bluuebunny/crossref_metadata_2025 huggingface dataset:
Aspect-based drug review classification through a hybrid model with ant colony optimization using deep learning
Authors: Durga Putta , Godavarthi Deepthi , Kant Shashi , Basa Santi Swarup
Published: July 2024

The task of aspect-level sentiment analysis is intricately designed to determine the sentiment polarity directed towards a specific target within a sentence. With the increasing availability of online reviews and the growing importance of healthcare decisions, analyzing drug reviews has become a critical task. Traditional sentiment analysis, which categorizes a whole review as positive, negative, or neutral, provides limited insights for consumers and healthcare professionals. Aspect-based sentiment analysis (ABSA) aims to overcome these limitations by identifying and evaluating the sentiment associated with specific aspects or attributes of drugs mentioned in the reviews. Various fields, including business, politics, and medicine, have been explored in the context of sentiment analysis. Automation of online user reviews allows pharmaceutical companies to assess large amounts of user feedback. This helps extract pharmacological efficacy and side effect insights. The data collected could improve pharmacovigilance. Reviewing user comments can provide valuable data that can be used to improve drug safety and efficacy monitoring procedures. This improves pharmacovigilance processes, improving pharmaceutical outcomes understanding and corporate decision-making. Therefore, we propose a pre-trained RoBERTa with a Bi-LSTM model to categorise drug reviews from online sources and pre-process the text data. Ant Colony Optimization can be used in feature selection for ABSA, helping to identify the most relevant aspects and sentiments. Further, RoBERTa is fine-tuned to perform ABSA on the dataset, enabling the system to categorize aspects and determine the associated sentiment. The outcomes reveal that the suggested framework has achieved higher accuracy (96.78%) and F1 score (98.29%) on druglib.com, and 95.02% on the drugs.com dataset, than several prior state-of-the-art methods.
Beyond Reasonableness: Argumentative Virtues in Pragma-Dialectics
Authors: Gascón José Ángel
Published: July 2024

The pragma-dialectical research program begins with a philosophical estate, in which a conception of reasonableness is offered that must serve as ground for the theoretical estate. Pragma-dialectics has produced many important insights in the theoretical estate, including the ideal model and the rules for critical discussions. However, here I will argue that the conception of reasonableness that the pragma-dialecticians adopt in the philosophical estate, based on anti-dogmatism, assumption of fallibilism and willingness to engage in critical discussion, is too narrow to support the whole system of pragma-dialectical rules. What the philosophical estate requires is a broad and rich conception of excellent performance in argumentative practice, which then the rules of the critical discussion are intended to capture systematically in the theoretical estate. In my view, a virtue approach to argumentation is the ideal framework for such a philosophical ground. Virtues such as intellectual empathy, intellectual honesty, faith in reason, or recognition of reliable authority, point towards aspects of a philosophical conception of excellent arguing that are absent in the pragma-dialectical view of reasonableness. Finally, I will argue that what pragma-dialecticians call “second-order conditions” for a critical discussion are better understood as minimal argumentative virtue, a basic degree of virtue that arguers are required to possess in order to be prepared to participate in a fruitful critical discussion. The possession of such a basic degree of argumentative virtue is, I believe, what we mean when we characterise someone as reasonable.
Black swans swimming in product streams: method for including unplanned events in life cycle assessment
Authors: Hermansson Frida , Arvidsson Rickard , Svanström Magdalena
Published: July 2024

Introduction

Unplanned events such as accidents and more massive black-swan events are contingent to modern technology. However, varying approaches and inconsistent guidelines make the inclusion of unplanned events in life cycle assessment (LCA) uncommon and challenging. This paper discusses the relevance of considering unplanned events in LCA and shows how they can be included in LCA practice.

Method

A theoretical background to the concepts of black swans, accidents, and unplanned events is first provided. We then propose a method for how unplanned events can be included in LCA practice, illustrated through three cases: (i) a sabotage in the energy system, (ii) an accident in the use phase, and (iii) a sudden policy change.

Results

The results show that unplanned events can be included and may significantly affect LCA results, sometimes even fulfilling criteria for black-swan events.

Conclusions

We suggest that unplanned events should be included in LCA when relevant, e.g. as one scenario in LCAs of product systems sensitive to accidents. We also suggest that changes in flows due to unplanned events should be considered in unit processes, so that their impacts become distributed across downstream product systems depending on demand for the unit-process output.
A comparison of brown fat tissue related hormone levels in metabolically healthy and unhealthy individuals with obesity
Authors: Mutlu Hacer Hicran , Koç Ada Saniye , Uzunlulu Mehmet , Mutlu Hasan Hüseyin , Sargın Mehmet , Oğuz Aytekin
Published: July 2024

Purpose

One of the key functions of brown adipose tissue is its positive impact on metabolism. This study aimed to examine the potential involvement of brown fat-related hormones in the development of metabolically healthy obesity. Specifically, we sought to compare the levels of NRG4, FGF21, and irisin between metabolically healthy and unhealthy individuals with obesity.

Methods

Patients with BMI ≥ 30 kg/m2 and aged between 20 and 50 years were included in the study. Among these patients, those who did not have any metabolic syndrome criteria except for increased waist circumference were defined as metabolically healthy obese. Age, gender, BMI, body fat, and muscle mass, matched metabolically healthy and unhealthy obese groups were compared in terms of FGF21, irisin, and NRG4 levels.

Results

Metabolically healthy and unhealthy obese groups were similar in terms of age and gender. There was no difference between the two groups in terms of BMI, weight, total body fat, muscle, fat-free mass, distribution of body fat and muscle mass. No statistically significant difference was found between irisin, NRG4, and FGF21 levels between metabolically healthy and unhealthy individuals with obesity. It was found that irisin had a significant inverse correlation with BMI and body fat percentage.

Conclusion

The present study showed no difference between metabolically healthy and unhealthy obese individuals in terms of irisin, FGF21, and NRG4 levels. The weak association between irisin and BMI and body fat percentage may suggest a potential link between irisin with metabolic health.
Norwegian Health Professionals’ Attitudes Toward Addressing Sexual Health with People with Intellectual Disabilities
Authors: Devik Siri Andreassen , Henriksen Stine Marlen , Areskoug-Josefsson Kristina , Olsen Rose Mari
Published: July 2024

Introduction

Staff working with individuals with intellectual disabilities face challenges addressing sexual health. Professionals in this context have diverse backgrounds and education, and little is known about their attitudes and skills in providing support for a healthy sexual life and preventing abuse. Moreover, this topic has not been explored in the Norwegian context. The current study examined health professionals’ attitudes toward addressing sexual health with individuals with intellectual disabilities in Norwegian municipal health and care services.

Methods

A cross-sectional study was conducted using the Norwegian version of the professionals’ attitudes toward addressing sexual health among 72 health professionals working in municipal services for people with intellectual disabilities in Mid-Norway. The data was collected from November 2022 to January 2023.

Results

The professionals reported feeling partially comfortable and prepared to address sexual health issues with clients. They consistently expressed a need for more basic knowledge about sexual health and training in communicating about sexuality. Attitudes toward addressing sexual health varied based on the professionals’ education, gender, age, and work experience.

Conclusions

More targeted training on sexual health is needed within the educational programmes in health and social sciences. Sexual health should also be continuously addressed in the workplace and among colleagues. The differences in attitudes between professionals indicate that the composition of the staff benefits from diversity.

Policy Implications

Healthcare managers are responsible for ensuring greater openness and reflection on attitudes toward sexuality among individuals with intellectual disabilities in workplaces. Educational institutions must provide the necessary skill development and training in communication about sexual health for this client group.
Should We Discourage AI Extension? Epistemic Responsibility and AI
Authors: Naeem Hadeel , Hauser Julian
Published: July 2024

We might worry that our seamless reliance on AI systems makes us prone to adopting the strange errors that these systems commit. One proposed solution is to design AI systems so that they are not phenomenally transparent to their users. This stops cognitive extension and the automatic uptake of errors. Although we acknowledge that some aspects of AI extension are concerning, we can address these concerns without discouraging transparent employment altogether. First, we believe that the potential danger should be put into perspective – many unreliable technologies are unlikely to be used transparently precisely because they are unreliable. Second, even an agent who transparently employs a resource may reflect on its reliability. Finally, agents can rely on a process transparently and be yanked out of their transparent use when it turns problematic. When an agent is responsive to the reliability of their process in this way, they have epistemically integrated it, and the beliefs they form with it are formed responsibly. This prevents the agent from automatically incorporating problematic beliefs. Responsible (and transparent) use of AI resources – and consequently responsible AI extension – is hence possible. We end the paper with several design and policy recommendations that encourage epistemic integration of AI-involving belief-forming processes. Keywords: phenomenal transparency, artificial intelligence, cognitive extension, adversarial attack, cognitive integration.
Strategic Development of Ni–Cu–Fe2O3 Composite Coatings to Strengthen Mild Steel Against Corrosion
Authors: Krishnaraj P. , Navada Meghana K , Aroor Ganesha , Shetty Akshatha R
Published: July 2024

Mild steel is extensively employed in various industries due to its affordability and versatility. However, its susceptibility to corrosion poses a significant challenge. This study explores the efficacy of protecting mild steel by applying coatings composed of highly noble copper and its alloys. In this direction, Ni–Cu alloy and Ni–Cu–Fe2O3 coating have been developed from a sulfate citrate bath on mild steel through the electrodeposition method. The alloy and composite coating deposition was done at different current densities 1 A dm−2, 2 A dm−2, 3 A dm−2, and 4 A dm−2. The copper content of the coating has increased with an increase in current density in both alloy and composite coatings. The deposit with a high Copper content showed lower crystallite size with a lower corrosion rate value at a current density of 3 A dm−2. The trace addition of Fe2O3 into the Ni–Cu alloy matrix has improved the overall corrosion resistance of the mild steel materials as compared to bare Ni–Cu alloy coating.
Greener and Sustainable Production: Production of Industrial Zinc (II) Acetate Solution and Recovery of Some Metals (Zn, Pb, Ag) from Zinc Plant Residue by Ultrasound-Assisted Leaching
Authors: Sarı Zeynel Abidin
Published: July 2024

Zinc plant residue (ZPR) contains significant amounts of valuable metal (Zn, Pb, Ag, etc.) compounds, as well as various heavy metals and harmful compounds that pollute the environment. Processing such residues allows for the recovery and reuse of valuable metals, which is crucial for sustainable resource management. This study investigated a two-stage leaching process of Zn, Pb, and Ag recovery from ZPR. The first stage of ultrasonic-assisted leaching of ZPR was applied to produce an industrial selective zinc acetate solution. Leaching experiments were carried out with an ultrasonic device in the presence of acetic acid, known as organic acid. Under optimum leaching conditions, the extraction of Zn and Fe metals was obtained as 76.13% and 1.32% Fe, respectively. According to the Brunauer–Emmett–Teller (BET) analysis results on the original sample and ultrasonic leaching residue (ULR), the BET surface area and micropore area increased. However, the mean adsorption pore width decreased. In the second stage, conventional sodium chloride leaching was applied to recover lead and silver from the remaining solid after the first stage. Under the optimum conditions in this stage, 80.12% of Pb and 96.2% of Ag were extracted. The presence of coordination between Zn2+/AcO− (acetate) and Pb2+/Cl− complexes in the leaching solution was revealed by Raman spectroscopy. Finally, according to the characterization analysis of the final leaching residue, it was determined that iron oxides and silicate species accumulated in the solid. In conclusion, a significant reduction in the rate of pollution and toxic metals in ZPR was noticed.

Graphical Abstract
Effect of Expanded Glass Lightweight Aggregate on the Performance of Geopolymer Mortar at Elevated Temperatures
Authors: Al Mohammad Ahmad , ÇEVİK Abdulkadir , Jwaida Zahraa , Shubbar Ali
Published: July 2024

The greenhouse gas emissions associated with conventional concrete as a result of the cement industry have prompted scientists to search for eco-friendly alternatives. Among these promising alternatives is geopolymer concrete or mortar. This work studies the impact of using polyvinyl alcohol (PVA) fibers and lightweight expanded glass (EG) aggregate on the mechanical behaviour of lightweight geopolymer mortar (LWGM) at various temperatures (room temperature, 250 °C, and 500 °C). EG was utilized to partially replace the sand by 10 and 20%. Limited studies dealt with geopolymer mortar based on such composition at high temperatures. The geopolymer mortar was created using slag as the main precursor activated by a mixed solution of sodium hydroxide and sodium silicate. Various combinations were produced, and their behaviour was observed at room and high temperatures. Several tests such as workability, compressive and flexural strengths, density, stress-strain relationship, load-displacement behaviour, and uniaxial tensile strength were performed. The findings of the study indicate that the density and compressive strength of geopolymer mortar reduced with increasing the replacement level by the EG. However, the utilization of 10% EG can produce a lightweight mortar with a compressive strength of 17.9 at 28 days. Moreover, the use of 1% PVA significantly improves the mechanical performance. Furthermore, the mechanical characteristics of the materials were considerably altered when subjected to extreme temperatures of 500 °C as observed from experimental data.
Research-based learning as an innovative approach for teaching students of environmental engineering: a case study of the emerging field of microplastics in soil
Authors: Shah Tavseef Mairaj , Jannesarahmadi Sahar , Shokri-Kuehni Salome , Ellinger Dorothea , Brose Andrea , Or Dani , Shokri Nima
Published: July 2024

We implemented research-based learning (RBL) as an alternative to traditional frontal classroom lectures and laboratory sessions to impart knowledge on the emerging topic of microplastics in soil to students. The RBL module aimed at studying how microplastics (MPs) affect soil processes. We designed low-cost, small-scale and simple experiments for master’s students in Environmental Engineering at the Hamburg University of Technology. Students reported a clear understanding of concepts underlined by their presentation of the results and enthusiasm towards future exploration for their master’s or doctoral projects evidenced by a number of students carrying out research projects in the same field after finishing the module. The experiments were consequently published as an online learning module with the Hamburg Open Online University, to make them accessible for other students. The recent push in the education sector to include innovative teaching and learning methodologies offers new opportunities for RBL that are practical and replicable learning experiences that foster students’ research and problem-solving skills in areas of chemical, soil physics and environmental engineering fields.
Replication to first-year undergraduate students’ knowledge of academic misconduct
Authors: Locquiao Jed , Ives Bob
Published: July 2024

Student academic misconduct continues to vex higher education institutions in the United States and internationally. The COVID pandemic learning environment yielded more rather than less reports of student academic misconduct. Substantial empirical research has considered the nature of academic misconduct in higher education institutions by identifying its antecedents and correlates. But given the reproducibility crisis in social research, the quality of knowledge that students have on academic misconduct warrants further empirical corroboration. With the intent to replicate, this study used Quantitative Content Analysis to examine 2631 written responses from first-year undergraduate students as they participated in academic misconduct programming implemented by a public university in the United States. Results reported a staggering proportion of first-year students possess piecemeal (at best) or non-existent (at worst) knowledge over citations/references and cheating. Furthermore, such proportions are uneven according to specific college membership. Results corroborate prior research that first-year undergraduate students hold limited understanding of academic misconduct in its premises, patterns, and processes. In turn, results support the design and use of systematic preventive mechanisms to address academic misconduct among higher education institutions.
Enhanced cooperation increases the capacity for conflict
Authors: McDermott Rose
Published: July 2024

Enhanced cooperation increases the capacity for humans to engage in large-scale warfare. This ability provides the foundation for male coalitionary behavior, leaving open the question of whether cooperation evolved in the same way, or for the same purpose, in females. Such coalitionary behavior entrains hierarchical forms of leadership that remain inherently unstable, providing a spark for conflict to emerge.
Stability of H2O‐Rich Fluid in the Deep Mantle Indicated by the MgO‐SiO2‐H2O Phase Relations at 23 GPa and 2,000 K
Authors: Fei Hongzhan
Published: July 2024

The Earth's mantle contains significant amounts of water in the form of hydroxyl in hydrous minerals, nominally anhydrous minerals, and hydrous silicate melts. H2O fluid is thought to be present only in the shallow regions because it will always dissolve tens of weight percent of silicates by forming hydrous silicate melt in the deep mantle. Here I investigated the phase relations in the MgO‐SiO2‐H2O system by high‐pressure experiments at a pressure of 23 GPa and a temperature of 2,000 K, corresponding to the conditions at the bottom of the mantle transition zone and the topmost lower mantle. The experimental results indicate that hydrous melt can contain more than 90 wt.% of H2O, that is, it becomes H2O‐rich fluid when coexists only with stishovite. In contrast, silicate‐rich hydrous melt is formed when the system is enriched with MgO component. Therefore, H2O‐rich fluid may be stabilized in locally SiO2‐enriched rocks even at the topmost lower mantle, acting as a water source for the deep lower mantle by slab subduction. The H2O fluid also provide a possible cause for the occurrence of natural ice‐VII originated from 660 km depth.
A One Health framework for exploring zoonotic interactions demonstrated through a case study
Authors: Desvars-Larrive Amélie , Vogl Anna Elisabeth , Puspitarani Gavrila Amadea , Yang Liuhuaying , Joachim Anja , Käsbohrer Annemarie
Published: July 2024

The eco-epidemiology of zoonoses is often oversimplified to host-pathogen interactions while findings derived from global datasets are rarely directly transferable to smaller-scale contexts. Through a systematic literature search, we compiled a dataset of naturally occurring zoonotic interactions in Austria, spanning 1975–2022. We introduce the concept of zoonotic web to describe the complex relationships between zoonotic agents, their hosts, vectors, food, and environmental sources. The zoonotic web was explored through network analysis. After controlling for research effort, we demonstrate that, within the projected unipartite source-source network of zoonotic agent sharing, the most influential zoonotic sources are human, cattle, chicken, and some meat products. Analysis of the One Health 3-cliques (triangular sets of nodes representing human, animal, and environment) confirms the increased probability of zoonotic spillover at human-cattle and human-food interfaces. We characterise six communities of zoonotic agent sharing, which assembly patterns are likely driven by highly connected infectious agents in the zoonotic web, proximity to human, and anthropogenic activities. Additionally, we report a frequency of emerging zoonotic diseases in Austria of one every six years. Here, we present a flexible network-based approach that offers insights into zoonotic transmission chains, facilitating the development of locally-relevant One Health strategies against zoonoses.
Single-cell multiomics reveals ENL mutation perturbs kidney developmental trajectory by rewiring gene regulatory landscape
Authors: Song Lele , Li Qinglan , Xia Lingbo , Sahay Arushi Eesha , Qiu Qi , Li Yuanyuan , Li Haitao , Sasaki Kotaro , Susztak Katalin , Wu Hao , Wan Liling
Published: July 2024

How disruptions to normal cell differentiation link to tumorigenesis remains incompletely understood. Wilms tumor, an embryonal tumor associated with disrupted organogenesis, often harbors mutations in epigenetic regulators, but their role in kidney development remains unexplored. Here, we show at single-cell resolution that a Wilms tumor-associated mutation in the histone acetylation reader ENL disrupts kidney differentiation in mice by rewiring the gene regulatory landscape. Mutant ENL promotes nephron progenitor commitment while restricting their differentiation by dysregulating transcription factors such as Hox clusters. It also induces abnormal progenitors that lose kidney-associated chromatin identity. Furthermore, mutant ENL alters the transcriptome and chromatin accessibility of stromal progenitors, resulting in hyperactivation of Wnt signaling. The impacts of mutant ENL on both nephron and stroma lineages lead to profound kidney developmental defects and postnatal mortality in mice. Notably, a small molecule inhibiting mutant ENL’s histone acetylation binding activity largely reverses these defects. This study provides insights into how mutations in epigenetic regulators disrupt kidney development and suggests a potential therapeutic approach.
Single-cell transcriptomics analysis of bullous pemphigoid unveils immune-stromal crosstalk in type 2 inflammatory disease
Authors: Liu Tingting , Wang Zhenzhen , Xue Xiaotong , Wang Zhe , Zhang Yuan , Mi Zihao , Zhao Qing , Sun Lele , Wang Chuan , Shi Peidian , Yu Gongqi , Wang Meng , Sun Yonghu , Xue Fuzhong , Liu Hong , Zhang Furen
Published: July 2024

Bullous pemphigoid (BP) is a type 2 inflammation- and immunity-driven skin disease, yet a comprehensive understanding of the immune landscape, particularly immune-stromal crosstalk in BP, remains elusive. Herein, using single-cell RNA sequencing (scRNA-seq) and in vitro functional analyzes, we pinpoint Th2 cells, dendritic cells (DCs), and fibroblasts as crucial cell populations. The IL13-IL13RA1 ligand–receptor pair is identified as the most significant mediator of immune-stromal crosstalk in BP. Notably, fibroblasts and DCs expressing IL13RA1 respond to IL13-secreting Th2 cells, thereby amplifying Th2 cell-mediated cascade responses, which occurs through the specific upregulation of PLA2G2A in fibroblasts and CCL17 in myeloid cells, creating a positive feedback loop integral to immune-stromal crosstalk. Furthermore, PLA2G2A and CCL17 contribute to an increased titer of pathogenic anti-BP180-NC16A autoantibodies in BP patients. Our work provides a comprehensive insight into BP pathogenesis and shows a mechanism governing immune-stromal interactions, providing potential avenues for future therapeutic research.
Engineered reversible inhibition of SpyCatcher reactivity enables rapid generation of bispecific antibodies
Authors: Hentrich Christian , Putyrski Mateusz , Hanuschka Hanh , Preis Waldemar , Kellmann Sarah-Jane , Wich Melissa , Cavada Manuel , Hanselka Sarah , Lelyveld Victor S. , Ylera Francisco
Published: July 2024

The precise regulation of protein function is essential in biological systems and a key goal in chemical biology and protein engineering. Here, we describe a straightforward method to engineer functional control into the isopeptide bond-forming SpyTag/SpyCatcher protein ligation system. First, we perform a cysteine scan of the structured region of SpyCatcher. Except for two known reactive and catalytic residues, none of these mutations abolish reactivity. In a second screening step, we modify the cysteines with disulfide bond-forming small molecules. Here we identify 8 positions at which modifications strongly inhibit reactivity. This inhibition can be reversed by reducing agents. We call such a reversibly inhibitable SpyCatcher “SpyLock”. Using “BiLockCatcher”, a genetic fusion of wild-type SpyCatcher and SpyLock, and SpyTagged antibody fragments, we generate bispecific antibodies in a single, scalable format, facilitating the screening of a large number of antibody combinations. We demonstrate this approach by screening anti-PD-1/anti-PD-L1 bispecific antibodies using a cellular reporter assay.
I/O-efficient iterative matrix inversion with photonic integrated circuits
Authors: Chen Minjia , Wang Yizhi , Yao Chunhui , Wonfor Adrian , Yang Shuai , Penty Richard , Cheng Qixiang
Published: July 2024

Photonic integrated circuits have been extensively explored for optical processing with the aim of breaking the speed and energy efficiency bottlenecks of digital electronics. However, the input/output (IO) bottleneck remains one of the key barriers. Here we report a photonic iterative processor (PIP) for matrix-inversion-intensive applications. The direct reuse of inputted data in the optical domain unlocks the potential to break the IO bottleneck. We demonstrate notable IO advantages with a lossless PIP for real-valued matrix inversion and integral-differential equation solving, as well as a coherent PIP with optical loops integrated on-chip, enabling complex-valued computation and a net inversion time of 1.2 ns. Furthermore, we estimate at least an order of magnitude enhancement in IO efficiency of a PIP over photonic single-pass processors and the state-of-the-art electronic processors for reservoir training tasks and multiple-input and multiple-output (MIMO) precoding tasks, indicating the huge potential of PIP technology in practical applications.
Legionella maintains host cell ubiquitin homeostasis by effectors with unique catalytic mechanisms
Authors: Fu Jiaqi , Li Siying , Guan Hongxin , Li Chuang , Zhao Yan-Bo , Chen Tao-Tao , Xian Wei , Zhang Zhengrui , Liu Yao , Guan Qingtian , Wang Jingting , Lu Qiuhua , Kang Lina , Zheng Si-Ru , Li Jinyu , Cao Shoujing , Das Chittaranjan , Liu Xiaoyun , Song Lei , Ouyang Songying , Luo Zhao-Qing
Published: July 2024

The intracellular bacterial pathogen Legionella pneumophila modulates host cell functions by secreting multiple effectors with diverse biochemical activities. In particular, effectors of the SidE family interfere with host protein ubiquitination in a process that involves production of phosphoribosyl ubiquitin (PR-Ub). Here, we show that effector LnaB converts PR-Ub into ADP-ribosylated ubiquitin, which is further processed to ADP-ribose and functional ubiquitin by the (ADP-ribosyl)hydrolase MavL, thus maintaining ubiquitin homeostasis in infected cells. Upon being activated by actin, LnaB also undergoes self-AMPylation on tyrosine residues. The activity of LnaB requires a motif consisting of Ser, His and Glu (SHxxxE) present in a large family of toxins from diverse bacterial pathogens. Thus, our study sheds light on the mechanisms by which a pathogen maintains ubiquitin homeostasis and identifies a family of enzymes capable of protein AMPylation.
Native mass spectrometry and structural studies reveal modulation of MsbA–nucleotide interactions by lipids
Authors: Zhang Tianqi , Lyu Jixing , Yang Bowei , Yun Sangho D. , Scott Elena , Zhao Minglei , Laganowsky Arthur
Published: July 2024

The ATP-binding cassette (ABC) transporter, MsbA, plays a pivotal role in lipopolysaccharide (LPS) biogenesis by facilitating the transport of the LPS precursor lipooligosaccharide (LOS) from the cytoplasmic to the periplasmic leaflet of the inner membrane. Despite multiple studies shedding light on MsbA, the role of lipids in modulating MsbA-nucleotide interactions remains poorly understood. Here we use native mass spectrometry (MS) to investigate and resolve nucleotide and lipid binding to MsbA, demonstrating that the transporter has a higher affinity for adenosine 5’-diphosphate (ADP). Moreover, native MS shows the LPS-precursor 3-deoxy-D-manno-oct-2-ulosonic acid (Kdo)2-lipid A (KDL) can tune the selectivity of MsbA for adenosine 5’-triphosphate (ATP) over ADP. Guided by these studies, four open, inward-facing structures of MsbA are determined that vary in their openness. We also report a 2.7 Å-resolution structure of MsbA in an open, outward-facing conformation that is not only bound to KDL at the exterior site, but with the nucleotide binding domains (NBDs) adopting a distinct nucleotide-free structure. The results obtained from this study offer valuable insight and snapshots of MsbA during the transport cycle.
DBScope as a versatile computational toolbox for the visualization and analysis of sensing data from deep brain stimulation
Authors: Oliveira Andreia M. , Carvalho Eduardo , Barros Beatriz , Soares Carolina , Ferreira-Pinto Manuel J. , Vaz Rui , Aguiar Paulo
Published: July 2024

Different neurostimulators for deep brain stimulation (DBS) come already with the ability to chronically sense local field potentials during stimulation. This invaluable new data has the potential to increase our understanding of disease-related brain activity patterns, their temporal evolution, and their modulation in response to therapies. It also gives the opportunity to unveil new electrophysiological biomarkers and ultimately bring adaptive stimulation therapies closer to clinical practice. Unfortunately, there are still very limited options on how to visualize, analyze, and exploit the full potential of the sensing data from these new DBS neurostimulators. To answer this need, we developed a free open-source toolbox, named DBScope, that imports data from neurostimulation devices and can be operated in two ways: via user interface and programmatically, as a library of functions. In this way, it can be used by both clinicians during clinical sessions (for instance, to visually inspect data from the current or previous in-clinic visits), and by researchers in their research pipelines (e.g., for pre-processing, feature extraction and biomarker search). All in all, the DBScope toolbox is set to facilitate the clinical decision-making process and the identification of clinically relevant biomarkers. The toolbox is already being used in clinical and research environments, and it is freely available to download at GitHub (where it is also fully documented).
Sputtered thin film deposited laser induced graphene based novel micro-supercapacitor device for energy storage application
Authors: Sain Sourav , Chowdhury Suman , Maity Sayantan , Maity Gurupada , Roy Susanta Sinha
Published: July 2024

Pioneering flexible micro-supercapacitors, designed for exceptional energy and power density, transcend conventional storage limitations. Interdigitated electrodes (IDEs) based on laser-induced graphene (LIG), augmented with metal-oxide modifiers, harness synergies with layered graphene to achieve superior capacitance. This study presents a novel one-step process for sputtered plasma deposition of HfO2, resulting in enhanced supercapacitance performance. Introducing LIG-HfO2 micro-supercapacitor (MSC) devices with varied oxygen flow rates further boosts supercapacitance performance by introducing oxygen functional groups. FESEM investigations demonstrate uniform coating of HfO2 on LIG fibers through sputtering. Specific capacitance measurements reveal 6.4 mF/cm2 at 5 mV/s and 4.5 mF/cm2 at a current density of 0.04 mA/cm2. The LIG-HfO2 devices exhibit outstanding supercapacitor performance, boasting at least a fourfold increase over pristine LIG. Moreover, stability testing indicates a high retention rate of 97% over 5000 cycles, ensuring practical real-time applications.
Impact of bedaquiline regimen on the treatment success rates of multidrug-resistant tuberculosis patients in Egypt
Authors: Afifi Magda , Amin Wagdy , Helal Dina , Ashmawy Rasha , El-Maradny Yousra A. , Khalifa Noha , Ghazy Ramy Mohamed
Published: July 2024

Bedaquiline (BDQ), an innovative anti-tuberculous (TB) agent, has attracted attention for its potential effectiveness against drug-resistant TB. This study investigated the impact of BDQ-containing regimens on treatment success rates among multi-drug resistant tuberculosis (MDR-TB) patients in Egypt. We conducted a prospective cohort study that included all adult non-pregnant patients treated in MDR-TB centers in Egypt from April 1, 2020, to June 30, 2021, with follow-up extended until December 31, 2022. The study compared patients prescribed BDQ according to national protocols with those receiving conventional treatments for MDR-TB. Treatment success rates, mortality rates, and adverse events were analyzed using descriptive statistics, chi-square tests, logistic regression, and Kaplan–Meier survival curves. Adjustment for potential confounders was conducted using propensity score matching and Cox-hazard regressions. A total of 84 patients were included in this study. The median age of the study participants was 39 years; 22.6% were women, 57.1% were unemployed or housewives, and 1.2% had human immunodeficiency virus (HIV). Regarding the treatment regimen, 67.8% were exposed to BDQ-based treatment. Among the 55 patients (65.5%) with treatment success, a significantly higher success rate was observed in the BDQ group (73.7%) compared to the conventional group (48.1%), P = 0.042. Additionally, the incidence of skin discoloration was significantly higher in the BDQ group compared to the conventional group (38.6% versus 0.0%, P < 0.001). Despite the lower mortality incidence in the BDQ-group (14.0% versus 22.2% in the conventional group), the Kaplan–Meier survival analysis revealed no excess mortality associated with the BDQ-group, with a hazard ratio (HR) of 0.62 (95% CI 0.21–1.78, P = 0.372). Propensity score matching, while considering factors such as lesion site, diabetes mellitus, hepatitis C virus, and smoking, revealed a significant increase in the success rate associated with BDQ inclusion, with an HR of 6.79 (95% CI 1.8–25.8). In conclusion, BDQ is an effective and tolerable medication for treating MDR-TB, associated with lower mortality rates compared to conventional treatment.
Differential expression of “Candidatus Liberibacter solanacearum” genes and prophage loci in different life stages of potato psyllid
Authors: Saberi Esmaeil , Qureshi Jawwad A. , Brown Judith K.
Published: July 2024

Psyllid species, including the potato psyllid (PoP) Bactericera cockerelli (Sulc) (Triozidae) serve as host and vector of “Candidatus Liberibacter spp.” (“Ca. Liberibacter”), which also infects diverse plant hosts, including citrus and tomato. Psyllid transmission of “Ca. Liberibacter” is circulative and propagative. The time of “Ca. Liberibacter” acquisition and therefore vector life stage most competent for bacterial transmission varies by pathosystems. Here, the potato psyllid-“Ca. Liberibacter solanacearum” (CLso) pathosystem was investigated to dissect CLso-prophage interactions in the tomato plant and PoP-psyllid host by real-time quantitative reverse transcriptase amplification of CLso genes/loci with predicted involvement in host infection and psyllid-CLso transmission. Genes/loci analyzed were associated with (1) CLso-adhesion, -invasion, -pathogenicity, and -motility, (2) prophage-adhesion and pathogenicity, and (3) CLso-lysogenic cycle. Relative gene expression was quantified by qRT-PCR amplification from total RNA isolated from CLso-infected 1st–2nd and 4th–5th nymphs and teneral adults and CLso-infected tomato plants in which CLso infection is thought to occur without SC1-SC2 replication. Gene/loci expression was host-dependent and varied with the psyllid developmental stage. Loci previously associated with repressor-anti-repressor regulation in the “Ca Liberibacter asiaticus”-prophage pathosystem, which maintains the lysogenic cycle in Asian citrus psyllid Diaphorina citri, were expressed in CLso-infected psyllids but not in CLso-infected tomato plants.
Real-time deep learning-based model predictive control of a 3-DOF biped robot leg
Authors: El-Hussieny Haitham
Published: July 2024

Our research utilized deep learning to enhance the control of a 3 Degrees of Freedom biped robot leg. We created a dynamic model based on a detailed joint angles and actuator torques dataset. This model was then integrated into a Model Predictive Control (MPC) framework, allowing for precise trajectory tracking without the need for traditional analytical dynamic models. By incorporating specific constraints within the MPC, we met operational and safety standards. The experimental results demonstrate the effectiveness of deep learning models in improving robotic control, leading to precise trajectory tracking and suggesting potential for further integration of deep learning into robotic system control. This approach not only outperforms traditional control methods in accuracy and efficiency but also opens the way for new research in robotics, highlighting the potential of utilizing deep learning models in predictive control techniques.
Magnetic yolk-shell structured periodic mesoporous organosilica supported palladium as a powerful and highly recoverable nanocatalyst for the reduction of nitrobenzenes
Authors: Norouzi Meysam , Elhamifar Dawood , Kargar Shiva
Published: July 2024

A novel palladium-loaded yolk-shell structured nanomaterial with magnetite core and phenylene-based periodic mesoporous organosilica (PMO) shell (Fe3O4@YS-Ph-PMO/Pd) nanocatalyst was synthesized for the reduction of nitrobenzenes. The Fe3O4@YS-Ph-PMO/Pd was prepared through cetyltrimethylammonium bromide (CTAB) directed condensation of 1,4-bis(triethoxysilyl)benzene (BTEB) around Fe3O4@silica nanoparticles followed by treatment with palladium acetate. This nanocatalyst was characterized by using Fourier transform infrared (FT-IR) spectroscopy, thermal gravimetric analysis (TGA), low-angle and wide-angle powder X-ray diffraction (PXRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and vibrating sample magnetometer (VSM) analyses. These analyses showed a magnetic nanomaterial with high chemical and thermal stability for the designed composite. The Fe3O4@YS-Ph-PMO/Pd nanocomposite was employed as a powerful and highly recoverable catalyst in the green reduction of nitroarenes in H2O at room temperature. A variety of nitroarene derivatives were applied as substrate in the presence of 0.9 mol% of Fe3O4@YS-Ph-PMO/Pd catalyst. All nitroarenes were selectively converted to their corresponding amines with high to excellent yields (92–96%) within short reaction times (10–18 min). This catalyst was recovered and reused at least 11 times without significant decrease in efficiency and stability.
A new DES-mediated synthesis of Henna-based benzopyranophenazines and benzoxanthenetriones
Authors: Monem Arezo , Habibi Davood , Goudarzi Hadis
Published: July 2024

MTPPBr/THFTCA-DES was prepared as a new deep eutectic solvent (DES) from a mixture (molar ratio 7:3) of methyltriphenyl-phosphonium bromide (MTPPBr) and tetrahydrofuran-2,3,4,5-tetra-carboxylic acid (THFTCA), and characterized with various spectroscopic techniques, densitometer, and eutectic point. Then, it was used as a new and powerful catalyst for the synthesis of two sets of biologically important compounds, namely the Henna-based benzopyranophenazines and benzoxan-thenetriones. Solvent-free conditions, short reaction time, high efficiency, and easy recycling and separation of the DES catalyst are among the most important features of the presented method. Also, there is a nice consistency between the proposed structure of the DES compound, the integration values of the 1H NMR peaks, and the ratio of MTPPBr to THFTCA obtained from the eutectic point phase diagram. In addition, the reduction of peak splitting patterns in DES compared to the two primary materials can be good evidence of the formation of hydrogen bonds between the two components.
Deep learning application of vertebral compression fracture detection using mask R-CNN
Authors: Paik Seungyoon , Park Jiwon , Hong Jae Young , Han Sung Won
Published: July 2024

Vertebral compression fractures (VCFs) of the thoracolumbar spine are commonly caused by osteoporosis or result from traumatic events. Early diagnosis of vertebral compression fractures can prevent further damage to patients. When assessing these fractures, plain radiographs are used as the primary diagnostic modality. In this study, we developed a deep learning based fracture detection model that could be used as a tool for primary care in the orthopedic department. We constructed a VCF dataset using 487 lateral radiographs, which included 598 fractures in the L1-T11 vertebra. For detecting VCFs, Mask R-CNN model was trained and optimized, and was compared to three other popular models on instance segmentation, Cascade Mask R-CNN, YOLOACT, and YOLOv5. With Mask R-CNN we achieved highest mean average precision score of 0.58, and were able to locate each fracture pixel-wise. In addition, the model showed high overall sensitivity, specificity, and accuracy, indicating that it detected fractures accurately and without misdiagnosis. Our model can be a potential tool for detecting VCFs from a simple radiograph and assisting doctors in making appropriate decisions in initial diagnosis.
Nilotinib treatment outcomes in autosomal dominant spinocerebellar ataxia over one year
Authors: Lee Woo-Jin , Moon Jangsup , Jang Yoonhyuk , Shin Yong-Woo , Son Hyoshin , Shin Seoyi , Jeon Daejong , Han Dohyun , Lee Soon-Tae , Park Kyung-Il , Jung Keun-Hwa , Lee Sang Kun , Chu Kon
Published: July 2024

We evaluated the efficacy and safety of 1-year treatment with nilotinib (Tasigna®) in patients with autosomal dominant spinocerebellar ataxia (ADSCA) and the factors associated with responsiveness. From an institutional cohort, patients with ADSCA who completed a 1-year treatment with nilotinib (150–300 mg/day) were included. Ataxia severity was assessed using the Scale for the Rating and Assessment of Ataxia (SARA), scores at baseline and 1, 3, 6, and 12 months. A subject was categorized ‘responsive’ when the SARA score reduction at 12 M was > 0. Pretreatment serum proteomic analysis included subjects with the highest (n = 5) and lowest (n = 5) SARA score change at 12 months and five non-ataxia controls. Thirty-two subjects (18 [56.2%] females, median age 42 [30–49.5] years) were included. Although SARA score at 12 M did not significantly improve in overall population, 20 (62.5%) subjects were categorized as responsive. Serum proteomic analysis identified 4 differentially expressed proteins, leucine-rich alpha-2-glycoprotein (LRG1), vitamin-D binding protein (DBP), and C4b-binding protein (C4BP) beta and alpha chain, which are involved in the autophagy process. This preliminary data suggests that nilotinib might improve ataxia severity in some patients with ADSCA. Serum protein markers might be a clue to predict the response to nilotinib.

Trial Registration Information: Effect of Nilotinib in Cerebellar Ataxia Patients (NCT03932669, date of submission 01/05/2019).
Impact of seasonal changes in urban green spaces with diverse vegetation structures on college students' physical and mental health
Authors: Duan Yifan , Bai Hua , yang Le , Li Shuhua , Zhu Qiuchen
Published: July 2024

Based on the perceptions of college student participants in winter and summer, the effects of different vegetation structures within landscapes (single-layer woodland, tree-shrub-grass composite woodlands, tree-grass composite woodland, and single-layer grassland) and concrete squares without plants were investigated, and the skin conductivity level (SCL) and environmental perception recovery score (PRS) associated with landscape types were calculated. The results indicated that seasonal differences in landscape perception significantly affected college student participants' PRS but not their SCL scores, both in winter and summer. Viewing single-layer and tree-shrub-grass composite woodlands in summer, as well as single-layer woodland in winter, enhanced the environmental perception of the college student participants. The restorative effects of the four vegetation types in green spaces were ranked as follows: single-layer woodland, tree-shrub-grass composite woodlands, single-layer grassland, and tree-grass composite woodlands and concrete squares without plants. These findings underscore the importance of considering seasonal variations when choosing plant species for landscaping purposes, with evergreen single-layer woodland being a suitable choice for winter urban landscapes. This provides a scientific basis for assessing landscape perception and preferences in the future.
Pre-IVM with C-type natriuretic peptide promotes mitochondrial biogenesis of bovine oocytes via activation of CREB
Authors: Zhang Zehua , Jia Zhenwei
Published: July 2024

The aim of this study was to evaluate the effects of C-type natriuretic peptide (CNP) treatment prior to in vitro maturation (IVM) on mitochondria biogenesis in bovine oocyte matured in vitro and explore the related causes. The results showed that treatment with CNP before IVM significantly improved mitochondrial content, elevated the expression of genes related to mitochondria biogenesis, and increased the protein levels of phosphorylation of cAMP-response element binding protein (p-CREB) in bovine oocytes following IVM. However, further studies revealed that treatment with CNP before IVM could not increased the protein levels of p-CREB in bovine oocytes when natriuretic peptide receptor 2 activities was inhibited using the relative specific inhibitor Gö6976. In addition, treatment with CNP before IVM could not improved mitochondrial content or elevated the expression of genes related to mitochondria biogenesis in bovine oocytes when CREB activities was abolished using the specific inhibitor 666–15. In summary, these results provide evidence that treatment of bovine oocytes with CNP before IVM promotes mitochondrial biogenesis in vitro, possibly by activating CREB.