini Chiara , Bono Elisa , Giustini Leonardo , Nguyen Henry C. , Chin S. Michael , Yeung Yik Andy , Gibbs Craig S. , Djuretic Ivana , Iannacone Matteo
Published: January 2024

CD8
+
T cells are key antiviral effectors against hepatitis B virus (HBV), yet their number and function can be compromised in chronic infections. Preclinical HBV models displaying CD8
+
T cell dysfunction showed that interleukin-2 (IL-2)–based treatment, unlike programmed cell death ligand 1 (PD-L1) checkpoint blockade, could reverse this defect, suggesting its therapeutic potential against HBV. However, IL-2’s effectiveness is hindered by its pleiotropic nature, because its receptor is found on various immune cells, including regulatory T (T
reg
) cells and natural killer (NK) cells, which can counteract antiviral responses or contribute to toxicity, respectively. To address this, we developed a cis-targeted CD8-IL2 fusion protein, aiming to selectively stimulate dysfunctional CD8
+
T cells in chronic HBV. In a mouse model, CD8-IL2 boosted the number of HBV-reactive CD8
+
T cells in the liver without substantially altering T
reg
or NK cell counts. These expanded CD8
+
T cells exhibited increased interferon-γ and granzyme B production, demonstrating enhanced functionality. CD8-IL2 treatment resulted in substantial antiviral effects, evidenced by marked reductions in viremia and antigenemia and HBV core antigen–positive hepatocytes. In contrast, an untargeted CTRL-IL2 led to predominant NK cell expansion, minimal CD8
+
T cell expansion, negligible changes in effector molecules, and minimal antiviral activity. Human CD8-IL2 trials in cynomolgus monkeys mirrored these results, achieving a roughly 20-fold increase in peripheral blood CD8
+
T cells without affecting NK or T
reg
cell numbers. These data support the development of CD8-IL2 as a therapy for chronic HBV infection.
Ceramide promotes lytic reactivation of Epstein-Barr virus in gastric carcinoma
Authors: Kim Jun Yeob , Min Young Jin , Lee Min-Hyeok , An Yea Rim , Ashktorab Hassan , Smoot Duane T. , Kwon Sung Won , Lee Suk Kyeong
Published: January 2024

Epstein-Barr virus remains dormant in the host cell but occasionally switches to the lytic cycle when stimulated. However, the exact molecular mechanism of this lytic induction is not well understood. In this study, we demonstrate that Epstein-Barr virus infection leads to a reduction in ceramide levels. Additionally, the restoration of ceramide levels triggers lytic replication of Epstein-Barr virus with increase in phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and CREB. Our study suggests that the Epstein-Barr virus can inhibit lytic replication and remain latent through reduction of host cell ceramide levels. This study reports the regulation of lytic replication by ceramide in Epstein-Barr virus-positive gastric cancer.
Preliminary evidence for chaotic signatures in host-microbe interactions
Authors: Sella Yehonatan , Broderick Nichole A. , Stouffer Kaitlin M. , McEwan Deborah L. , Ausubel Frederick M. , Casadevall Arturo , Bergman Aviv
Published: January 2024

Is microbial pathogenesis a predictable scientific field? At a time when we are dealing with coronavirus disease 2019, there is intense interest in knowing about the epidemic potential of other microbial threats and new emerging infectious diseases. To know whether microbial pathogenesis will ever be a predictable scientific field requires knowing whether a host-microbe interaction follows deterministic, stochastic, or chaotic dynamics. If randomness and chaos are absent from virulence, there is hope for prediction in the future regarding the outcome of microbe-host interactions. Chaotic systems are inherently unpredictable, although it is possible to generate short-term probabilistic models, as is done in applications of stochastic processes and machine learning to weather forecasting. Information on the dynamics of a system is also essential for understanding the reproducibility of experiments, a topic of great concern in the biological sciences. Our study finds preliminary evidence for chaotic dynamics in infectious diseases.
Agony of akathisia: a case of sodium valproate-induced akathisia
Authors: Lim Gareth , Tang Aaron , Wing Tracey , Lai Jonathan
Published: January 2024

Akathisia is a subjective feeling of restlessness that often results in a compulsion to move. Drug-related causes are the most common aetiologies. It can often be confused with restless legs syndrome (RLS). We describe a case of valproate-induced akathisia that improved with drug cessation. This case reports a rare but treatable adverse effect of sodium valproate and highlights the importance of differentiating akathisia from RLS.
Intravenous lipid emulsion for a life-threatening prothipendyl intoxication
Authors: Meunier Anne , Goffin Pierre , Deville Marine , Demaret Pierre
Published: January 2024

Prothipendyl, a lipophilic neuroleptic drug, requires a careful dosage regimen due to its potential side effects, including life-threatening arrhythmias.

This report outlines a case of severe prothipendyl intoxication, its management and the successful utilisation of Intralipid, an intravenous lipid emulsion, in treating ventricular arrhythmia postmassive prothipendyl ingestion. Additionally, the mechanism of action of Intralipid and the rebound concentration of the lipophilic drug in such scenarios are discussed.
Detection of methaemoglobinaemia in a COVID-19 patient on dapsone
Authors: Chagani Fatima , Bansari Asha , Dass Bhagwan
Published: January 2024

Methaemoglobinaemia occurs when iron in haemoglobin is oxidised into a form that cannot transport oxygen. At low levels, it is asymptomatic, though at rising levels symptoms arise from impaired oxygenation, and it can ultimately be fatal. While uncommon, it is important to consider in hypoxaemic COVID-19 patients, especially if they are not clinically improving on standard treatments and workup for other causes does not explain the ongoing hypoxaemia. It is often diagnosed through a mismatch in peripheral and arterial oxygen, with the former typically less than the latter. We present the case of a COVID-19 patient who was found to have methaemoglobinaemia due to dapsone use for Pneumocystic jirovecii pneumonia (PJP) prophylaxis while on chemotherapy. Dapsone was stopped and supplemental high-flow nasal cannula was provided, and methaemoglobin levels improved over a 5-day period. She was discharged to follow-up with her haematologist in the clinic.
Myeloblastic meningeal neoplasm: an unusual natural history
Authors: Gomathy Saranya B , Kakkar Aanchal , Gupta Ritu , Elavarasi Arunmozhimaran
Published: January 2024

Myeloid sarcoma is a very rare extramedullary malignant tumour, most often associated with acute myeloid leukaemia. We report the case of a man in his early 20s who presented with chronic headache, raised intracranial pressure and progressive vision loss of 2 years duration with no systemic manifestations. He had a history of myeloid sarcoma of the left thigh 15 years ago, treated with external beam radiotherapy and in complete remission for more than 13 years. However, the progressive blindness remained unexplained for 2 years, and he was eventually diagnosed with isolated meningeal relapse without marrow or systemic involvement. Imaging revealed subarachnoid haemorrhage, diffuse leptomeningeal enhancement and involvement of lower dorsal cord and conus, and cerebrospinal fluid cytology showed myeloid blasts. He was managed with intrathecal chemotherapy and craniospinal irradiation, after which he had mild improvement in vision.
Obsessive-compulsive disorder following severe traumatic brain injury
Authors: Wilson Alison Janelle , King Regan , Debert Chantel
Published: January 2024

Obsessive-compulsive disorder (OCD) as a consequence of severe traumatic brain injury (TBI) has been reported in a limited number of case studies. Informed by CARE guidelines, we present the case of a boy in his late adolescence who sustained a severe TBI from a motor vehicle crash. His injuries required a prolonged stay in the hospital, including 3 weeks in the intensive care unit and a craniotomy to evacuate a large subdural haematoma. Obsessive-compulsive behaviours were first observed on discharge from the hospital and became worse over time. Compulsive behaviours were considered in light of a neuropsychological examination, and a diagnosis of OCD was attained. Sertraline was prescribed and effectively reduced the severity of OCD symptoms. Given the challenges comorbid conditions can pose to neurorehabilitation, a better understanding of patterns in OCD symptoms and brain lesions among reported cases will help guide the diagnosis of OCD among individuals with severe TBI.
Familial visceral branch artery aneurysms in Loeys-Dietz syndrome
Authors: Lim Michelle S , Steinbrecher Kacie , Koefoed Andrew W , Braverman Alan C
Published: January 2024

Loeys-Dietz syndrome (LDS) is an autosomal dominant heritable disorder due to pathogenic variants in one of several genes involved in TGF-β (transforming growth factor-beta) signalling. LDS is associated with aortic aneurysm and dissection. LDS may also lead to extra-aortic aneurysms, the majority of which occur in the head and neck vasculature. Visceral aneurysms are uncommon, and no cases of distal superior mesenteric artery (SMA) branch aneurysms in patients with LDS have been reported. Three related females withTGFBR1-related LDS developed distal SMA branch artery aneurysms involving the ileocolic and jejunal arteries. Endovascular or surgical intervention was performed in each. The presence and severity of arterial, craniofacial, and cutaneous features of LDS in these patients are variable.TGFBR1-related LDS may rarely lead to SMA branch artery aneurysms that can develop later in life. Surgical and endovascular procedures can successfully treat these aneurysms, but data to guide size thresholds and optimal treatment strategies are lacking.
Pericardial actinomycosis
Authors: Paterson Georgia E , Dickens Felicity J , Hurdman Judith A , Pirzada Omar M
Published: January 2024

A man in his 50s, with a history of night sweats and weight loss, presented acutely with dyspnoea and chest pain. Imaging revealed right middle lobe consolidation and a large pericardial effusion. The diagnosis of actinomycosis was made using endobronchial ultrasound-guided sampling from the pericardial effusion. An orthopantomogram demonstrated that the source was a large cavity in the left lower wisdom tooth. This tooth was extracted before the completion of his antibiotic course, and the patient made a full recovery. Cardiac actinomycosis is rare, and there are few case reports describing endobronchial ultrasound-guided sampling of pericardial fluid.
Acute fracture of an extensively ossified segment of the Achilles tendon
Authors: Hillman Charles , Mangwani Jitendra , Kluzek Stefan
Published: January 2024

Extensive tendon ossification is thought to be rare and is hypothesised to occur due to cell-mediated tissue remodelling. Literature outlining risk factors for the development of an ossified segment, and then a consequent fracture is limited to case reports and case series. A woman in her fifties with a background of several autoimmune disorders presented to a sports and exercise medicine clinic with posterior ankle pain following a bout of brisk walking a month prior. CT and MRI imaging demonstrated a fractured extensively ossified segment of the corresponding Achilles tendon. Conservative treatment was trialled for six months, however, was unsuccessful. Surgical excision of the calcified fragment and flexor hallucis longus tendon transfer were suggested as a potential solution. This case is compared with and builds on current literature surrounding pathophysiology and optimal treatment of extensively ossified segments of the Achilles tendon.
Spindly reason for a pulmonary embolism
Authors: Goldberg Alec , Chen Jason N , Breaux John , Pope Helen
Published: January 2024

Pulmonary artery intimal sarcomas (PAISs) are rare, malignant tumours that arise from the intimal or intramural wall of the pulmonary artery and are often mistaken for pulmonary emboli. Diagnosis and treatment of this condition are difficult due to the lack of formal guidelines. Initiating treatment as soon as possible after diagnosis is essential for maximising survival. Here, we present the case of a patient with a PAIS that initially presented similar to pulmonary thromboembolic disease and was treated with a multimodal approach.