bluuebunny/crossref_metadata_2025 huggingface dataset:
Successful localisation of recurrent thyroid cancer using preoperative patent blue dye injection
Authors: Evranos B. O. , Ince N. , Ataş H. , Polat S. B. , Ahsen H. , Imga N. N. , Dirikoc A. , Topaloglu O. , Tutuncu T. , Ersoy R. , Cakir B.
Published: February 2024

Purpose

In the follow-up of patients with thyroid cancer, recurrences are often detected, posing challenges in locating and removing these lesions in a reoperative setting. This study aimed to assess the effectiveness of preoperative ultrasound (US)-guided injection of patent blue (PB) dye into the recurrences to aid in their safe and efficient removal.

Methods

In this retrospective analysis, we reviewed the records of the patients in a tertiary care centre between February 2019 and March 2023 who underwent US-guided PB injection in the endocrinology outpatient clinic before reoperative neck surgery. The duration between the injection of PB and the initiation of surgery was recorded. The complications and effectiveness of the procedure were evaluated using ultrasonographic, laboratory, surgical, and pathologic records.

Results

We reached 23 consecutive patients with 28 lesions. The recurrences averaged 8.8 mm (4.1–15.6) in size and were successfully stained in all cases. The median time between the PB injection and the incision was 90 (35–210) min. There were no complications related to the dye injection. The blue recurrences were conveniently identified and removed in all cases.

Conclusions

A preoperative US-guided injection of PB is a safe, readily available and highly effective technique for localising recurrent tumours, even in small lesions within scarred reoperative neck surgeries.
Developing a Dynamic Understanding of Risk Factors for People Admitted to Long-term High Dependency Units
Authors: Simpson Adelabu Jonathan , Meaden Alan , Fox Andrew
Published: February 2024

Even with developments in supporting people with enduring psychosis, some people living with these difficulties still require specialised care in inpatient rehabilitation facilities. To optimise the support provided a service evaluation was conducted for people admitted to a Long-term High Dependency Unit service. Data collected routinely with the Short-Term Assessment for Risk and Treatability tool was used to identify dynamic risk factors for the residents. Completed assessments were analysed for frequency and severity of risk behaviours; historic prevalence of risk behaviours; judgements on future risk; and strengths and vulnerabilities. The evaluation indicated a picture of a group of people who have a variety of historic risks and currently engage regularly in aggression and self-neglect, whilst experiencing limited insight, social exclusion, and limited coping abilities. Strengths and vulnerabilities linked to risk behaviours were also grouped into conceptually similar domains to aid intervention. Recommendations are made for using such data to enhance recovery.
How AI hype impacts the LGBTQ + community
Authors: McAra-Hunter Dawn
Published: February 2024

Hype around Artificial Intelligence (AI) has been a feature of this technology since its inception. However, the most recent wave of AI hype has been leveraged to encourage adoption of AI technologies that cause issues for marginalised communities. Hype is also a means to obfuscate real issues of bias, harm, and exploitation felt most sharply by marginalised communities when AI is implemented. This therefore raises the question of power imbalances as a feature of AI technologies as we currently know them. This paper will study the relationship of AI hype and marginalised communities, with particular emphasis on the LGBTQ + community, and look at the way that AI impacts on this community. This paper will pose two key questions: does hype affect marginalised communities, particularly hype around new technologies such as AI; and what impact does the LGBTQ + community experience as a result of hype. This paper will then move on to discuss areas that provide a focus for discourse of AI hype and the impact on the LGBTQ + community: policy and decision-making, the maintenance of the cisgender heteronormative (cishet) baseline, the ubiquity of a mythology of AI, and the role of market expansion.
Ecotoxicological assessment of metformin as an antidiabetic water residue treated by electron beam accelerator irradiation
Authors: Tominaga Flávio Kiyoshi , de Jesus Juliana Mendonça Silva , Klanovicz Natalia , Redígolo Marcelo Miyada , Silva Thalita Tieko , Lebre Daniel Temponi , Teixeira Antonio Carlos Silva Costa , Leo Patricia , Borrely Sueli Ivone
Published: February 2024

Metformin (MET), an antidiabetic compound, has received increasing attention, as it cannot be effectively removed during conventional wastewater treatment processes and may act as an endocrine disruptor. Electron beam irradiation (EBI) is an eco-friendly process able to degrade and neutralize biohazardous pollution almost instantly. In this context, this study applied EBI to MET degradation and detoxification in aqueous solutions. A 98% MET degradation rate and TOC removal of 19.04 ± 1.20% at a 1.0 kGy EBI dose was obtained, with up to 65% mineralization reached at 5.0 kGy. Toxicity assays were performed with Vibrio fischeri, Saccharomyces cerevisiae, and Daphnia similis, and the findings indicate that generated byproducts were only more toxic to D. similis. This reveals the need to assess organisms belonging to different trophic levels. A cytotoxic assessment employing Allium cepa roots demonstrated no toxic effects concerning untreated and irradiated samples.
A Lightweight Model for Malicious Code Classification Based on Structural Reparameterisation and Large Convolutional Kernels
Authors: Li Sicong , Wang Jian , Song Yafei , Wang Shuo , Wang Yanan
Published: February 2024

With the advancement of adversarial techniques for malicious code, malevolent attackers have propagated numerous malicious code variants through shell coding and code obfuscation. Addressing the current issues of insufficient accuracy and efficiency in malicious code classification methods based on deep learning, this paper introduces a detection strategy for malicious code, uniting Convolutional Neural Networks (CNNs) and Transformers. This approach utilizes deep neural architecture, incorporating a novel fusion module to reparametrize the structure, which mitigates memory access costs by eliminating residual connections within the network. Simultaneously, overparametrization during linear training time and significant kernel convolution techniques are employed to enhance network precision. In the data preprocessing stage, a pixel-based image size normalization algorithm and data augmentation techniques are utilized to remedy the loss of texture information in the malicious code image scaling process and class imbalance in the dataset, thereby enhancing essential feature expression and alleviating model overfitting. Empirical evidence substantiates this method has improved accuracy and the most recent malicious code detection technologies.
Interpretable Tongue Constitution Recognition via Reshaped Wavelet Attention
Authors: Wen Guihua , Liang Haozan , Li Huihui , Wen Pengcheng , Chen Rui , Li Cheng
Published: February 2024

Currently deep neural networks have been used to perform the tongue constitution recognition, but they are still challenged, failing to extract nice multi-scale and multi-level features. This paper proposes a novel interpretable tongue constitution recognition method based on the reshaped wavelet attention. It separates multi-scale features through discrete wavelet transform and then uses the attention mechanism to weight them. Subsequently, these features are reshaped to the high-dimensional space where the association knowledge of multi-level features are mined and hierarchized so as to fuse them efficiently. Finally, both are integrated into the framework of convolution neural network to generate the more accurate tongue image attributes, by which the tongue constitution recognition is performed. The proposed method not only obtains the higher performance with small cost, but also nicely interprets them. Experimental results show that the proposed method is effective, efficient, and interpretable.
“We forgot about the donkeys!” An institutional analysis of the shift in animal welfare from direct implementation towards advocacy-based programming
Authors: Haddy Emily , Proops Leanne , Burden Faith , Raw Zoe , Kaminski Juliane , Brown Julia
Published: February 2024

Shifts from direct implementation to advocacy-based programming have been documented across many non-governmental organisation (NGO) sectors, including animal welfare. Semi-structured interviews with 32 staff from different positions within animal welfare NGOs explored recent programming changes. Maintaining a balance between direct implementation and advocacy-based activities emerged as a strong theme. The findings suggest that risks are associated with both the direct implementation status quo and transitioning to an advocacy-based focus. Risks of the former include treating symptoms rather than root causes of welfare problems. Organisational change can be disruptive and necessitates realignment of core competences, in turn influencing NGO mission. Identified risks of transition include loss of individuals whose values fail to align with new programming directions, increased upwards accountability requirements for accessing institutional donors and difficulties when phasing out direct implementation approaches. Whilst having to be dynamic, NGOs need to evaluate the risks associated with programming decisions, considering their vision, mission and staff identity in order to ensure that welfare programming is as effective as possible.
Utilization of system models in model-based systems engineering: definition, classes and research directions based on a systematic literature review
Authors: Wilking Fabian , Horber Dennis , Goetz Stefan , Wartzack Sandro
Published: February 2024

The use of system models within model-based systems engineering (MBSE) is essential for improved communication or system documentation. Previous publications have investigated further reuse of these system models, for example, transforming them directly into discipline-specific models for reuse. The authors refer to this as the term “Utilization” of system models. It aims the compensation of modelling efforts and a further integration of linked models within MBSE. Motivated by a lack of common understanding of this term, a systematic literature review of the state of the art is presented. With this systematic overview, a definition and classification system for different use cases and system life cycle stages are created. These are key results to support engineers and researchers in adopting existing or discovering new utilization approaches. This supports the mission of advanced systems engineering and aims the identification of new research directions coming along with SysML v2 and the advanced systems engineering methods.
Implementation of contact precautions for multidrug-resistant organisms in the post–COVID-19 pandemic era: An updated national Emerging Infections Network (EIN) survey
Authors: Howard-Anderson Jessica R. , Gottlieb Lindsey B. , Beekmann Susan E. , Polgreen Philip M. , Jacob Jesse T. , Uslan Daniel Z.
Published: February 2024

Objective:

To understand how healthcare facilities employ contact precautions for patients with multidrug-resistant organisms (MDROs) in the post–coronavirus disease 2019 (COVID-19) era and explore changes since 2014.

Design:

Cross-sectional survey.

Participants:

Emerging Infections Network (EIN) physicians involved in infection prevention or hospital epidemiology.

Methods:

In September 2022, we sent via email an 8-question survey on contact precautions and adjunctive measures to reduce MDRO transmission in inpatient facilities. We also asked about changes since the COVID-19 pandemic. We used descriptive statistics to summarize data and compared results to a similar survey administered in 2014.

Results:

Of 708 EIN members, 283 (40%) responded to the survey and 201 reported working in infection prevention. A majority of facilities (66% and 69%) routinely use contact precautions for methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) respectively, compared to 93% and 92% in 2014. Nearly all (>90%) use contact precautions for Candida auris, carbapenem-resistant Enterobacterales (CRE), and carbapenem-resistant Acinetobacter baumannii. More variability was reported for carbapenem-resistant Pseudomonas aeruginosa and extended-spectrum β-lactamase–producing gram-negative organisms. Compared to 2014, fewer hospitals perform active surveillance for MRSA and VRE. Overall, 90% of facilities used chlorhexidine gluconate bathing in all or select inpatients, and 53% used ultraviolet light or hydrogen peroxide vapor disinfection at discharge. Many respondents (44%) reported changes to contact precautions since COVID-19 that remain in place.

Conclusions:

Heterogeneity exists in the use of transmission-based precautions and adjunctive infection prevention measures aimed at reducing MDRO transmission. This variation reflects a need for updated and specific guidance, as well as further research on the use of contact precautions in healthcare facilities.
Incidence and transmission associated with respiratory viruses in an acute care facility: An observational study
Authors: Valek Abby L. , Srinivasa Vatsala Rangachar , Ayres Ashley M. , Cheung Steven , Harrison Lee H. , Snyder Graham M.
Published: February 2024

We estimated the extent of respiratory virus transmission over three pre-COVID-19 seasons. Of 16,273 assays, 22.9% (3,726) detected ≥1 respiratory virus. The frequency of putatively hospital-acquired infection ranged from 6.9% (influenza A/B) to 24.7% (adenovirus). The 176 clusters were most commonly associated with rhinovirus/enterovirus (70) and influenza A/B (62).
SAMPLE SELECTION, CHARACTERIZATION AND CHOICE OF TREATMENT FOR ACCURATE RADIOCARBON ANALYSIS—INSIGHTS FROM THE ETH LABORATORY
Authors: Hajdas Irka , Guidobaldi Giulia , Haghipour Negar , Wyss Karin
Published: February 2024

Accurate radiocarbon (14C) analysis depends on a successful carbon separation relevant to the studied object. The process of 14C dating involves the following steps: characterization and sample choice, sample treatment, measurements, and evaluation of the results. Here, we provide an overview of conventional approaches to macromolecular samples and address specific issues such as detecting and removing contamination with roots, dolomite, and conservation products. We discuss the application of elemental analysis (%N, %C) in the preparation of bones and the infrared analysis in monitoring the contamination of samples. Our observations provide the basis for the discussions of the existing results and for planning the future sampling.
14C MEASUREMENT OF SAMPLES FOR ENVIRONMENTAL SCIENCE APPLICATIONS AT THE NATIONAL ENVIRONMENTAL ISOTOPE FACILITY (NEIF) RADIOCARBON LABORATORY, SUERC, UK
Authors: Ascough P , Bompard N , Garnett M H , Gulliver P , Murray C , Newton J-A , Taylor C
Published: February 2024

The National Environmental Isotope Facility (NEIF) Radiocarbon Laboratory at the Scottish Universities Environmental Research Centre (SUERC) performs radiocarbon measurement of a wide range of sample matrices for applications in environmental research. Radiocarbon is applied to palaeoenvironmental, palaeoceanographic, and palaeoclimatic investigations, as well as work to understand the source, fate, turnover, and age of carbon in the modern carbon cycle. The NEIF Radiocarbon Laboratory supports users in the development and deployment of novel sampling techniques and laboratory approaches. Here, we give an overview of methods and procedures used by the laboratory to support the field collection, laboratory processing, and measurement of samples. This includes in-house development of novel and/or specialized methods and approaches, such as field collection of CO2 and CH4, hydropyrolysis, and ramped oxidation. The sample types covered include organic remains (e.g., plant material, peat, wood, charcoal, proteins), carbonates (e.g., speleothems, foraminifera, mollusc shell, travertine), waters (dissolved organic and inorganic carbon), gases (CO2 and CH4), soils and sediments (including sub-fractions).
A randomized controlled trial of a digital cognitive-behavioral therapy program (COMPASS) for managing depression and anxiety related to living with a long-term physical health condition
Authors: Picariello Federica , Hulme Katrin , Seaton Natasha , Hudson Joanna L , Norton Sam , Wroe Abigail , Moss-Morris Rona
Published: February 2024

Background

To evaluate the clinical efficacy of COMPASS, a therapist-supported digital therapeutic for reducing psychological distress (anxiety/depression) in people living with long-term physical health conditions (LTCs).

Methods

A two-armed randomized-controlled trial recruiting from LTC charities. Participants with anxiety and/or depression symptoms related to their LTC(s) were randomized (concealed allocation via independent administrator) to COMPASS (access to 11 tailored modules plus five thirty-minute therapist support sessions) or standard charity support (SCS). Assessments were completed online pre-randomization, at 6- and 12-weeks post-randomization. Primary outcome was Patient Health Questionnaire Anxiety and Depression Scale; PHQ-ADS measured at 12-weeks. Analysis used intention-to-treat principles with adjusted mean differences estimated using linear mixed-effects models. Data-analyst was blinded to group allocation.

Results

194 participants were randomized to COMPASS (N = 94) or SCS (N = 100). At 12-weeks, mean level of psychological distress was 6.82 (95% confidence interval; CI 4.55–9.10) points lower (p < 0.001) in the COMPASS arm compared with SCS (standardized mean difference of 0.71 (95% CI 0.48–0.95)). The COMPASS arm also showed moderate significant treatment effects on secondary outcomes including depression, anxiety and illness-related distress and small significant effects on functioning and quality-of-life. Rates of adverse events were comparable across the arms. Deterioration in distress at 12-weeks was observed in 2.2% of the SCS arm, and no participants in the COMPASS arm.

Conclusion

Compared with SCS, COMPASS digital therapeutic with minimal therapist input reduces psychological distress at post-treatment (12-weeks). COMPASS offers a potentially scalable implementation model for health services but its translation to these contexts needs further evaluating.

Trial Registration

NCT04535778
Old Patronage during the New Deal: Did Urban Machines Use Work Relief Programs to Benefit the National Democratic Party?
Authors: Ternullo Stephanie , Shachter Simon Y.
Published: February 2024

What role did urban machines play in national politics during the New Deal? To what extent did they serve as facilitators in a local-national patronage system, converting the flow of federal funds into their cities into votes for federal Democratic candidates? To answer these questions, we bring together data on urban machines and work relief spending, the New Deal programs that received the most public and political scorn for their supposed patronage uses. Despite long-standing claims that Franklin D. Roosevelt and other New Dealers funneled extra work relief funds to urban machines, and that machines converted those funds into votes for the national Democratic Party, we find little evidence of this exchange relationship. Machines did not receive a disproportionate share of work relief funds, but they did see large influxes of federal funds, just like other cities with high levels of economic need. And yet, based on two-way fixed effects models and synthetic control analyses, we find no evidence that they succeeded at using those funds to turn out votes for President Roosevelt. We find evidence for just one dimension of a local-national patronage system: Democratic Senate candidates did see larger increases in vote share in machine counties versus non-machine counties with similar increases in work relief expenditures.
A review of records and research actions for the poorly known Vanuatu Petrel Pterodroma [cervicalis] occulta
Authors: Vaughan Peter M. , Bird Jeremy P. , Bretagnolle Vincent , Shirihai Hadoram , Tennyson Alan J. D. , Miskelly Colin M. , Clarke Rohan H.
Published: February 2024

Gadfly petrels Pterodroma spp. are among the most threatened bird taxa. Conservation interventions have been successfully developed and applied for some gadfly petrel species, but a substantial gap remains in conservation science for this group in the tropical Pacific Ocean. The Vanuatu Petrel Pterodroma [cervicalis] occulta is an ideal exemplar to develop a pipeline for conservation science in tropical Pacific gadfly petrels as it is subject to many of the challenges facing other gadfly petrel taxa in the region. We review over 40 pelagic Vanuatu Petrel records and five research expeditions to the only known colony on the island of Vanua Lava, Vanuatu. These records provide a baseline from which to recommend conservation research actions for the taxon. The population status, taxonomy, distribution, and threat profile of the taxon are all poorly known, and these areas are high priorities for future research.
Managed competition in Aotearoa New Zealand: past experiences and future prospects
Authors: Cumming Jacqueline
Published: February 2024

This paper considers whether and how managed competition arrangements could be introduced into the Aotearoa health and disability system. The paper describes the key features of the system, including new organisational arrangements established from 1 July 2022. It discusses major reforms and managed competition plans that were developed in the 1990s, with the managed competition plans abandoned fairly early on, as a result of major issues with the reforms that had been implemented and with problems in designing a fair payment system for competing health plans. The paper goes on to argue that the development of capitated, risk-bearing and competing Primary Health Organisations set up in the 2000s should be considered in terms of managed competition, and the paper points to the issues that have arisen in Aotearoa due to a lack of regulations that would have better supported the better achievement of effectiveness, efficiency, and equity goals over the past 20 years. Finally, the paper also looks ahead to whether and how managed competition might again be considered in Aotearoa and the extent to which the system currently includes key pre-conditions to support such arrangements.
Design of dual-band tunable bandpass filter with constant absolute bandwidth based on triple transmission path
Authors: Guo Jing , Qian Lirong , Wang Litian , Li Cuiping , Tian Yahui , Li Honglang
Published: February 2024

In this paper, a novel tunable dual-band bandpass filter (BPF) with independently controlled passbands and constant absolute bandwidth (CABW) is proposed. The CABW passbands of designed dual-band BPF are obtained using manageable electric and magnetic mix coupling. Furthermore, the multiple transmission paths from the input port to the output port are extended for extra transmission zeros, which results in modified selectivity of the proposed dual-band BPF. The tunability and switchability of the developed filter can be implemented by introducing a single bias voltage of varactors for each band. For the tunable dual-band BPF, the simulated results show that the center frequency (CF) of the first passband varies from 2.38 to 2.68 GHz, and the CF of the second passband varies from 3.28 to 3.88 GHz, while 3-dB absolute bandwidths are 101 ± 7 MHz and 98 ± 4 MHz, respectively. Moreover, the two passbands of the filter can also be independently switched by removing the voltage imposed on the varactor CV1 and CV2. The measured results agree well with simulated results, which verify the design theory.
Minimal Impact of Late‐Season Melt Events on Greenland Ice Sheet Annual Motion
Authors: Ing Ryan N. , Nienow Peter W. , Sole Andrew J. , Tedstone Andrew J. , Mankoff Kenneth D.
Published: February 2024

Extreme melt and rainfall events can induce temporary acceleration of Greenland Ice Sheet motion, leading to increased advection of ice to lower elevations where melt rates are higher. In a warmer climate, these events are likely to become more frequent. In September 2022, seasonally unprecedented air temperatures caused multiple melt events over the Greenland Ice Sheet, generating the highest melt rates of the year. The scale and timing of the largest event overwhelmed the subglacial drainage system, enhancing basal sliding and increasing ice velocities by up to ∼240% relative to pre‐event velocities. However, ice motion returned rapidly to pre‐event levels, and the speed‐ups caused a regional increase in annual ice discharge of only ∼2% compared to when the effects of the speed‐ups were excluded. Therefore, although late melt‐season events are forecast to become more frequent and drive significant runoff, their impact on net mass loss via ice discharge is minimal.
The Measured Impact of Wildfires on Ozone in Western Canada From 2001 to 2019
Authors: Schneider Stephanie R. , Shi Buai , Abbatt Jonathan P. D.
Published: February 2024

The impacts on atmospheric ozone (O3) due to wildfires are difficult to characterize due to the many factors that affect O3's formation rate and the episodic nature of fire events. This study uses a very large set of air quality data (518,987 6‐hr data points) collected in Western Canada from 2001 to 2019 to determine the prevalence and severity of fire‐driven increases to measured O3 values. Wildfire events are identified using the automated Trajectory‐Fire Interception Method (TFIM), looking for interceptions between HYSPLIT back‐trajectories and wildfire hotspots. As with other studies, which have used more restricted sets of measurements, the results from this large‐scale, data‐driven approach indicate increases in the O3 mixing ratio with wildfire impact, on average ∼2 ppbv across all wildfire time periods. To understand the factors which lead to the largest increases, and to better compare to other studies looking at individual fire events, wildfire events are classified using their distance from the air quality measurement location, time of measurement, and corresponding PM2.5 value. Increases to O3 are largest during the daytime, when fires occur close to the air quality measurement, and with corresponding measurements of PM2.5 > 25 μg/m3. When an upper‐limit correction for the bias in UV photometric detection of ozone with MnCl2 scrubbers is applied, the analysis still yields a persistent increase in O3 during wildfires except for the highest PM2.5 levels. However, a more accurate correction to the potential bias is needed to fully understand the magnitude of the impact of wildfires on O3.
Institutional Dynamics Impact the Response of Urban Socio‐Hydrologic Systems to Supply Challenges
Authors: Wiechman Adam , Alonso Vicario Sara , Anderies John M. , Garcia Margaret , Azizi Koorosh , Hornberger George
Published: February 2024

Designing urban water systems to respond to the accelerating and unpredictable changes of the Anthropocene will require changes not only to built infrastructure and operating rules, but also to the governance arrangements responsible for investing in them. Yet, inclusion of this political‐economic feedback in dynamic models of infrastructure systems and socio‐hydrology has lagged behind operational feedback concerns. We address this gap through a dynamical systems application of the Coupled Infrastructure Systems (CIS) Framework, which provides the conceptual building blocks for analyzing social‐ecological systems through various classes of infrastructure and the flows of material and information among them. In the model, political‐economic feedback involves three decisions—infrastructure investment, rate‐setting, and short‐term demand curtailment—and each decision is constrained by institutional friction, the aggregation of decision and transaction costs associated with taking action. We apply the model to three cities in the Phoenix Metropolitan Area to compare how institutional friction interacts with a city's water resource portfolio and financial position to determine its sensitivity, or the degree to which its performance (e.g., providing sufficient supply to meet demand) changes given reductions in Colorado River water availability. We find that the slowing effect of institutional friction on investment and rate‐setting decisions can increase the sensitivity of a city's supply, but it can also promote objectives that compete with over‐response (e.g., rate burden). The effect is dependent on the initial operating capacity of the CIS and flexibility within the institutions, highlighting the need to consider political‐economic and operational feedback together when evaluating infrastructure systems.
SARS-CoV-2 spike protein-ACE2 interaction increases carbohydrate sulfotransferases and reduces N-acetylgalactosamine-4-sulfatase by p38 MAPK
Authors: Bhattacharyya Sumit , Tobacman Joanne K.
Published: February 2024

Immunostaining in lungs of patients who died with COVID-19 infection showed increased intensity and distribution of chondroitin sulfate and decline in N-acetylgalactostamine-4-sulfatase (Arylsulfatase B; ARSB). To explain these findings, human small airway epithelial cells were exposed to the SARS-CoV-2 spike protein receptor binding domain (SPRBD) and transcriptional mechanisms were investigated. Phospho-p38 MAPK and phospho-SMAD3 increased following exposure to the SPRBD, and their inhibition suppressed the promoter activation of the carbohydrate sulfotransferases CHST15 and CHST11, which contributed to chondroitin sulfate biosynthesis. Decline in ARSB was mediated by phospho-38 MAPK-induced N-terminal Rb phosphorylation and an associated increase in Rb-E2F1 binding and decline in E2F1 binding to the ARSB promoter. The increases in chondroitin sulfotransferases were inhibited when treated with phospho-p38-MAPK inhibitors, SMAD3 (SIS3) inhibitors, as well as antihistamine desloratadine and antibiotic monensin. In the mouse model of carrageenan-induced systemic inflammation, increases in phospho-p38 MAPK and expression of CHST15 and CHST11 and declines in DNA-E2F binding and ARSB expression occurred in the lung, similar to the observed effects in this SPRBD model of COVID-19 infection. Since accumulation of chondroitin sulfates is associated with fibrotic lung conditions and diffuse alveolar damage, increased attention to p38-MAPK inhibition may be beneficial in ameliorating Covid-19 infections.
Docking protein 6 (DOK6) selectively docks the neurotrophic signaling transduction to restrain peripheral neuropathy
Authors: Guo Yan , Xiang Pan , Sun Xiaojiao , Liu Wei , Zhou Jiafeng , Yin Bin , Hou Lin , Qiang Boqin , Li Huiliang , Shu Pengcheng , Peng Xiaozhong
Published: February 2024

The appropriate and specific response of nerve cells to various external cues is essential for the establishment and maintenance of neural circuits, and this process requires the proper recruitment of adaptor molecules to selectively activate downstream pathways. Here, we identified that DOK6, a member of the Dok (downstream of tyrosine kinases) family, is required for the maintenance of peripheral axons, and that loss of Dok6 can cause typical peripheral neuropathy symptoms in mice, manifested as impaired sensory, abnormal posture, paw deformities, blocked nerve conduction, and dysmyelination. Furthermore, Dok6 is highly expressed in peripheral neurons but not in Schwann cells, and genetic deletion of Dok6 in peripheral neurons led to typical peripheral myelin outfolding, axon destruction, and hindered retrograde axonal transport. Specifically, DOK6 acts as an adaptor protein for selectivity-mediated neurotrophic signal transduction and retrograde transport for TrkC and Ret but not for TrkA and TrkB. DOK6 interacts with certain proteins in the trafficking machinery and controls their phosphorylation, including MAP1B, Tau and Dynein for axonal transport, and specifically activates the downstream ERK1/2 kinase pathway to maintain axonal survival and homeostasis. This finding provides new clues to potential insights into the pathogenesis and treatment of hereditary peripheral neuropathies and other degenerative diseases.
Aptamers targeting SARS-CoV-2 nucleocapsid protein exhibit potential anti pan-coronavirus activity
Authors: Yang Minghui , Li Chunhui , Ye Guoguo , Shen Chenguang , Shi Huiping , Zhong Liping , Tian Yuxin , Zhao Mengyuan , Wu Pengfei , Hussain Abid , Zhang Tian , Yang Haiyin , Yang Jun , Weng Yuhua , Liu Xinyue , Wang Zhimin , Gan Lu , Zhang Qianyu , Liu Yingxia , Yang Ge , Huang Yuanyu , Zhao Yongxiang
Published: February 2024

Emerging and recurrent infectious diseases caused by human coronaviruses (HCoVs) continue to pose a significant threat to global public health security. In light of this ongoing threat, the development of a broad-spectrum drug to combat HCoVs is an urgently priority. Herein, we report a series of anti-pan-coronavirus ssDNA aptamers screened using Systematic Evolution of Ligands by Exponential Enrichment (SELEX). These aptamers have nanomolar affinity with the nucleocapsid protein (NP) of Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and also show excellent binding efficiency to the N proteins of both SARS, MERS, HCoV-OC43 and -NL63 with affinity KD values of 1.31 to 135.36 nM. Such aptamer-based therapeutics exhibited potent antiviral activity against both the authentic SARS-CoV-2 prototype strain and the Omicron variant (BA.5) with EC50 values at 2.00 nM and 41.08 nM, respectively. The protein docking analysis also evidenced that these aptamers exhibit strong affinities for N proteins of pan-coronavirus and other HCoVs (−229E and -HKU1). In conclusion, we have identified six aptamers with a high pan-coronavirus antiviral activity, which could potentially serve as an effective strategy for preventing infections by unknown coronaviruses and addressing the ongoing global health threat.
Asialoglycoprotein receptor 1 promotes SARS-CoV-2 infection of human normal hepatocytes
Authors: Yang Xinyi , Zheng Xu , Zhu Yuqi , Zhao Xiaying , Liu Jun , Xun Jiangna , Yuan Songhua , Chen Jun , Pan Hanyu , Yang Jinlong , Wang Jing , Liang Zhimin , Shen Xiaoting , Liang Yue , Lin Qinru , Liang Huitong , Li Min , Peng Fei , Lu Daru , Xu Jianqing , Lu Hongzhou , Jiang Shibo , Zhao Ping , Zhu Huanzhang
Published: February 2024

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes multi-organ damage, which includes hepatic dysfunction, as observed in over 50% of COVID-19 patients. Angiotensin I converting enzyme (peptidyl-dipeptidase A) 2 (ACE2) is the primary receptor for SARS-CoV-2 entry into host cells, and studies have shown the presence of intracellular virus particles in human hepatocytes that express ACE2, but at extremely low levels. Consequently, we asked if hepatocytes might express receptors other than ACE2 capable of promoting the entry of SARS-CoV-2 into cells. To address this question, we performed a genome-wide CRISPR-Cas9 activation library screening and found that Asialoglycoprotein receptor 1 (ASGR1) promoted SARS-CoV-2 pseudovirus infection of HeLa cells. In Huh-7 cells, simultaneous knockout ofACE2andASGR1prevented SARS-CoV-2 pseudovirus infection. In the immortalized THLE-2 hepatocyte cell line and primary hepatic parenchymal cells, both of which barely expressed ACE2, SARS-CoV-2 pseudovirus could successfully establish an infection. However, after treatment with ASGR1 antibody or siRNA targeting ASGR1, the infection rate significantly dropped, suggesting that SARS-CoV-2 pseudovirus infects hepatic parenchymal cells mainly through an ASGR1-dependent mechanism. We confirmed that ASGR1 could interact with Spike protein, which depends on receptor binding domain (RBD) and N-terminal domain (NTD). Finally, we also used Immunohistochemistry and electron microscopy to verify that SARS-CoV-2 could infect primary hepatic parenchymal cells. After inhibiting ASGR1 in primary hepatic parenchymal cells by siRNA, the infection efficiency of the live virus decreased significantly. Collectively, these findings indicate that ASGR1 is a candidate receptor for SARS-CoV-2 that promotes infection of hepatic parenchymal cells.
IGF2BP3 enhances lipid metabolism in cervical cancer by upregulating the expression of SCD
Authors: Han Chenying , Hu Chenchen , Liu Tianyue , Sun Yuanjie , Hu Feiming , He Yuanli , Zhang Jiaxing , Chen Jiaxi , Ding Jiaqi , Fan Jiangjiang , Zhang Xiyang , Wang Jing , Qiao Xupeng , Jiang Dongbo , Yang Kun , Yang Shuya
Published: February 2024

Cervical cancer (CC) is the most common gynecologic malignancy, which seriously threatens the health of women. Lipid metabolism is necessary for tumor proliferation and metastasis. However, the molecular mechanism of the relationship between CC and lipid metabolism remains poorly defined. We revealed the expression of IGF2BP3 in CC exceeded adjacent tissues, and was positively associated with tumor stage using human CC tissue microarrays. The Cell Counting Kit-8, colony formation assay, 5-ethynyl-2′-deoxyuridine assay, transwell assays, wound-healing assays, and flow cytometry assessed the role of IGF2BP3 in proliferation and metastasis of CC cells. Besides, exploring the molecular mechanism participating in IGF2BP3-driven lipid metabolism used RNA-seq, which determined SCD as the target of IGF2BP3. Further, lipid droplets, cellular triglyceride (TG) contents, and fatty acids were accessed to discover that IGF2BP3 can enhance lipid metabolism in CC. Moreover, RIP assay and methylated RNA immunoprecipitation experiments seeked the aimed-gene-binding specificity. Lastly, the IGF2BP3 knockdown restrained CC growth and lipid metabolism, after which SCD overexpression rescued the influence in vitro and in vivo using nude mouse tumor-bearing model. Mechanistically, IGF2BP3 regulated SCD mRNA m6A modifications via IGF2BP3-METTL14 complex, thereby enhanced CC proliferation, metastasis, and lipid metabolism. Our study highlights IGF2BP3 plays a crucial role in CC progression and represents a therapeutic latent strategy. It is a potential tactic that blocks the metabolic pathway relevant to IGF2BP3 with the purpose of treating CC.
Innate and adaptive immune cell interaction drives inflammasome activation and hepatocyte apoptosis in murine liver injury from immune checkpoint inhibitors
Authors: Shojaie Layla , Bogdanov Jacob M. , Alavifard Helia , Mohamed Mahmoud G. , Baktash Aria , Ali Myra , Mahov Simeon , Murray Sue , Kanel Gary C. , Liu Zhang-Xu , Ito Fumito , In Gino K. , Merchant Akil , Stohl William , Dara Lily
Published: February 2024

Immune checkpoints (CTLA4 & PD-1) are inhibitory pathways that block aberrant immune activity and maintain self-tolerance. Tumors co-opt these checkpoints to avoid immune destruction. Immune checkpoint inhibitors (ICIs) activate immune cells and restore their tumoricidal potential, making them highly efficacious cancer therapies. However, immunotolerant organs such as the liver depend on these tolerogenic mechanisms, and their disruption with ICI use can trigger the unintended side effect of hepatotoxicity termed immune-mediated liver injury from ICIs (ILICI). Learning how to uncouple ILICI from ICI anti-tumor activity is of paramount clinical importance. We developed a murine model to recapitulate human ILICI using CTLA4+/- mice treated with either combined anti-CTLA4 + anti-PDL1 or IgG1 + IgG2. We tested two forms of antisense oligonucleotides to knockdown caspase-3 in a total liver (parenchymal and non-parenchymal cells) or in a hepatocyte-specific manner. We also employed imaging mass cytometry (IMC), a powerful multiplex modality for immunophenotyping and cell interaction analysis in our model. ICI-treated mice had significant evidence of liver injury. We detected cleaved caspase-3 (cC3), indicating apoptosis was occurring, as well as Nod-like receptor protein 3 (NLRP3) inflammasome activation, but no necroptosis. Total liver knockdown of caspase-3 worsened liver injury, and induced further inflammasome activation, and Gasdermin-D-mediated pyroptosis. Hepatocyte-specific knockdown of caspase-3 reduced liver injury and NLRP3 inflammasome activation. IMC-generated single-cell data for 77,692 cells was used to identify 22 unique phenotypic clusters. Spatial analysis revealed that cC3+ hepatocytes had significantly closer interactions with macrophages, Kupffer cells, and NLRP3hi myeloid cells than other cell types. We also observed zones of three-way interaction between cC3+ hepatocytes, CD8 + T-cells, and macrophages. Our work is the first to identify hepatocyte apoptosis and NLRP3 inflammasome activation as drivers of ILICI. Furthermore, we report that the interplay between adaptive and innate immune cells is critical to hepatocyte apoptosis and ILICI.
Cardiac cell senescence: molecular mechanisms, key proteins and therapeutic targets
Authors: Luan Yi , Zhu Xiaofan , Jiao Yuxue , Liu Hui , Huang Zhen , Pei Jinyan , Xu Yawei , Yang Yang , Ren Kaidi
Published: February 2024

Cardiac aging, particularly cardiac cell senescence, is a natural process that occurs as we age. Heart function gradually declines in old age, leading to continuous heart failure, even in people without a prior history of heart disease. To address this issue and improve cardiac cell function, it is crucial to investigate the molecular mechanisms underlying cardiac senescence. This review summarizes the main mechanisms and key proteins involved in cardiac cell senescence. This review further discusses the molecular modulators of cellular senescence in aging hearts. Furthermore, the discussion will encompass comprehensive descriptions of the key drugs, modes of action and potential targets for intervention in cardiac senescence. By offering a fresh perspective and comprehensive insights into the molecular mechanisms of cardiac senescence, this review seeks to provide a fresh perspective and important theoretical foundations for the development of drugs targeting this condition.
ROS/MMP-9 mediated CS degradation in BMSC inhibits citric acid metabolism participating in the dual regulation of bone remodelling
Authors: Da Wacili , Jiang Wen , Tao Lin
Published: February 2024

It is necessary to figure out the abnormal energy metabolites at the cellular level of postmenopausal osteoporosis (PMOP) bone microenvironment. In this study, we constructed PMOP model by ovariectomy and identified 9 differential metabolites compared with control femur by energy metabolomic. The enrichment analysis of differential metabolites revealed that tricarboxylic acid cycle, glucagon pathway and purinergic signaling pathway were the main abnormal metabolic processes. Citric acid was identified as the key metabolite by constructing compound reaction–enzyme–gene network. The functional annotation of citric acid targets identified by network pharmacological tools indicated that matrix metalloproteinase 9 (MMP-9) may be involved in regulating citric acid metabolism in the osteogenic differentiation of bone marrow mesenchymal stem cell (BMSC). Molecular docking shows that the interaction forces between MMP-9 and citric acid synthase (CS) is −638, and there are multiple groups of residues used to form hydrogen bonds. Exogenous H2O2 promotes the expression of MMP-9 in BMSC to further degrade CS resulting in a decrease in mitochondrial citric acid synthesis, which leads to the disorder of bone remodeling by two underlying mechanisms ((1) the decreased histone acetylation inhibits the osteogenic differentiation potential of BMSC; (2) the decreased bone mineralization by citric acid deposition). MMP-9-specific inhibitor (MMP-9-IN-1) could significantly improve the amount of CS in BMSC to promote cellular citric acid synthesis, and further enhance bone remodeling. These findings suggest inhibiting the degradation of CS by MMP-9 to promote the net production of citric acid in osteogenic differentiation of BMSC may be a new direction of PMOP research.
Biporous silica nanostructure-induced nanovortex in microfluidics for nucleic acid enrichment, isolation, and PCR-free detection
Authors: Jeon Eunyoung , Koo Bonhan , Kim Suyeon , Kim Jieun , Yu Yeonuk , Jang Hyowon , Lee Minju , Kim Sung-Han , Kang Taejoon , Kim Sang Kyung , Kwak Rhokyun , Shin Yong , Lee Joonseok
Published: February 2024

Efficient pathogen enrichment and nucleic acid isolation are critical for accurate and sensitive diagnosis of infectious diseases, especially those with low pathogen levels. Our study introduces a biporous silica nanofilms-embedded sample preparation chip for pathogen and nucleic acid enrichment/isolation. This chip features unique biporous nanostructures comprising large and small pore layers. Computational simulations confirm that these nanostructures enhance the surface area and promote the formation of nanovortex, resulting in improved capture efficiency. Notably, the chip demonstrates a 100-fold lower limit of detection compared to conventional methods used for nucleic acid detection. Clinical validations using patient samples corroborate the superior sensitivity of the chip when combined with the luminescence resonance energy transfer assay. The enhanced sample preparation efficiency of the chip, along with the facile and straightforward synthesis of the biporous nanostructures, offers a promising solution for polymer chain reaction-free detection of nucleic acids.
β-Variational autoencoders and transformers for reduced-order modelling of fluid flows
Authors: Solera-Rico Alberto , Sanmiguel Vila Carlos , Gómez-López Miguel , Wang Yuning , Almashjary Abdulrahman , Dawson Scott T. M. , Vinuesa Ricardo
Published: February 2024

Variational autoencoder architectures have the potential to develop reduced-order models for chaotic fluid flows. We propose a method for learning compact and near-orthogonal reduced-order models using a combination of aβ-variational autoencoder and a transformer, tested on numerical data from a two-dimensional viscous flow in both periodic and chaotic regimes. Theβ-variational autoencoder is trained to learn a compact latent representation of the flow velocity, and the transformer is trained to predict the temporal dynamics in latent-space. Using theβ-variational autoencoder to learn disentangled representations in latent-space, we obtain a more interpretable flow model with features that resemble those observed in the proper orthogonal decomposition, but with a more efficient representation. Using Poincaré maps, the results show that our method can capture the underlying dynamics of the flow outperforming other prediction models. The proposed method has potential applications in other fields such as weather forecasting, structural dynamics or biomedical engineering.
Operando investigation of the synergistic effect of electric field treatment and copper for bacteria inactivation
Authors: Jarin Mourin , Wang Ting , Xie Xing
Published: February 2024

As the overuse of chemicals in our disinfection processes becomes an ever-growing concern, alternative approaches to reduce and replace the usage of chemicals is warranted. Electric field treatment has shown promising potential to have synergistic effects with standard chemical-based methods as they both target the cell membrane specifically. In this study, we use a lab-on-a-chip device to understand, observe, and quantify the synergistic effect between electric field treatment and copper inactivation. Observations in situ, and at a single cell level, ensure us that the combined approach has an enhancement effect leading more bacteria to be weakened by electric field treatment and susceptible to inactivation by copper ion permeation. The synergistic effects of electric field treatment and copper can be visually concluded here, enabling the further study of this technology to optimally develop, mature, and scale for its various applications in the future.