bluuebunny/crossref_metadata_2025 huggingface dataset:
P.110 Evaluating AI performance in written neurosurgery exams: a comparative analysis of large language models
Authors: Guo E , Sanguinetti R , Ramchandani R , Lama S , Sutherland GR
Published: May 2024

Background: The integration of Artificial Intelligence (AI) in medical education is an area of growing importance. While AI models have been evaluated extensively in multiple-choice question formats, their proficiency in written exams remains to be explored. Methods: Four AI models—GPT-4 (OpenAI), Claude-2.1 (Anthropic), Gemini Pro (Google), and Perplexity 70B (Perplexity)—were tested using the Canadian Royal College Sample Neurosurgery Exam. The written exam covered diagnostic reasoning, knowledge of neurosurgical conditions, and understanding of radiographic imaging techniques. Results: GPT-4 and Perplexity 70B both achieved a score of 68.42%, followed by Claude-2.1 with 60.53%, and Gemini Pro with 57.89%. The models showed proficiency in answering questions that required factual knowledge, such as identifying pathogens in spinal epidural abscess. However, they struggled with more complex diagnostic reasoning tasks, particularly in explaining the pathophysiology behind a sudden rise in blood pressure during surgery and interpreting radiographic characteristics of intracranial abscesses on MRI. Conclusions: The findings indicate that while AI models like GPT-4 and Perplexity 70B are adept at handling factual neurosurgical questions, their performance in complex diagnostic reasoning in a written format is less consistent. This underscores the need for more advanced and specialized AI training, particularly in the nuances of medical diagnostics and decision-making.
P.124 Assessing the fragility index of randomized controlled trials on carotid artery stenosis: systematic review
Authors: Liu E , Tilbury N , Zhou A , Su J , Persad A , Newton B , Ahmed U , Peeling L , Kelly M
Published: May 2024

Background: The fragility index (FI) is the minimum number of patients whose status would have to change from a nonevent to an event to turn a statistically significant result to a non-significant result. We used this to measure the robustness of trials comparing carotid endarterectomy (CEA) to carotid artery stenting (CAS). Methods: A search was conducted in MEDLINE, Embase, and PubMed on RCTs comparing CEA to CAS. The trials need to have statistically significant results and dichotomous primary endpoints to be included. Results: Our literature search identified 10 RCTs which included 9382 patients (4734 CEA, 4648 CAS). The primary end points of all included trials favoured CEA over CAS. The median FI was 9.5 (interquartile range 2.25 - 21.25). All of the studies that reported lost-to-follow-up (LTFU) had LTFU greater than its fragility index, which raises concern that the missing data could change the results of the trial from statistically significant to statistically insignificant. Conclusions: A small number of events (FI, median 9.5) were required to render the results of carotid artery stenosis RCTs comparing CEA to CAS statistically insignificant. All of the studies that reported LTFU had LTFU greater than its fragility index.
P.126 An unlikely impersonator of primary brain tumours: Illustrative case report and literature review of primary angiitis of the central nervous system
Authors: Elder MW , Chornenka K , Marzoughi S , Hassanabad MF , Rizzuto MA
Published: May 2024

Background: Primary angiitis of the central nervous system (PACNS) is a rare inflammatory condition affecting the parenchymal and leptomeningeal vessels of the CNS. PACNS presenting as a solitary mass lesion (ML-PACNS) constitutes a rare subtype of this pathology. Herein we present the first case reported in Canada of ML-PACNS, presenting with clinical and radiographic findings consistent with a high grade glial neoplasm, as well as a review of the literature on ML-PACNS. Methods: Review of the literature from 1987-2023 was conducted using PubMed to identify features of ML-PACNS and possible treatment paradigms. Results: A number of case reports of ML-PACNS were identified, as well as 6 retrospective analyses of a total of 67 patients. Features such as faster rate of symptom onset, and investigations such as MRI vessel-wall imaging and MR spectroscopy were suggested for identification of ML-PACNS. Treatment was highly variable, but followed guidelines for other neuroinflammatory disorders. Conclusions: Preoperative differentiation between ML-PACNS and CNS neoplasms is difficult due to their similar clinical and radiographic features. However, making this distinction is crucial as PACNS mass lesions can regress entirely with immunosuppressive therapy, potentially obviating the requirement for surgical intervention. Beyond diagnostics, further research is required to establish and validate a treatment paradigm.
P.132 Blood loss quantification and management strategies in cranial neurosurgery: a systematic review
Authors: George DD , Chrisbacher J , Mattingly T , Schmidt T , Walter K
Published: May 2024

Background: Blood loss quantification and management are important facets of cranial surgery, having been linked with adverse outcomes if management is inadequate. While many studies report estimated blood loss (EBL) as an outcome measure, inconsistencies exist in EBL quantification and management strategies Methods: A systematic review of cranial surgery literature on blood loss measurement and management was conducted according to PRISMA guidelines utilizing a novel software platform, Nested Knowledge Results: Initial search yielded 1029 non-duplicated. 107 full-text studies were included. 70% of studies were retrospective. Most common treatment conditions were 41% craniosynostosis (44/107) and 36% tumor (39/107). Most common EBL measurement methods were comparison of pre-operative and post-operative hemoglobin/hematocrit in 46.7% (50/107), anesthesia record in 26.2% (28/107), and surgeon estimation in 9.3% (10/107). 53.3% of studies did not specify a quantification methodology. Blood loss management strategies also varied, with transfusion being the most common method in 64.5% (69/107) of studies Conclusions: EBL quantification and blood loss management remain important clinical and research metrics. Despite this, significant heterogeneity exists in blood loss quantification and management strategies, with most studies providing no data on EBL quantification. Standardization of EBL quantification/reporting should be undertaken to improve comparability and consistency across studies.
P.147 The growing problem of spine surgery wait times in British Columbia: longitudinal trends and impacts on perioperative outcomes
Authors: Wang JC , Dea N , Charest-Morin R , Fisher C , Dvorak M , Kwon B , Ailon T , Paquette S , Street J , Dandurand C
Published: May 2024

Background: Surgical delays are in common in Canada. Wait times in elective spine surgery and their impact on outcomes remain uncharacterized. Methods: This was a single-center analysis of elective spine surgery data between 2009-2020. Wait times between referral and consultation (T1), consultation and surgical booking (Ti), and booking and surgery (T2) were assessed. Results: 2041 patients were included. Longitudinal analyses were adjusted for age, sex, diagnosis, surgical volume, while outcomes analyses were age and sex-adjusted. Total T1+Ti+T2 increased 8.1% annually (p<0.001). T1 decreased 4.3% annually (p=0.032). It was not associated with adverse events (AEs) or disposition. Every 100 days of T1 was associated with 1.0% longer hospitalization (p=0.001). Ti increased 21.0% annually (p<0.001). Every 100 days of Ti was associated with 2.9% increased odds of an adverse event (p=0.002), 1.8% longer hospitalization (p<0.001), and 15.9% increased likelihood of discharge home (p<0.001). T2 increased 7.0% annually (p<0.001) and was not associated with AEs. Every 100 days of T2 was associated with 11.6% longer hospitalization (p<0.001) and 76.5% increased likelihood of discharge home (p<0.001). Conclusions: Total wait times for elective spine surgery have increased between 2009-2020. Notably, Ti increased ninefold and was associated with AEs. This study highlights areas of delay and targets for healthcare optimization.
B.4 Stroke care and neurological emergency response simulation (SCaNERS): high-fidelity acute stroke simulation and its impact on knowledge retention
Authors: Daud Shah B , Graham B
Published: May 2024

Background: Stroke simulation-based training has been associated with improved stroke quality metrics. The purpose of this study was to assess whether high-fidelity acute stroke simulation participation led to better knowledge retention one month post simulation in off-service residents. Methods: Off-service residents were provided with non-mandatory pre-simulation pre-reading on stroke. Immediately before stroke simulation, they completed a questionnaire to test their knowledge on a set of 8 questions related to stroke. Immediately post-stroke simulation, they were provided with a debrief including teaching on stroke. After the debrief and one month later, they completed the same questionnaire again. Results: There were a total of 16 off-service resident participants. Wilcoxon signed ranks test was performed. There was a significant difference between pre-simulation and immediate post-simulation scores on the knowledge retention questionnaire (p = 0.008). There was a significant difference between pre-simulation and one-month post-simulation on the knowledge retention questionnaire (p = 0.007). There was no difference between immediate post-simulation and one-month post-simulation on the knowledge retention questionnaire (p = 0.77). Conclusions: Participants performed better on the questionnaire after the simulation, and this improved performance was retained at one month. This is the first study to demonstrate delayed knowledge retention in stroke simulation literature.
C.6 Sex differences in neurodevelopmental outcomes and brain development from early-life to 8-years in preterm males and females
Authors: Christensen R , Chau V , Synnes A , Guo T , Grunau R , Miller S
Published: May 2024

Background: Sex is associated with differences in early outcomes with preterm males at greater risk for mortality and morbidity. The objective of this study was to examine preterm sex differences in neurodevelopmental outcomes and brain development from early-life to 8-years. Methods: A prospective cohort of preterm infants born 24-32 weeks gestation were followed to 8-years with standardized measures. MRI scans were performed after birth, term-equivalent age and 8-years. Associations between sex, risk factors, brain volumes, white matter fractional anisotropy (FA) and outcomes were assessed using generalized estimating equations. Results: Preterm males (N=83) and females (N=72) had similar risk factors, brain injury and pain exposure. Sex was a predictor of cognitive scores (P=0.02) and motor impairment (P=0.03), with males having lower cognitive scores and higher motor impairment over time. There was a sex effect for FA (P=0.04), with males having lower FA over time. There were significant sex-brain injury and sex-pain interactions for cognitive and motor outcomes. Conclusions: In this longitudinal study, preterm males had lower cognitive scores and greater motor impairment, which may relate to differences in white matter maturation. Effects of brain injury and pain on outcomes is moderated by sex, indicating a differential response to early-life adversity in preterm males and females.
Coupled bulk and interfacial transport of surfactants governs the settling of a drop towards a wall
Authors: Jadhav Sayali N. , Mandal Shubhadeep , Ghosh Uddipta
Published: May 2024

Surfactant-like impurities are omnipresent in multiphase emulsions and may substantially affect the motion of small droplets by altering their interfacial properties. Usually these surfactants are soluble in the bulk and undergo adsorption–desorption onto the interface which modifies their surface concentration and hence their overall influence on droplet motion. Yet, the impact of the bulk solubility and transport of surfactants on droplet dynamics, especially in the presence of bounding walls, remains poorly understood. As such, in this article, we assess the impact of bulk soluble surfactants on the settling of a spherical drop towards a plane wall. We consider coupled bulk and interfacial transport of surfactants, mediated by adsorption–desorption processes and construct a semi-analytical framework for arbitrary values of ‘bulk interaction parameter’, which dictates the strength of adsorption–desorption kinetics compared with bulk diffusion. Our results indicate that while mass exchange between the bulk and the interface can remobilize the drop, a finite bulk diffusion rate restricts this process and therefore slows down the drop. This also results in bulk concentration depletion near the south pole and accumulation near the north pole, the extent of which becomes strongly asymmetric with an enhanced intensity of depletion, as the drop approaches the wall. Presence of the wall and bulk solubility are found to aid each other towards remobilizing the drop by aptly modifying the interfacial concentration. Our results may provide fundamental insights into the kinetics of surfactant-laden drops, with potential applications in food and pharmaceutical industries, separation processes, etc.
EHMMQA: English, Hindi, and Marathi multilingual question answering framework using deep learning
Authors: Lahoti Pawan , Mittal Namita , Singh Girdhari
Published: May 2024

Multilingual question answering (MQA) is an effective access to multilingual data to provide accurate and precise answers, irrespective of language. Although a wide range of datasets is available for monolingual QA systems in natural language processing, benchmark datasets specifically designed for MQA are considerably limited. The absence of comprehensive and benchmark datasets hinders the development and evaluation of MQA systems. To overcome this issue, the proposed work attempts to develop the EHMQuAD dataset, an MQA dataset for low-resource languages such as Hindi and Marathi accompanying the English language. The EHMQuAD dataset is developed using a synthetic corpora generation approach, and an alignment is performed after translation to make the dataset more accurate. Further, the EHMMQA model is proposed to create an abstract framework that uses a deep neural network that accepts pairs of questions and context and returns an accurate answer based on those questions. The shared question and shared context representation have been designed separately to develop this system. The experiments of the proposed model are conducted on the MMQA, Translated SQuAD, XQuAD, MLQA, and EHMQuAD datasets, and EM and F1-score are used as performance measures. The proposed model (EHMMQA) is collated with state-of-the-art MQA baseline models for all possible monolingual and multilingual settings. The results signify that EHMMQA is a considerable step toward the MQA system utilizing Hindi and Marathi languages. Hence, it becomes a new state-of-the-art model for Hindi and Marathi languages.
AI approaches for the discovery and validation of drug targets
Authors: Wenteler Aaron , Cabrera Claudia P. , Wei Wei , Neduva Victor , Barnes Michael R.
Published: May 2024

Artificial intelligence (AI) holds immense promise for accelerating and improving all aspects of drug discovery, not least target discovery and validation. By integrating a diverse range of biological data modalities, AI enables the accurate prediction of drug target properties, ultimately illuminating biological mechanisms of disease and guiding drug discovery strategies. Despite the indisputable potential of AI in drug target discovery, there are many challenges and obstacles yet to be overcome, including dealing with data biases, model interpretability and generalisability, and the validation of predicted drug targets, to name a few. By exploring recent advancements in AI, this review showcases current applications of AI for drug target discovery and offers perspectives on the future of AI for the discovery and validation of drug targets, paving the way for the generation of novel and safer pharmaceuticals.
Colonial Business in Postcolonial Germany: The Imperial Afterlives of C. Woermann, 1919–1945
Authors: Todzi Kim Sebastian
Published: May 2024

Situating itself at the intersection of colonial history, global history and business history, this article highlights the overlooked history of German colonial companies post-First World War. It argues for an ‘imperial afterlife’ through continued German corporate interests in African markets, emphasising the economic dimension of imperialism. Using C. Woermann as an example, it shows how the company adapted to the post-First World War global order, underwent organisational changes, and merged with National Socialist policies in Eastern Europe after 1939, revealing the adaptability of imperial enterprises.
Multiple recurrent supraventricular tachycardia in infantile tuberous sclerosis complex: management requiring triple-drug therapy
Authors: Jacquemyn Xander , Kutty Shelby , Cohen Mitchell I. , Mehta Keyur K.
Published: May 2024

We report the case of a female neonate admitted to the neonatal ICU with a rapid, narrow-complex tachyarrhythmia determined to be supraventricular tachycardia. Multimodality imaging and genetic testing confirmed a diagnosis of tuberous sclerosis complex with multiple cardiac rhabdomyomas. At 13 days of age, the patient was readmitted, exhibiting recurrent supraventricular tachycardia non-responsive to first-line treatment. Management required triple-drug therapy, whereafter the patient remained stable without recurrences. This is a rare report of supraventricular tachycardia in a functionally normal heart with the occurrence of supraventricular tachycardia due to structural abnormalities, with the possibility of multiple concealed accessory pathways.
Factors associated with renal oxygen extraction in mechanically ventilated children after the Norwood operation: insights from high fidelity haemodynamic data
Authors: Loomba Rohit S. , Villarreal Enrique G. , Farias Juan S. , Flores Saul , Wong Joshua
Published: May 2024

Background:

Maintaining the adequacy of systemic oxygen delivery is of utmost importance, particularly in critically ill children. Renal oxygen extraction can be utilised as metric of the balance between systemic oxygen delivery and oxygen consumption. The primary aim of this study was to determine what clinical factors are associated with renal oxygen extraction in children after Norwood procedure.

Methods:

Mechanically ventilated children who underwent Norwood procedure from 1 September, 2022 to 1 March, 2023 were identified as these patients had data collected and stored with high fidelity by the T3 software. Data regarding haemodynamic values, fluid balance, and airway pressure were collected and analysed using Bayesian regression to determine the association of the individual metrics with renal oxygen extraction.

Results:

A total of 27,270 datapoints were included in the final analyses. The resulting top two models explained had nearly 80% probability of being true and explained over 90% of the variance in renal oxygen extraction. The coefficients for each variable retained in the best were −1.70 for milrinone, −19.05 for epinephrine, 0.129 for mean airway pressure, −0.063 for mean arterial pressure, 0.111 for central venous pressure, 0.093 for arterial saturation, 0.006 for heart rate, −0.025 for respiratory rate, 0.366 for systemic vascular resistance, and −0.032 for systemic blood flow.

Conclusion:

Increased milrinone, epinephrine, mean arterial pressure, and systemic blood flow were associated with decreased (improved) renal oxygen extraction, while increased mean airway pressure, central venous pressure, arterial saturation, and systemic vascular resistance were associated with increased (worsened) renal oxygen extraction.
Transforming the Rule of Law in Environmental and Climate Litigation: Prohibiting the Arbitrary Treatment of Future Generations
Authors: Sulyok Katalin
Published: May 2024

This article maps the shared legal anatomy of climate and environmental lawsuits, in which plaintiffs claim protection for future generations before domestic or international courts. By closely analyzing the litigation strategies of plaintiffs and the inquiry of courts, the article argues that these proceedings revolve around structurally similar legal standards across domestic and international jurisdictions, which correspond to five normative requirements flowing from the rule of law: namely, respect for human rights, certain quality of law requirements, prohibition of arbitrary exercise of governmental powers, non-discrimination, and access to justice. The cross-jurisdictional analysis shows that courts appear to be increasingly willing to protect future generations against arbitrary treatment by present-day decision makers. The article appraises whether such an intergenerationally sensitive reinterpretation of the rule of law could help to change the short-termist paradigm of environmental and climate law.
Distributed Optical Fibre Sensing for High Space‐Time Resolution Ocean Velocity Observations: A Case Study From a Macrotidal Channel
Authors: Spingys Carl P. , Naveira Garabato Alberto C. , Belal Mohammad
Published: May 2024

Despite significant recent technological advances, oceanographic observations on horizontal scales of meters to a few kilometres prove challenging. Exploiting legacy seafloor cables presents a disruptive prospect to address this gap, as it may provide low‐cost sustained observations with high space‐time resolution, enabled through novel opto‐electronic interrogation of optical fibers within the cables. Here, we demonstrate this approach in a renewable tidal energy cable embedded within a region with a strong barotropic tide. By making remote measurements continuously over 12 hr, we obtain the distributed differential strain experienced by 2 km of offshore cable from a diverse range of oceanic flow processes, with an along‐cable resolution of 2.04 m. We successfully identify: (a) nearshore wave breaking and its modulation by changes in water depth; (b) along‐cable tidal velocity, shown to be linearly related to the differential strain; and (c) high‐frequency motions consistent with 3‐dimensional turbulent processes, either of natural origin or from flow‐cable interaction. These inferences are supported by nearby conventional measurements of water depth and velocity.
Is Bias Correction in Dynamical Downscaling Defensible?
Authors: Risser Mark D. , Rahimi Stefan , Goldenson Naomi , Hall Alex , Lebo Zachary J. , Feldman Daniel R.
Published: May 2024

Localized projections of 21st‐century hydroclimate variables obtained from downscaling Global Climate Model (GCM) output are central to informing regional impact assessments and infrastructure planning. Regional GCM biases can be significant and, for dynamical downscaling, can be addressed either before (a priori) or after (a posteriori) downscaling. However, a priori bias correction (APBC) has generally unexplored effects on climate change signals. Here we analyze dynamically downscaled solutions of CMIP6 GCMs over the Western U.S., with and without APBC, and quantify APBC's impact on climate change signals relative to other irreducible uncertainty sources. For temperature and precipitation, the uncertainty introduced by APBC is negligible compared to that arising from GCM choice or internal variability. Furthermore, APBC greatly reduces regional models' unrealistically high snow‐water‐equivalent (SWE) biases that result directly from GCM errors. We leverage this finding to encourage the dynamical downscaling community to adopt APBC as a standard operating procedure.
A Living Assessment of Different Materials for Stratospheric Aerosol Injection—Building Bridges Between Model World and the Messiness of Reality
Authors: Visioni Daniele , Quaglia Ilaria , Steinke Isabelle
Published: May 2024

There are obstacles in better understanding the climate impacts associated with new materials that could be used for Stratospheric Aerosol Injections (SAI), like the lack of an integrated framework that combines climate modeling across scales, laboratory studies and small‐scale field experiments. Vattioni et al. (2023, https://doi.org/10.1029/2023gl105889) explored one aspect of using alternative, non‐sulfate materials for SAI. They investigated how uncertain the response of stratospheric ozone would be to alumina injections for SAI. In their study, they quantify chlorine activation rates in the presence of alumina, and then cascade these uncertainties into estimates of ozone depletion, concluding that alumina might have less detrimental impacts on stratospheric chemistry than sulfate, but with large uncertainties. Their results provide a useful basis upon which future research endeavors combining indoor and outdoor experiments and modeling may be structured to produce robust assessments of SAI impacts, benefits and uncertainties, together with clarifying what kind of research needs to be prioritized.
Cloud Radiative Effects Associated With Daily Weather Regimes
Authors: Zhao Ming
Published: May 2024

Using high temporal resolution satellite observations and reanalysis data, we classify daily weather into distinct regimes and quantify their associated cloud radiative effect (CRE) to better understand the roles of various weather systems in affecting Earth's top‐of‐atmosphere radiation budget. These regimes include non‐precipitation, drizzle, wet non‐storm, and storm days, which encompass atmospheric rivers (AR), tropical storms (TS), and mesoscale convection systems (MCS). We find that precipitation (wet) days account for roughly 80% (60%) of global longwave (LW) and shortwave (SW) CREs due to their large frequency and high intensity in CRE. Despite being rare globally (13%), AR, TS, and MCS days together account for 32% of global LW CRE and 27% of SW CRE due to their higher intensity in LW and SW CRE. These results enhance our understanding of how various weather systems, particularly severe storms, influence Earth's radiative balance, and will help to better constrain climate models.
Visualization of cristae and mtDNA interactions via STED nanoscopy using a low saturation power probe
Authors: Ren Wei , Ge Xichuan , Li Meiqi , Sun Jing , Li Shiyi , Gao Shu , Shan Chunyan , Gao Baoxiang , Xi Peng
Published: May 2024

Mitochondria are crucial organelles closely associated with cellular metabolism and function. Mitochondrial DNA (mtDNA) encodes a variety of transcripts and proteins essential for cellular function. However, the interaction between the inner membrane (IM) and mtDNA remains elusive due to the limitations in spatiotemporal resolution offered by conventional microscopy and the absence of suitable in vivo probes specifically targeting the IM. Here, we have developed a novel fluorescence probe called HBmito Crimson, characterized by exceptional photostability, fluorogenicity within lipid membranes, and low saturation power. We successfully achieved over 500 frames of low-power stimulated emission depletion microscopy (STED) imaging to visualize the IM dynamics, with a spatial resolution of 40 nm. By utilizing dual-color imaging of the IM and mtDNA, it has been uncovered that mtDNA tends to habitat at mitochondrial tips or branch points, exhibiting an overall spatially uniform distribution. Notably, the dynamics of mitochondria are intricately associated with the positioning of mtDNA, and fusion consistently occurs in close proximity to mtDNA to minimize pressure during cristae remodeling. In healthy cells, >66% of the mitochondria are Class III (i.e., mitochondria >5 μm or with >12 cristae), while it dropped to <18% in ferroptosis. Mitochondrial dynamics, orchestrated by cristae remodeling, foster the even distribution of mtDNA. Conversely, in conditions of apoptosis and ferroptosis where the cristae structure is compromised, mtDNA distribution becomes irregular. These findings, achieved with unprecedented spatiotemporal resolution, reveal the intricate interplay between cristae and mtDNA and provide insights into the driving forces behind mtDNA distribution.
Analysis of the acoustoelectric response of SAW gas sensors using a COM model
Authors: Yuan Yang , Yang Tao , Chen Xi , Yu Linglang , Hou Xiaoxiao , Zhang Guangzu , Dong Wen , Lu Zixiao , Li Honglang , Reindl Leonhard , Luo Wei
Published: May 2024

Surface acoustic wave (SAW) gas sensors based on the acoustoelectric effect exhibit wide application prospects for in situ gas detection. However, establishing accurate models for calculating the scattering parameters of SAW gas sensors remains a challenge. Here, we present a coupling of modes (COM) model that includes the acoustoelectric effect and specifically explains the nonmonotonic variation in the center frequency with respect to the sensing film’s sheet conductivity. Several sensing parameters of the gas sensors, including the center frequency, insertion loss, and phase, were experimentally compared for accuracy and practicality. Finally, the frequency of the phase extremum (FPE) shift was determined to vary monotonically, and the range of selectable test points was wide, making the FPE an appropriate response parameter for leveraging in SAW gas sensors. The simulation results of the COM model were highly consistent with the experimental results. Our study is proposed to provide theoretical guidance for the future development of gas SAW sensors.
Enhancing cellular behavior in repaired tissue via silk fibroin-integrated triboelectric nanogenerators
Authors: Li Zhelin , Xu Shuxing , Xu Zijie , Shu Sheng , Liu Guanlin , Zhou Jianda , Lin Ding , Tang Wei
Published: May 2024

Triboelectric nanogenerators (TENGs) have emerged as a promising approach for generating electricity and providing electrical stimuli in medical electronic devices. Despite their potential benefits, the clinical implementation of TENGs faces challenges such as skin compliance and a lack of comprehensive assessment regarding their biosafety and efficacy. Therefore, further research is imperative to overcome these limitations and unlock the full potential of TENGs in various biomedical applications. In this study, we present a flexible silk fibroin-based triboelectric nanogenerator (SFB-TENG) that features an on-skin substrate and is characterized by excellent skin compliance and air/water permeability. The range of electrical output generated by the SFB-TENG was shown to facilitate the migration and proliferation of Hy926, NIH-3T3 and RSC96 cells. However, apoptosis of fibroblast NIH-3T3 cells was observed when the output voltage increased to more than 20 V at a frequency of 2 Hz. In addition, the moderate electrical stimulation provided by the SFB-TENG promoted the cell proliferation cycle in Hy926 cells. This research highlights the efficacy of a TENG system featuring a flexible and skin-friendly design, as well as its safe operating conditions for use in biomedical applications. These findings position TENGs as highly promising candidates for practical applications in the field of tissue regeneration.
An automatic Q-factor matching method for eliminating 77% of the ZRO of a MEMS vibratory gyroscope in rate mode
Authors: Ren Jingbo , Zhou Tong , Zhou Yi , Li Yixuan , Su Yan
Published: May 2024

Mismatching quality factors (Q-factors) is one of the main factors causing zero-rate output (ZRO) in degenerate (DE) Micro-Electro-Mechanical Systems (MEMS) vibratory gyroscopes. To eliminate the ZRO of the DE MEMS gyroscope, this study introduces a method for real-time identification and automatic matching of Q-factors in rate mode. By leveraging the vibration characteristics of the DE MEMS vibratory gyroscope in rate mode, dedicated online test methods are designed to determine the Q-factors for both the drive and sense modes, enabling online identification of the Q-factor mismatching. Furthermore, an automatic Q-factor matching system is designed utilizing the mechanical-thermal dissipation mechanism of the resistive damper. The effectiveness of this proposed method is validated through simulations and experiments conducted on a MEMS disk resonator gyroscope (DRG). The results show a measurement error within 4% for Q-factor identification, and automatic Q-factor matching effectively reduces the ZRO by 77%. Employing this automatic Q-factor matching method successfully reduces the ZRO that is caused by the mismatching of Q-factors in the MEMS DRG from 0.11°/s to 0.025°/s and improves the bias instability (BI) from 0.40°/s to 0.19°/s.
Maintenance of peri-implant health in general dental practice
Authors: Perussolo ﻿Jeniffer , Donos Nikolaos
Published: May 2024

The long-term maintenance or restoration of peri-implant tissues‘ health depends on the strategic implementation of preventive measures and interventions. These measures should be initiated before implant placement and continued throughout a patient's lifetime, as part of a tailored and comprehensive supportive peri-implant care (SPIC) programme. Central to the clinical efforts of maintaining and rehabilitating peri-implant tissues are several key factors, including the ongoing assessment and frequent monitoring of tissue health and stability, proactive oral health promotion, the control of risk factors and indicators and the provision of professional plaque biofilm removal. It is of paramount importance to underline that SPIC should not limit its scope exclusively to patients already in a state of peri-implant health; in fact, it is imperative that it should extend its protective effect to individuals who have been previously diagnosed and treated for peri-implant diseases, focusing on preventing its recurrence and progression, thereby avoiding further complications, such as implant loss.

This narrative review presents an overview of the current literature on the maintenance of peri-implant tissues‘ health and the steps of SPIC providing insights into the critical factors to be considered when managing dental implant patients in the general dental practice.
Melatonin alleviates septic ARDS by inhibiting NCOA4-mediated ferritinophagy in alveolar macrophages
Authors: Xu Wenting , Wu Yutong , Wang Sheng , Hu Song , Wang Yu , Zhou Wenyu , Chen Yuanli , Li Quanfu , Zhu Lina , Yang Hao , Lv Xin
Published: May 2024

Ferroptosis is a novel form of programmed cell death which can exacerbate lung injury in septic acute respiratory distress syndrome (ARDS). Alveolar macrophages, crucial innate immune cells, play a pivotal role in the pathogenesis of ARDS. Ferritinophagy is a process of ferritin degradation mediated by nuclear receptor coactivator 4 (NCOA4) which releases large amounts of iron ions thus promoting ferroptosis. Recent evidence revealed that inhibiting macrophage ferroptosis can effectively attenuate pulmonary inflammatory injury. Melatonin (MT), an endogenous neurohormone, has antioxidant and anti-inflammatory effects and can reduce septic ARDS. However, it is not clear whether MT’s pulmonary protective effect is related to the inhibition of macrophage ferritinophagy. Our in vitro experiments demonstrated that MT decreased intracellular malondialdehyde (MDA), Fe2+, and lipid peroxidation levels, increased glutathione (GSH) levels and cell proliferation, and upregulated glutathione peroxidase 4 (GPX4) and ferritin heavy chain 1 (FTH1) protein levels in LPS-treated macrophages. Mechanistically, the antiferroptotic effect of MT on LPS-treated macrophages was significantly compromised by the overexpression of NCOA4. Our in vivo experiments revealed that MT alleviated the protein expression of NCOA4 and FTH1 in the alveolar macrophages of septic mice. Furthermore, MT improved lipid peroxidation and mitigated damage in alveolar macrophages and lung tissue, ultimately increasing the survival rates of septic mice. These findings indicate that MT can inhibit ferroptosis in an NCOA4-mediated ferritinophagy manner, thereby ameliorating septic ARDS.
PLCβ1 by-passes early growth response -1 to induce the differentiation of neuronal cells
Authors: González-Burguera Imanol , Lin Guanyu , López de Jesús Maider , Saumell-Esnaola Miquel , Barrondo Sergio , García del Caño Gontzal , Sallés Joan , Scarlata Suzanne
Published: May 2024

The Gαq/phospholipase C-β (PLCβ) signaling system mediates calcium responses to a variety of hormones and neurotransmitters. Recent studies suggest that PLCβ1 expression plays a role in the differentiation of two types of cultured neuronal cells (PC12 and SK-N-SH) through a mechanism independent of Gαq. Here, we show that, similar to that observed in PC12 and SK-N-SH cells, PLCβ1 expression increases when human NT2 cells are induced to differentiate either through cytosine-β-D-arabinofuranoside or retinoic acid. Preventing this increase, abolishes differentiation, and down-regulating PLCβ1 in rat primary astrocytes causes cells to adapt an undifferentiated morphology. Surprisingly, transfecting PLCβ1 into undifferentiated PC12 or NT2 cells induces differentiation without the need for differentiating agents. Studies to uncover the underlying mechanism focused on the transcription factor early growth response 1 (Egr-1) which mediates PLCβ1 expression early in differentiation. Over-expressing PLCβ1 in HEK293 cells enhances Egr-1 expression and induces morphological changes. We show that increased levels of cytosolic PLCβ1 in undifferentiated PC12 cells disrupts the association between Egr-1 and its cytosolic binding partner (Tar RNA binding protein), promoting relocalization of Egr-1 to the nucleus, which promotes transcription of proteins needed for differentiation. These studies show a novel mechanism through which differentiation can be modulated.
KDM5B promotes SMAD4 loss-driven drug resistance through activating DLG1/YAP to induce lipid accumulation in pancreatic ductal adenocarcinoma
Authors: Wang Yumin , Liu Shiqian , Wang Yan , Li Baibei , Liang Jiaming , Chen Yu , Tang Bo , Yu Shuiping , Wang Hongquan
Published: May 2024

Inactivated suppressor of mothers against decapentaplegic homolog (SMAD) 4 significantly affects cancer development in pancreatic ductal adenocarcinoma (PDAC). However, the contribution of smad4 loss to drug resistance in PDAC is largely undetermined. In the present study, we reported that the loss of SMAD4 endows PDAC cells the ability to drug resistance through upregulating histone lysine demethylase, Lysine-Specific Demethylase 5B (KDM5B, also known as JARID1B or PLU1). Upregulated KDM5B was found in PDAC, associated with poor prognosis and recurrence of PDAC patients. Upregulated KDM5B promotes PDAC tumor malignancy, i.e. cancer cells stemness and drug resistance in vitro and in vivo, while KDM5B knockout exerts opposite effects. Mechanistically, loss of Smad4-mediated upregulation of KDM5B promotes drug resistance through inhibiting the discs-large homolog 1 (DLG1), thereby facilitating nuclear translocation of YAP to induce de novo lipogenesis. Moreover, m6A demethylase FTO is involved in the upregulation of KDM5B by maintaining KDM5B mRNA stability. Collectively, the present study suggested FTO-mediated KDM5B stabilization in the context of loss of Smad4 activate DLG1/YAP1 pathway to promote tumorigenesis by reprogramming lipid accumulation in PDAC. Our study confirmed that the KDM5B-DLG1-YAP1 pathway axis plays a crucial role in the genesis and progression of PDAC, and KDM5B was expected to become a target for the treatment of PDAC.
Mutant kri1l causes abnormal retinal development via cell cycle arrest and apoptosis induction
Authors: Zhang Rong , Sun Jiajun , Xie Yabin , Zhu Wei , Tao Meitong , Chen Yu , Xie Wei , Bade Rengui , Jiang Shuyuan , Liu Xiaolei , Shao Guo , Pan Weijun , Zhou Chengjiang , Jia Xiaoe
Published: May 2024

Damage to the ribosome or an imbalance in protein biosynthesis can lead to some human diseases, such as diabetic retinopathy (DR) and other eye diseases. Here, we reported that the kri1l gene was responsible for retinal development. The kri1l gene encodes an essential component of the rRNA small subunit processome. The retinal structure was disrupted in kri1l mutants, which resulted in small eyes. The boundaries of each layer of cells in the retina were blurred, and each layer of cells was narrowed and decreased. The photoreceptor cells and Müller glia cells almost disappeared in kri1l mutants. The lack of photoreceptor cells caused a fear of light response. The development of the retina started without abnormalities, and the abnormalities began two days after fertilization. In the kri1l mutant, retinal cell differentiation was defective, resulting in the disappearance of cone cells and Müller cells. The proliferation of retinal cells was increased, while apoptosis was also enhanced in kri1l mutants. γ-H2AX upregulation indicated the accumulation of DNA damage, which resulted in cell cycle arrest and apoptosis. The kri1l mutation reduced the expression of some opsin genes and key retinal genes, which are also essential for retinal development.
Bridging the gap with multispecific immune cell engagers in cancer and infectious diseases
Authors: Rolin Camille , Zimmer Jacques , Seguin-Devaux Carole
Published: May 2024

By binding to multiple antigens simultaneously, multispecific antibodies are expected to substantially improve both the activity and long-term efficacy of antibody-based immunotherapy. Immune cell engagers, a subclass of antibody-based constructs, consist of engineered structures designed to bridge immune effector cells to their target, thereby redirecting the immune response toward the tumor cells or infected cells. The increasing number of recent clinical trials evaluating immune cell engagers reflects the important role of these molecules in new therapeutic approaches for cancer and infections. In this review, we discuss how different immune cell types (T and natural killer lymphocytes, as well as myeloid cells) can be bound by immune cell engagers in immunotherapy for cancer and infectious diseases. Furthermore, we explore the preclinical and clinical advancements of these constructs, and we discuss the challenges in translating the current knowledge from cancer to the virology field. Finally, we speculate on the promising future directions that immune cell engagers may take in cancer treatment and antiviral therapy.
Environment modulates protein heterogeneity through transcriptional and translational stop codon readthrough
Authors: Romero Romero Maria Luisa , Poehls Jonas , Kirilenko Anastasiia , Richter Doris , Jumel Tobias , Shevchenko Anna , Toth-Petroczy Agnes
Published: May 2024

Stop codon readthrough events give rise to longer proteins, which may alter the protein’s function, thereby generating short-lasting phenotypic variability from a single gene. In order to systematically assess the frequency and origin of stop codon readthrough events, we designed a library of reporters. We introduced premature stop codons into mScarlet, which enabled high-throughput quantification of protein synthesis termination errors in E. coli using fluorescent microscopy. We found that under stress conditions, stop codon readthrough may occur at rates as high as 80%, depending on the nucleotide context, suggesting that evolution frequently samples stop codon readthrough events. The analysis of selected reporters by mass spectrometry and RNA-seq showed that not only translation but also transcription errors contribute to stop codon readthrough. The RNA polymerase was more likely to misincorporate a nucleotide at premature stop codons. Proteome-wide detection of stop codon readthrough by mass spectrometry revealed that temperature regulated the expression of cryptic sequences generated by stop codon readthrough in E. coli. Overall, our findings suggest that the environment affects the accuracy of protein production, which increases protein heterogeneity when the organisms need to adapt to new conditions.
Validation of human telomere length multi-ancestry meta-analysis association signals identifies POP5 and KBTBD6 as human telomere length regulation genes
Authors: Keener Rebecca , Chhetri Surya B. , Connelly Carla J. , Taub Margaret A. , Conomos Matthew P. , Weinstock Joshua , Ni Bohan , Strober Benjamin , Aslibekyan Stella , Auer Paul L. , Barwick Lucas , Becker Lewis C. , Blangero John , Bleecker Eugene R. , Brody Jennifer A. , Cade Brian E. , Celedon Juan C. , Chang Yi-Cheng , Cupples L. Adrienne , Custer Brian , Freedman Barry I. , Gladwin Mark T. , Heckbert Susan R. , Hou Lifang , Irvin Marguerite R. , Isasi Carmen R. , Johnsen Jill M. , Kenny Eimear E. , Kooperberg Charles , Minster Ryan L. , Naseri Take , Viali Satupa’itea , Nekhai Sergei , Pankratz Nathan , Peyser Patricia A. , Taylor Kent D. , Telen Marilyn J. , Wu Baojun , Yanek Lisa R. , Yang Ivana V. , Albert Christine , Arnett Donna K. , Ashley-Koch Allison E. , Barnes Kathleen C. , Bis Joshua C. , Blackwell Thomas W. , Boerwinkle Eric , Burchard Esteban G. , Carson April P. , Chen Zhanghua , Chen Yii-Der Ida , Darbar Dawood , de Andrade Mariza , Ellinor Patrick T. , Fornage Myriam , Gelb Bruce D. , Gilliland Frank D. , He Jiang , Islam Talat , Kaab Stefan , Kardia Sharon L. R. , Kelly Shannon , Konkle Barbara A. , Kumar Rajesh , Loos Ruth J. F. , Martinez Fernando D. , McGarvey Stephen T. , Meyers Deborah A. , Mitchell Braxton D. , Montgomery Courtney G. , North Kari E. , Palmer Nicholette D. , Peralta Juan M. , Raby Benjamin A. , Redline Susan , Rich Stephen S. , Roden Dan , Rotter Jerome I. , Ruczinski Ingo , Schwartz David , Sciurba Frank , Shoemaker M. Benjamin , Silverman Edwin K. , Sinner Moritz F. , Smith Nicholas L. , Smith Albert V. , Tiwari Hemant K. , Vasan Ramachandran S. , Weiss Scott T. , Williams L. Keoki , Zhang Yingze , Ziv Elad , Raffield Laura M. , Reiner Alexander P. ,   NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium,   TOPMed Hematology and Hemostasis Working Group,   TOPMed Structural Variation Working Group, Arvanitis Marios , Greider Carol W. , Mathias Rasika A. , Battle Alexis
Published: May 2024

Genome-wide association studies (GWAS) have become well-powered to detect loci associated with telomere length. However, no prior work has validated genes nominated by GWAS to examine their role in telomere length regulation. We conducted a multi-ancestry meta-analysis of 211,369 individuals and identified five novel association signals. Enrichment analyses of chromatin state and cell-type heritability suggested that blood/immune cells are the most relevant cell type to examine telomere length association signals. We validated specific GWAS associations by overexpressing KBTBD6 or POP5 and demonstrated that both lengthened telomeres. CRISPR/Cas9 deletion of the predicted causal regions in K562 blood cells reduced expression of these genes, demonstrating that these loci are related to transcriptional regulation of KBTBD6 and POP5. Our results demonstrate the utility of telomere length GWAS in the identification of telomere length regulation mechanisms and validate KBTBD6 and POP5 as genes affecting telomere length regulation.