bluuebunny/crossref_metadata_2025 huggingface dataset:
Limited availability of methods for the detection of xenotransplantation‐relevant viruses in veterinary laboratories
Authors: Denner Joachim
Published: May 2024

Background

The German Xenotransplantation Consortium is in the process to prepare a clinical trial application (CTA) on xenotransplantation of genetically modified pig hearts. In the CTA documents to the central and national regulatory authorities, that is, the European Medicines Agency (EMA) and the Paul Ehrlich Institute (PEI), respectively, it is required to list the potential zoonotic or xenozoonotic porcine microorganisms including porcine viruses as well as to describe methods of detection in order to prevent their transmission. The donor animals should be tested using highly sensitive detection systems. I would like to define a detection system as the complex including the actual detection methods, either PCR‐based, cell‐based, or immunological methods and their sensitivity, as well as sample generation, sample preparation, sample origin, time of sampling, and the necessary negative and positive controls. Lessons learned from the identification of porcine cytomegalovirus/porcine roseolovirus (PCMV/PRV) in the xenotransplanted heart in the recipient in the Baltimore study underline how important such systems are. The question is whether veterinary laboratories can supply such assays.

Methods

A total of 35 veterinary laboratories in Germany were surveyed for their ability to test for selected xenotransplantation‐relevant viruses, including PCMV/PRV, hepatitis E virus, and porcine endogenous retrovirus‐C (PERV‐C). As comparison, data from Swiss laboratories and a laboratory in the USA were analyzed. Furthermore, we assessed which viruses were screened for in clinical and preclinical trials performed until now and during screening of pig populations.

Results

Of the nine laboratories that provided viral diagnostics, none of these included all potential viruses of concern, indeed, the most important assays confirmed in recent human trials, antibody detection of PCMV/PRV and screening for PERV‐C were not available at all. The situation was similar in Swiss and US laboratories. Different viruses have been tested for in first clinical and preclinical trials performed in various countries.

Conclusion

Based on these results it is necessary to establish special virological laboratories able to test for all xenotransplantation‐relevant viruses using validated assays, optimally in the xenotransplantation centers.
Memes and Constructions of TikTok Culture in #DontPlayPlayBosku
Authors: Tanjung Sumekar
Published: May 2024

Memes have become a medium to convey messages on TikTok. However, memes are often underestimated. The researcher has noticed that TikTok is not merely a platform as it is also a memetic, complex text. As a platform, TikTok not only mediates and facilitates the production of short videos but also becomes a culture. Through the Don't Play Play Bosku audio meme phenomenon, this study aims to provide a perspective on how meme themes are conveyed to the public to create a high engagement space and what sorts of ideology are offered by creators in the TikTok culture space. The researcher conducted digital ethnographic observations, qualitative content analysis, and used the Shifman’s three-dimension approach to analyze 10 video samples qualitatively. This study found three meme themes, including inadequacy, metaphor and a practice of playfulness, and mental satire. At the content level, memes are not only an expression of videos but also an audio control to negotiate. At the form level, memes are delivered with word twists, reactions, and effects frequently repeated. The practice of memes at the stance level indicates that the ideological position of creators in bringing up memes is an elaboration of videos and audio that give birth to these three themes in the mechanism of TikTok culture. Memes as a TikTok culture is a culture that is actively produced and continuously consumed. The construction of TikTok culture is formed from the rituals shared in algorithm-framed imitation and replication.
The Impact of Social Media the Dissemination and Teaching of Mandarin Language: A Systematic Review
Authors: Wang Yu Ting , Khairie bin Ahmad Mohd. , Liu Tinglei
Published: May 2024

In the current digital landscape, social media has emerged as a vital conduit for the dissemination of information and the sharing of resources, demonstrating significant potential for language acquisition. This investigation delves into the impact and utility of social media in the arena of learning mandarin as a second language. Through a systematic examination of 29 scholarly articles, this study concentrates on the strategic employment of various social media platforms, including WeChat and Facebook, to furnish learners of mandarin with an authentic and immediate educational milieu, thereby facilitating the enhancement of their communicative proficiency. The sentence examines the unique characteristics and limitations of various digital learning environments in Mandarin language education. It suggests strategies to overcome cultural and technological challenges, aiming to improve teaching methods and the spread of the Mandarin language. The insights gleaned from this research will furnish mandarin language instructors and digital media analysts with a framework to foster pedagogical innovation in the digital epoch.
Exploring the Dynamics of Miscommunication between Arabic and English in Economic Discourse
Authors: Al-Tarawneh Alalddin
Published: May 2024

The main goal of this study is to gain a comprehensive understanding of the complex and diverse dynamics of miscommunication that occur during economic discussions between Arabic and English languages. By exploring this topic, the study aims to shed light on important questions about the origins of these misunderstandings and their effects on economic interactions. To achieve this objective, the research will draw upon valuable insights from previous agreements, intercultural bargaining, and global economic relations. It is crucial to emphasize that economic misunderstandings in conversations arise from various factors, including differences in language structure, disparities in cultural backgrounds, and varying contexts. These elements contribute to the confusion surrounding economic terminology, such as sentence structure, vocabulary and meaning difficulties, and contrasting communication styles. The research also examines the influence of cultural nuances and investigates how past events, cultural practices, and societal legacies shape the understanding of economic terms. The importance of effective communication in promoting trust and facilitating successful economic collaboration cannot be overstated. It goes beyond the economic implications of unfavorable trade terms and strained international relations. This research delves into the challenges faced by interpreters and negotiators, highlighting how technology can either alleviate or exacerbate the issue of miscommunication. Ultimately, it serves as a reminder that managers' misunderstandings play a pivotal role in economic dialogues. In today's interconnected global economy, clear and precise communication is essential for productive negotiations and the maintenance of long-lasting international business relationships. To address this, we propose proactive measures such as supporting training programs, leveraging technology wisely, and demonstrating a strong commitment to intercultural communication. The study underscores the significance of adopting effective communication strategies to navigate complex economic conversations and uphold harmonious global economic relationships in an ever-changing world.
Platform Dependency in the Big Tech Era: Lessons from Australian Facebook Blackout and Botswana Implications
Authors: Ditlhokwa Gopolang , Cann Victoria Elizabeth
Published: May 2024

The surge in social media usage for news consumption has led to a heightened reliance on these platforms for accessing information worldwide. In Botswana, Facebook has become one of the primary channels for news consumption, mirroring trends seen in various nations. However, the 2021 Australian Facebook conflict exposed the risks associated with over-reliance on such platforms for news dissemination. In this paper, we investigate the phenomenon of platform dependency, specifically examining the implications for Botswana, in the wake of the Australian Facebook news blackout. Employing a stratified sampling approach, data was gathered by tracking the volume of news posts shared across 51 selected Facebook pages throughout February 2021. The findings revealed a noteworthy trend, with an average of 5630 news items posted or shared on the platform within four weeks. This marked a growing reliance on Facebook-exclusive pages for news consumption, with minimal engagement observed on alternative websites. We argue that there is a precarious position of pages solely reliant on Facebook for news sharing, especially amidst escalating big data politics and regulatory measures that target Tech Giants. Consequently, these pages face an uncertain future, potentially hampering access to vital news reporting and information-sharing to the adaptive population. Currently, in Botswana, there is a notable dearth of academic exploration into the regulation of Big Tech and its potential repercussions for the nation. Thus, this study serves as a cornerstone in pursuing this significant area of inquiry.
Myostatin gene invalidation does not prevent skeletal muscle mass loss during experimental sepsis in mice
Authors: Morel Jérome , Pignard Anne Sophie , Castells Josiane , Allibert Valentine , Hatimi Lahcène , Buhot Benjamin , Velarde Mathias , Durieux Anne Cécile , Freyssenet Damien
Published: May 2024

Loss of muscle mass and function induced by sepsis contributes to physical inactivity and disability in intensive care unit patients. Limiting skeletal muscle deconditioning may thus be helpful in reducing the long‐term effect of muscle wasting in patients. We tested the hypothesis that invalidation of the myostatin gene, which encodes a powerful negative regulator of skeletal muscle mass, could prevent or attenuate skeletal muscle wasting and improve survival of septic mice. Sepsis was induced by caecal ligature and puncture (CLP) in 13‐week‐old C57BL/6J wild‐type and myostatin knock‐out male mice. Survival rates were similar in wild‐type and myostatin knock‐out mice seven days after CLP. Loss in muscle mass was also similar in wild‐type and myostatin knock‐out mice 4 and 7 days after CLP. The loss in muscle mass was molecularly supported by an increase in the transcript level of E3‐ubiquitin ligases and autophagy–lysosome markers. This transcriptional response was blunted in myostatin knock‐out mice. No change was observed in the protein level of markers of the anabolic insulin/IGF1‐Akt‐mTOR pathway. Muscle strength was similarly decreased in wild‐type and myostatin knock‐out mice 4 and 7 days after CLP. This was associated with a modified expression of genes involved in ion homeostasis and excitation–contraction coupling, suggesting that a long‐term functional recovery following experimental sepsis may be impaired by a dysregulated expression of molecular determinants of ion homeostasis and excitation–contraction coupling. In conclusion, myostatin gene invalidation does not provide any benefit in preventing skeletal muscle mass loss and strength in response to experimental sepsis.

image

Key points

Survival rates are similar in wild‐type and myostatin knock‐out mice seven days after the induction of sepsis.

Loss in muscle mass and muscle strength are similar in wild‐type and myostatin knock‐out mice 4 and 7 days after the induction of an experimental sepsis.

Despite evidence of a transcriptional regulation, the protein level of markers of the anabolic insulin/IGF1‐Akt‐mTOR pathway remained unchanged.

RT‐qPCR analysis of autophagy–lysosome pathway markers indicates that activity of the pathway may be altered by experimental sepsis in wild‐type and myostatin knock‐out mice.

Experimental sepsis induces greater variations in the mRNA levels of wild‐type mice than those of myostatin knock‐out mice, without providing any significant catabolic resistance or functional benefits.
Exercise‐induced cortical disinhibition mediates the relationship between fitness and memory in older adults
Authors: Cadwallader Claire J. , Curtin Dylan , Taylor Eleanor M. , de Moel Tamar , Jarvis Huw , Hutchison Christopher , Hendrikse Joshua , Chong Trevor T.‐J. , Coxon James P.
Published: May 2024

Regular exercise benefits learning and memory in older adults, but the neural mechanisms mediating these effects remain unclear. Evidence in young adults indicates that acute exercise creates a favourable environment for synaptic plasticity by enhancing cortical disinhibition. As such, we investigated whether plasticity‐related disinhibition mediated the relationship between cardiorespiratory fitness and memory function in healthy older adults (n = 16, mean age = 66.06). Participants completed a graded maximal exercise test and assessments of visual and verbal memory, followed by two counterbalanced sessions involving 20 min of either high‐intensity interval training exercise or rest. Disinhibition was measured following intermittent theta burst stimulation via paired‐pulse transcranial magnetic stimulation. In line with our hypotheses, we observed a positive correlation between cardiorespiratory fitness and verbal memory, which was mediated by plasticity‐related cortical disinhibition. Our novel finding implicates cortical disinhibition as a mechanism through which the effects of acute bouts of exercise may translate to improved memory in older adults. This finding extends current understanding of the physiological mechanisms underlying the positive influence of cardiorespiratory fitness for memory function in older adults, and further highlights the importance of promoting exercise engagement to maintain cognitive health in later life.

image

Key points

There are well established benefits of regular exercise for memory function in older adults, but the mechanisms are unclear. Cortical disinhibition is important for laying down new memories, and is enhanced following acute exercise in young adults, suggesting it is a potential mechanism underlying these benefits in ageing.

Older adults completed a fitness test and assessments of memory, followed by two sessions involving either 20 min of exercise or rest. Disinhibition was measured following intermittent theta burst stimulation via paired‐pulse transcranial magnetic stimulation.

Cardiorespiratory fitness was positively associated with memory performance. Higher fitness was associated with enhanced cortical disinhibition following acute exercise.

Cortical disinhibition completely mediated the relationship between fitness and memory.

This novel finding provides a mechanistic account for the positive influence of cardiorespiratory fitness on memory in later life, and emphasises the importance of regular exercise for cognitive health in older populations.
Enhanced Euler–Lagrange Formulation for Analyzing Human Gait With Moving Base Reference
Authors: Chander Sekar Anup , Mukherjee Ashutosh , Shivling Vhatkar Dattatraya , Singla Ashish
Published: May 2024

Euler–Lagrange's formulation is known for its systematic and simplified approach to deriving dynamics of complex systems. In order to apply the existing formulation to human gait dynamics, the base reference frame must be assumed as an inertial reference frame. Conventionally, the ankle joints or the hip joints are regarded as base reference frames during the stance and swing phases of human walking. As these joints are non-inertial in nature during actual locomotion, this assumption could result in inaccurate calculation of lower-limb joint torques and forces. Therefore, in this paper, an existing Euler–Lagrange-based formulation originally developed for fixed-base robotic manipulators is considered and modified to accommodate the movement of the base reference frame with respect to an inertial frame of reference defined outside the human body. The applicability of the modified formulation is studied, implemented, and validated using three standard and publicly available gait datasets covering the phases of walking and running. The joint torques obtained using the proposed dynamic model are compared with reference torques by calculating the mean absolute error values and visually through Bland–Altman plots. The obtained joint torque values and plots indicate a close agreement with published torques, thereby validating the accuracy of the proposed dynamic model. The robust formulation implementation makes it a valuable resource for researchers in this field, offering a reliable framework for gait analysis and the design of lower-limb prosthetics or exoskeletons.
Three-Dimensional Profile Reconstruction and Internal Defect Detection of Silicon Wafers Using Cascaded Fiber Optic Fabry–Pérot Interferometer and Leaky Field Detection Technologies
Authors: Zhou Fengfeng , Fu Xingyu , Chen Siying , Han Changheon , Jun Martin B. G.
Published: May 2024

Wafer quality control is one of the important processes to improve the yield rate of semiconductor products. Profile quality and defects in the wafer are two key factors that should be taken into consideration. In this research, we introduce a method that measures the profile of the upper surface and the thickness of the wafer at the same time using an optical fiber cascaded Fabry–Pérot interferometer working at wavelength of 1550 nm. Therefore, the 3D profile of the wafer can be reconstructed directly. Testing results show that both accuracy and precision of the Fabry–Pérot interferometer are within a nanometer scale. Defects, especially those embedded inside the wafer, will be detected by monitoring the leaky field with treating wafers as slab waveguides. With the leaky field detection, defects on the lower surface of the wafer were successfully detected by monitoring the leaky field above the upper surface of the wafer. Compared with traditional methods such as radiographic testing or computed tomography testing, the proposed methods provide a cost-effective alternative for wafer quality evaluation.
Stochastic Defect Localization for Cooperative Additive Manufacturing Using Gaussian Mixture Maps
Authors: Rescsanski Sean , Shah Vihaan , Tang Jiong , Imani Farhad
Published: May 2024

Robotic additive manufacturing (RAM) offers significant improvements in maximum build volume compared to conventional bounded designs (e.g., gantry) by leveraging high degrees-of-freedom machines and multi-robot cooperation. However, cooperative RAM suffers from the same defect generation challenges as conventional systems, necessitating improvements in the detection and prevention of flaws within fabricated components. Quality assurance can be further bolstered through the integration of AM models, which utilize sensor feedback to localize defects, vastly reducing false positives. This research explores defect localization through a novel dynamic defect model created from simulated sensing data. In particular, two cooperative robots are simulated to estimate defect parameters, while observing the workspace and accurately classifying different regions of the part, generating a Gaussian mixture map that identifies and assigns appropriate actions based on defect types and characteristics. The experimental result shows that the implementation of the dynamic defect model and selective reevaluation achieved an effective defect detection accuracy of 99.9%, an improvement of 9.9% without localization. The proposed framework holds potential for application in domains that utilize high degrees-of-freedom machines and collaborative agents, offering scalability, improved fabrication speeds, and enhanced mechanical properties.
The correlation between time-intensity curve parameters of transrectal contrast-enhanced ultrasound and pathological prognostic factors in rectal adenocarcinoma
Authors: Su Shitao , Huang Jianyuan , Huang Xuanzhang , Li Xigui , Liu Yaoli , Meng Jun , Fan Yu , He Xiaoyan , Zhu Shangyong
Published: May 2024

Aims: To investigate the correlation between time-intensity curve (TIC) parameters obtained from transrectal contrast-enhanced ultrasound (TR-CEUS) and important pathological prognostic factors in rectal adenocarcinoma.Material and methods: We retrospectively included 477 patients with pathologically confirmed rectal adenocarcinoma. TIC parameters were derived from preoperative dynamic TR-CEUS images. These parameters included peak intensity (PI), time to peak (TTP),mean transit time (MTT), slope (S), and area under the curve (AREA). Pathological prognostic factors included TN stage, tumor diameter, lymphovascular invasion (LVI), perineural invasion, and tumor differentiation. Spearman’s correlation analysis and binary logistic regression were used to analyze the association between TIC parameters and pathological prognostic factors.Results: pT1-2 stages rectal carcinomas exhibited higher PI-max, PI-min, S-max, S-min, AREA-max, and AREA-min than pT3-4 stages (all p<0.05). pN0 stage rectal adenocarcinomas displayed higher PI-max, S-max, AREA-max, PI-ratio, Sratio, and AREA-ratio than pN1-2 stage (all p<0.05). PI-ratio and S-ratio were higher in the LVI-negative and tumor diameter ≥4cm group compared to the LVI-positive and tumor diameter <4cm group, respectively (p<0.05). Well-differentiated rectal adenocarcinomas displayed higher PI-max, AREA-max, PI-ratio, S-ratio, and AREA-ratio than the moderate-poor differentiated group (all p<0.05). PI-max, S-max, AREA-max, PI-ratio, S-ratio, and AREA-ratio were negatively correlated with pN stage (all p<0.05). PI-ratio and S-ratio were independent predictive factors for the pN stage (OR=0.774, OR=1.048). S-ratio and AREA-ratio were independent predictive factors for tumor differentiation (OR=1.071, OR=0.911).Conclusions: TIC parameters derived from TR-CEUS exhibit correlations with specific pathological prognostic factors in rectal adenocarcinomas. This non-invasive method may hold promise for preoperatively assessing the prognosis of rectal adenocarcinoma patients.
Morphological variation and abnormalities in two species of Typhlodromus Scheuten (Acari: Phytoseiidae)

Authors: Afkhami Maryam , Farazmand Azadeh , Faraji Farid
Published: May 2024

Typhlodromus (Anthoseius) bagdasarjani Wainstein & Arutunjan and T. (A.) khosrovensis Arutunjan have been frequently recorded from Iran. While investigating the population dynamics of these two predatory mite species on white mulberry in 2022 and 2023, in Tehran (Iran), our study unveiled intriguing morphological abnormalities and variations. Specifically, variations were observed in the number of dorsal shield solenostomes, insertion of ventrianal setae, shape of spermatheca and length of peritreme. In this context, detailed re-descriptions for both species are presented, accompanied by documentation of the observed abnormalities and variations.
Electroconductive and photoelectric properties of Pt/(100) β-Ga2O3 Schottky barrier diode based on Czochralski grown crystal
Authors: Almaev Aleksei , Nikolaev Vladimir , Yakovlev Nikita , Butenko Pavel , Tsymbalov Alexander , Boiko Michael , Kopyev Viktor , Krymov Vladimir , Kushnarev Bogdan , Shapenkov Sevastian , Sharkov Michael , Zarichny Anton
Published: May 2024

Pt/(100) β-Ga2O3 Schottky barrier diodes were fabricated using a plate cleaved from the crystal grown by Czochralski method. Their electroconductive and photoelectric characteristics were studied. The following values were obtained: the Schottky barrier height (1.69/1.62/1.74 eV), ideality coefficient (1.09/1.14), saturation current density (9.91 × 10–15 A/cm2), diode series resistance (7.98 kΩ), and net donor concentration [(1.8–2.4) × 1018 cm–3]. The diodes demonstrate a high rectification ratio of 1010 at an applied voltage of ± 1 V and a relatively low experimental value of the leakage current density ∼10–11 A/cm2. These structures are solar-blind and also capable of operating in self-powered mode. The diodes are highly sensitive to short-wave ultraviolet radiation with a wavelength λ ≤ 265 nm. The maximum values of responsivity (20.4 A/W), external quantum efficiency (1.2 × 104%), and detectivity (9.6 × 1015 Hz0.5 × cm × W–1) of diodes were registered under exposure to irradiation at λ = 210 nm and at applied voltage of −1 V. The responsivity and external quantum efficiency values in the self-powered operation mode were 12.3 A/W and 7.2 × 103%, respectively. The diodes showed low rise and decay times in self-powered operation mode for photodiode based on Ga2O3: 14 and 30 ms, respectively.
Quantification and mitigation of the effect of resynchronization errors in ultrasound sensor network for passive imaging in elastic plates
Authors: Bouchakour Omar , Moulin Emmanuel , Chehami Lynda , Smagin Nikolay
Published: May 2024

The problem of signal desynchronization in passive imaging based on noise correlation for defect detection in elastic plates is investigated. Although a post-processing resynchronization process relying on the symmetry of noise correlation functions can be applied prior to the imaging algorithm, perfect synchronization might not be achieved experimentally. Effect of such residual synchronization errors on the defect detection performance is quantified as a function of their probability density function. A mathematical regularization process is then proposed to reduce the standard deviation of the resynchronization errors by a factor of N−1/N (N is the number of sensors), which results in a significant improvement in the detection performance. Finally, these theoretical results are validated through a simple flexural-wave propagation simulation.
Enhancing ecosystem productivity and stability with increasing canopy structural complexity in global forests
Authors: Liu Xiaoqiang , Feng Yuhao , Hu Tianyu , Luo Yue , Zhao Xiaoxia , Wu Jin , Maeda Eduardo E. , Ju Weiming , Liu Lingli , Guo Qinghua , Su Yanjun
Published: May 2024

Forest canopy structural complexity (CSC) plays a crucial role in shaping forest ecosystem productivity and stability, but the precise nature of their relationships remains controversial. Here, we mapped the global distribution of forest CSC and revealed the factors influencing its distribution using worldwide light detection and ranging data. We find that forest CSC predominantly demonstrates significant positive relationships with forest ecosystem productivity and stability globally, although substantial variations exist among forest ecoregions. The effects of forest CSC on productivity and stability are the balanced results of biodiversity and resource availability, providing valuable insights for comprehending forest ecosystem functions. Managed forests are found to have lower CSC but more potent enhancing effects of forest CSC on ecosystem productivity and stability than intact forests, highlighting the urgent need to integrate forest CSC into the development of forest management plans for effective climate change mitigation.
Molecular beacon–based detection of circulating microRNA-containing extracellular vesicle as an α-synucleinopathy biomarker
Authors: Yu Zhenwei , Zheng Yuanchu , Cai Huihui , Li Siming , Liu Genliang , Kou Wenyi , Yang Chen , Cao Shuangshuang , Chen Lei , Liu Xuedong , Wan Zhirong , Zhang Ning , Li Xiaohong , Cui Guiyun , Chang Ying , Huang Yue , Lv Hong , Feng Tao
Published: May 2024

Early and precise diagnosis of α-synucleinopathies is challenging but critical. In this study, we developed a molecular beacon–based assay to evaluate microRNA-containing extracellular vesicles (EVs) in plasma. We recruited 1203 participants including healthy controls (HCs) and patients with isolated REM sleep behavior disorder (iRBD), α-synucleinopathies, or non–α-synucleinopathies from eight centers across China. Plasma miR-44438–containing EV levels were significantly increased in α-synucleinopathies, including those in the prodromal stage (e.g., iRBD), compared to both non–α-synucleinopathy patients and HCs. However, there are no significant differences between Parkinson’s disease (PD) and multiple system atrophy. The miR-44438–containing EV levels negatively correlated with age and the Hoehn and Yahr stage of PD patients, suggesting a potential association with disease progression. Furthermore, a longitudinal analysis over 16.3 months demonstrated a significant decline in miR-44438–containing EV levels in patients with PD. These results highlight the potential of plasma miR-44438–containing EV as a biomarker for early detection and progress monitoring of α-synucleinopathies.
Changes in monsoon precipitation in East Asia under a 2°C interglacial warming
Authors: Gao Xinbo , Hao Qingzhen , Wang Luo , Song Yang , Ge Junyi , Wu Haibin , Xu Bing , Han Long , Fu Yu , Wu Xuechao , Deng Chenglong , Guo Zhengtang
Published: May 2024

Past intervals of warming provide the unique opportunity to observe how the East Asia monsoon precipitation response happened in a warming world. However, the available evaluations are primarily limited to the last glacial-to-interglacial warming, which has fundamental differences from the current interglacial warming, particularly in changes in ice volume. Comparative paleoclimate studies of earlier warm interglacial periods can provide more realistic analogs. Here, we present high-resolution quantitative reconstructions of temperature and precipitation from north-central China over the past 800 thousand years. We found that the average precipitation increase, estimated by the interglacial data, was only around one-half of that estimated for the glacial-to-interglacial data, which is attributed to the amplification of climate change by ice volume variations. Analysis of the interglacial data suggests an increase in monsoon precipitation of ~100 mm for a warming level of 2°C on the Chinese Loess Plateau.
Volumetric microscopy of cerebral arteries with a miniaturized optical coherence tomography imaging probe
Authors: Pereira Vitor M. , Lylyk Pedro , Cancelliere Nicole , Lylyk Pedro N. , Lylyk Ivan , Anagnostakou Vania , Bleise Carlos , Nishi Hidehisa , Epshtein Mark , King Robert M. , Shazeeb Mohammed Salman , Puri Ajit S. , Liang Conrad W. , Hanel Ricardo A. , Spears Julian , Marotta Thomas R. , Lopes Demetrius K. , Gounis Matthew J. , Ughi Giovanni J.
Published: May 2024

Endovascular interventions are increasingly becoming the preferred approach for treating strokes and cerebral artery diseases. These procedures rely on sophisticated angiographical imaging guidance, which encounters challenges because of limited contrast and spatial resolution. Achieving a more precise visualization of the underlying arterial pathology and neurovascular implants is crucial for accurate procedural decision-making. In a human study involving 32 patients, we introduced the clinical application of a miniaturized endovascular neuro optical coherence tomography (
n
OCT) imaging probe. This technology was designed to navigate the tortuous paths of the cerebrovascular circulation and to offer high-resolution imaging in situ. The
n
OCT probe is compatible with standard neurovascular microcatheters, integrating with the procedural workflow used in clinical routine. Equipped with a miniaturized optical fiber and a distal lens, the probe illuminates the tissue and collects the backscattered, near-infrared light. While rotating the fiber and the lens at high speed, the probe is rapidly retracted, creating a spiral-shaped light pattern to comprehensively capture the arterial wall and implanted devices. Using
n
OCT, we demonstrated volumetric microscopy of cerebral arteries in patients undergoing endovascular procedures. We imaged the anterior and posterior circulation of the brain, including distal segments of the internal carotid and middle-cerebral arteries, as well as the vertebral, basilar, and posterior cerebral arteries. We captured a broad spectrum of neurovascular pathologies, such as brain aneurysms, ischemic stroke, arterial stenoses, dissections, and intracranial atherosclerotic disease.
n
OCT offered artifact-free, high-resolution visualizations of intracranial artery pathology and neurovascular devices.
Gentamicin concentration and acute kidney injury in term neonates treated for neonatal sepsis with gentamicin and ampicillin-cloxacillin combination
Authors: James Masanyiwa Ernest , Naburi Helga , Mugusi Sabina , Kunambi Peter P. , Mwakyandile Tosi , Mnkugwe Rajabu Hussein , Khalfan Mohamed Ally , Moshi Mainen J. , Minzi Omary M. , Sasi Philip
Published: May 2024

Gentamicin is widely used to treat neonatal infections caused by both Gram-negative and Gram-positive bacteria, and the WHO recommends its use while monitoring serum creatinine and gentamicin concentrations to avoid drug-induced nephrotoxicity and ototoxicity. Yet in some resource-limited settings, the drug is used without monitoring. A population pharmacokinetics study involving term neonates with neonatal infection admitted to a neonatal unit. Participants were started on intravenous gentamicin 5 mg/kg once a day in combination with ampicilin-cloxacillin. Blood samples for serum gentamicin concentration were taken at 0.25, 0.5, 1, 2, 3, 5, 6, 8, 10, 12, 14, 16, 18, 20, 23, and 24 hours after the initial dose, each participant contributing two samples to the 24 hour sampling schedule. An additional sample for trough concentration was taken from each participant just before the third gentamicin dose while serum creatinine concentration was measured before and after treatment. Twenty-four participants were enrolled into the study and included in the final analysis. Mean (SD) peak and trough serum gentamicin concentrations were 16.66 (0.64) µg/mL and 3.28 (0.70) µg/mL, respectively. Gentamicin clearance (CL) was 0.40 mL min
−1
kg
−1
and volume of distribution (VD) was 0.31 L kg
−1
. Mean (SD) serum creatinine level after treatment was 209.7 (70.4) µmol/L compared to 103.3 (23.6) µmol/L before treatment [mean difference (106.4 ± 67.1; 95% confidence interval (CI): 78.1; 134.7 µmol/L; t (23) = 7.77;
P
< 0.001]. All participants fulfilled the Kidney Disease Improving Global Outcomes (KDIGO) criteria for acute kidney injury after treatment. Treatment of neonatal infection with antimicrobial regimen containing gentamicin, without renal function and gentamicin concentration monitoring, carries a significant risk for drug-induced acute kidney injury.
Tuning interdomain conjugation to enable
in situ
population modification in yeasts
Authors: Stindt Kevin R. , McClean Megan N.
Published: May 2024

The ability to modify and control natural and engineered microbiomes is essential for biotechnology and biomedicine. Fungi are critical members of most microbiomes, yet technology for modifying the fungal members of a microbiome has lagged far behind that for bacteria. Interdomain conjugation (IDC) is a promising approach, as DNA transfer from bacterial cells to yeast enables
in situ
modification. While such genetic transfers have been known to naturally occur in a wide range of eukaryotes and are thought to contribute to their evolution, IDC has been understudied as a technique to control fungal or fungal-bacterial consortia. One major obstacle to the widespread use of IDC is its limited efficiency. In this work, we manipulated metabolic and physical interactions between genetically tractable
Escherichia coli
and
Saccharomyces cerevisiae
to control the incidence of IDC. We test the landscape of population interactions between the bacterial donors and yeast recipients to find that bacterial commensalism leads to maximized IDC, both in culture and in mixed colonies. We demonstrate the capacity of cell-to-cell binding via mannoproteins to assist both IDC incidence and bacterial commensalism in culture and model how these tunable controls can predictably yield a range of IDC outcomes. Furthermore, we demonstrate that these controls can be utilized to irreversibly alter a recipient yeast population, by both “rescuing” a poor-growing recipient population and collapsing a stable population via a novel IDC-mediated CRISPR/Cas9 system.

IMPORTANCE

Fungi are important but often unaddressed members of most natural and synthetic microbial communities. This work highlights opportunities for modifying yeast microbiome populations through bacterial conjugation. While conjugation has been recognized for its capacity to deliver engineerable DNA to a range of cells, its dependence on cell contact has limited its efficiency. Here, we find “knobs” to control DNA transfer, by engineering the metabolic dependence between bacterial donors and yeast recipients and by changing their ability to physically adhere to each other. Importantly, we functionally validate these “knobs” by irreversibly altering yeast populations. We use these controls to “rescue” a failing yeast population, demonstrate the capacity of conjugated CRISPR/Cas9 to depress or collapse populations, and show that conjugation can be easily interrupted by disrupting cell-to-cell binding. These results offer building blocks toward
in situ
mycobiome editing, with significant implications for clinical treatments of fungal pathogens and other fungal system engineering.
Optimizing SARS-CoV-2 vaccine responses in kidney transplant recipients: an urgent need
Authors: Cheng Yi-Ling , Chang Shen-Shin , Chao Chiao-Hsuan , Chen Po-Ta , Lin Ya-Lan , Syu Guan-Da , Lee Nan-Yao , Chen Po-Lin , Ko Wen-Chien , Ho Tzong-Shiann
Published: May 2024

Kidney transplant recipients (KTRs) have been identified as a population at increased risk for severe SARS-CoV-2 infection outcomes. This study focused on understanding the immune response of KTRs post-vaccination, specifically examining both serological and cellular responses to the SARS-CoV-2 vaccine. Thirteen individuals, including seven KTRs and six healthy donors, were evaluated for antibody levels and T cell responses post-vaccination. The study revealed that KTRs had significantly lower serological responses, including reduced anti-receptor binding domain (RBD) binding antibodies and neutralizing antibodies against the Wuhan, Delta, and Omicron BA.2 strains. Additionally, KTRs demonstrated weaker CD8 T cell cytotoxic responses and lower Th1 cytokine secretion, particularly IFN-γ, after stimulation with variant spike peptide pools. These findings highlight the compromised immunity in KTRs post-vaccination and underscore the need for tailored strategies to bolster immune responses in this vulnerable group. Further investigations are warranted into the mechanisms underlying reduced vaccine efficacy in KTRs and potential therapeutic interventions.

IMPORTANCE

Some studies have revealed that KTRs had lower serological response against SARS-CoV-2 than healthy people. Nevertheless, limited studies investigate the cellular response against SARS-CoV-2 in KTRs receiving SARS-CoV-2 vaccines. Here, we found that KTRs have lower serological and cellular responses. Moreover, we found that KTRs had a significantly lower IFN-γ secretion than healthy individuals when their PBMCs were stimulated with SARS-CoV-2 spike peptide pools. Thus, our findings suggested that additional strategies are needed to enhance KTR immunity triggered by the vaccine.
Comparison of the upper and lower airway microbiome in early postoperative lung transplant recipients
Authors: Li Chun-xi , Lv Meng , Liu Hai-yue , Lin Yan-xia , Pan Jian-bing , You Chang-xuan , Su Jin
Published: May 2024

The upper and lower respiratory tract may share microbiome because they are directly continuous, and the nasal microbiome contributes partially to the composition of the lung microbiome. But little is known about the upper and lower airway microbiome of early postoperative lung transplant recipients (LTRs). Using 16S rRNA gene sequencing, we compared paired nasal swab (NS) and bronchoalveolar lavage fluid (BALF) microbiome from 17 early postoperative LTRs. The microbiome between the two compartments were significantly different in Shannon diversity and beta diversity. Four and eight core NS‐associated and BALF‐associated microbiome were identified, respectively. NS samples harbored more
Corynebacterium
,
Acinetobacter,
and
Pseudomonas
, while BALF contained more
Ralstonia
,
Stenotrophomonas
,
Enterococcus,
and
Pedobacter
. The within-subject dissimilarity was higher than the between-subject dissimilarity, indicating a greater impact of sampling sites than sampling individuals on microbial difference. There were both difference and homogeneity between NS and BALF microbiome in early postoperative LTRs. High levels of pathogens were detected in both samples, suggesting that both of them can reflect the diseases characteristics of transplanted lung. The differences between upper and lower airway microbiome mainly come from sampling sites instead of sampling individuals.

IMPORTANCE

Lung transplantation is the only therapeutic option for patients with end-stage lung disease, but its outcome is much worse than other solid organ transplants. Little is known about the NS and BALF microbiome of early postoperative LTRs. Here, we compared paired samples of the nasal and lung microbiome from 17 early postoperative LTRs and showed both difference and homogeneity between the two samples. Most of the “core” microbiome in both NS and BALF samples were recognized respiratory pathogens, suggesting that both samples can reflect the diseases characteristics of transplanted lung. We also found that the differences between upper and lower airway microbiome in early postoperative LTRs mainly come from sampling sites instead of sampling individuals.
Supplemental Material: Fingerprinting enhanced floodplain reworking during the Paleocene–Eocene Thermal Maximum in the Southern Pyrenees (Spain): Implications for channel dynamics and carbon burial
Authors: Prieur Marine , al. et
Published: May 2024

Point-count and grain-size data, method, and LA-ICP-MS U-Pb dating data.  
Comparing generative and retrieval-based chatbots in answering patient questions regarding age-related macular degeneration and diabetic retinopathy
Authors: Cheong Kai Xiong , Zhang Chenxi , Tan Tien-En , Fenner Beau J , Wong Wendy Meihua , Teo Kelvin YC , Wang Ya Xing , Sivaprasad Sobha , Keane Pearse A , Lee Cecilia Sungmin , Lee Aaron Y , Cheung Chui Ming Gemmy , Wong Tien Yin , Cheong Yun-Gyung , Song Su Jeong , Tham Yih Chung
Published: May 2024

Background/aims

To compare the performance of generative versus retrieval-based chatbots in answering patient inquiries regarding age-related macular degeneration (AMD) and diabetic retinopathy (DR).

Methods

We evaluated four chatbots: generative models (ChatGPT-4, ChatGPT-3.5 and Google Bard) and a retrieval-based model (OcularBERT) in a cross-sectional study. Their response accuracy to 45 questions (15 AMD, 15 DR and 15 others) was evaluated and compared. Three masked retinal specialists graded the responses using a three-point Likert scale: either 2 (good, error-free), 1 (borderline) or 0 (poor with significant inaccuracies). The scores were aggregated, ranging from 0 to 6. Based on majority consensus among the graders, the responses were also classified as ‘Good’, ‘Borderline’ or ‘Poor’ quality.

Results

Overall, ChatGPT-4 and ChatGPT-3.5 outperformed the other chatbots, both achieving median scores (IQR) of 6 (1), compared with 4.5 (2) in Google Bard, and 2 (1) in OcularBERT (all p ≤8.4×10−3). Based on the consensus approach, 83.3% of ChatGPT-4’s responses and 86.7% of ChatGPT-3.5’s were rated as ‘Good’, surpassing Google Bard (50%) and OcularBERT (10%) (all p ≤1.4×10−2). ChatGPT-4 and ChatGPT-3.5 had no ‘Poor’ rated responses. Google Bard produced 6.7% Poor responses, and OcularBERT produced 20%. Across question types, ChatGPT-4 outperformed Google Bard only for AMD, and ChatGPT-3.5 outperformed Google Bard for DR and others.

Conclusion

ChatGPT-4 and ChatGPT-3.5 demonstrated superior performance, followed by Google Bard and OcularBERT. Generative chatbots are potentially capable of answering domain-specific questions outside their original training. Further validation studies are still required prior to real-world implementation.
Enhancing equity in access to automated insulin delivery systems in an ethnically and socioeconomically diverse group of children with type 1 diabetes
Authors: Pemberton John , Collins Louise , Drummond Lesley , Dias Renuka P , Krone Ruth , Kershaw Melanie , Uday Suma
Published: May 2024

Introduction

Manufacturer-supported didactic teaching programmes offer effective automated insulin delivery (AID) systems onboarding in children and young people (CYP) with type 1 diabetes (T1D). However, this approach has limited flexibility to accommodate the needs of families requiring additional support.

Research design and methods

Evaluate the efficacy of an inperson manufacturer-supported didactic teaching programme (Group A), in comparison to a flexible flipped learning approach delivered virtually or inperson (Group B). Retrospective analysis of CYP with T1D using continuous glucose monitoring (CGM), who were initiated on AID systems between 2021 and 2023. Compare CGM metrics from baseline to 90 days for both groups A and B. Additionally, compare the two groups for change in CGM metrics over the 90-day period (∆), patient demographics and onboarding time.

Results

Group A consisted of 74 CYP (53% male) with median age of 13.9 years and Group B 91 CYP (54% male) with median age of 12.7 years. From baseline to 90 days, Group A lowered mean (±SD) time above range (TAR, >10.0 mmol/L) from 47.6% (±15.0) to 33.2% (±15.0) (p<0.001), increased time in range (TIR, 3.9–10.0 mmol/L) from 50.4% (±14.0) to 64.7% (±10.2) (p<0.001). From baseline to 90 days, Group B lowered TAR from 51.3% (±15.1) to 34.5% (±11.3) (p<0.001) and increased TIR from 46.5% (±14.5) to 63.7% (±11.0) (p<0.001). There was no difference from baseline to 90 days for time below range (TBR, <3.9 mmol/L) for Group A and Group B. ∆ TAR, TIR and TBR for both groups were comparable. Group B consisted of CYP with higher socioeconomic deprivation, greater ethnic diversity and lower carer education achievement (p<0.05). The majority of Group B (n=79, 87%) chose virtual flipped learning, halving diabetes educator time and increasing onboarding cadence by fivefold.

Conclusions

A flexible virtual flipped learning programme increases onboarding cadence and capacity to offer equitable AID system onboarding.
Gender-transformative programmes: a framework for demonstrating evidence of social impact
Authors: Backman-Levy Jessica K , Greene Margaret Eleanor
Published: May 2024

Ample evidence has demonstrated that gender inequality and restrictive gender norms wield significant influence over health outcomes. While gender-transformative programmes have grown with the aim of challenging these norms and promoting gender equality, their effectiveness in driving sustainable norm change remains a subject of debate. This paper introduces a comprehensive analytical framework designed to assess the impact of these programmes.

Drawing from extensive literature reviews of rigorously evaluated health programmes, this framework identifies four key dimensions that are instrumental in determining a programme’s potential for transformative change. These dimensions are multiplicative effect, sustainability, spread and scalability. Multiplicative effect emphasises the interconnected nature of societal systems, positing that altering one element can trigger cascading effects throughout the entire system. Sustainability recognises that change within a system is less likely to revert once the structure has shifted. Programmes that facilitate norm change are more likely to sustain the changes brought about by their interventions. Spread acknowledges the importance of engaging entire networks that share the targeted norms. Successful programmes should demonstrate evidence of gender-related outcomes extending beyond the immediate beneficiaries, progressively diffusing through the broader population. Finally, scalability emphasises the need to bring gender-transformative initiatives to a larger scale to effect broader norm change.

By aligning programme design and evaluation with these four dimensions, the proposed framework provides a standardised approach for assessing gender-transformative programmes. It shifts the focus from individual-level change to systemic transformation, bridging the gap between programmatic aspirations and the ability to measure genuine progress.