bluuebunny/crossref_metadata_2025 huggingface dataset:
Modular assurance of an Autonomous Ferry using Contract-Based Design and Simulation-based Verification Principles
Authors: Arne Glomsrud Jon , Kemna Stephanie , Vasanthan Chanjei , Zhao Luman , McGeorge Dag , Arne Pedersen Tom , Rye Torben Tobias , Rokseth Børge , Trong Nguyen Dong
Published: October 2024

With the introduction of autonomous technology into our society, e.g. autonomous shipping, it is important to assess and assure the safety of autonomous systems in a real-world context. Simulation-based testing is a common approach to attempt to verify performance of autonomous systems, but assurance also requires formal evidence. This paper introduces the Assurance of Digital Assets (ADA) framework, a structured method for the assurance of digital assets, i.e. novel, complex, or intelligent systems enabled by digital technologies, using contract-based design. Results are shown for an autonomous ferry assurance case, focusing on collision avoidance during the ferry’s transit. Further, we discuss the role of simulation-based testing in verifying compliance to contract specifications, to build the necessary evidence for an assurance case.
Gap analysis and harmonization of International Standards for Maritime Autonomous Surface Ships
Authors: Jin Seungje , Lee Kwangil
Published: October 2024

This paper addresses the challenges and solutions associated with the implementation of autonomous ships, focusing on the Maritime Autonomous Surface Ships (MASS) Code developed by the International Maritime Organization (IMO). With the goal of adopting a mandatory goal-based MASS Code by 2030, this study examines the interoperability and standardization requirements necessary for the effective global operation of autonomous ships. The paper analyses the MASS Code in relation to existing international standards, identifies gaps, and proposes standards works to accommodate the emerging technologies. Additionally, it investigate on the application of Autonomous Navigation Systems (ANS) and introduces the concepts of Shore ANS and Shore Bridge to enhance remote control capabilities. The analysis emphasizes the need for comprehensive standardization to ensure the safe and efficient operation of autonomous ships in diverse maritime environments.
Seismic Impedance Inversion Based on Improved Cycle-WGAN
Authors: Huang Wenlu , Pranto Mizanur , Yan Jianguo
Published: October 2024

The application of deep learning methods for seismic impedance inversion usually requires a large amount of labeled data to train the network, while labeled data available in practical applications is often limited, which affects the effectiveness of the relevant methods. In order to address this problem, this paper proposes one kind of deep learning method of a closed-loop cycle Wasserstein generative adversarial network (Cycle-WGAN) for seismic impedance inversion based on the combination of “data-driven and model-driven”. The method uses a small amount of labeled data and unlabeled seismic data generated by the forward modeling. It constitutes a bidirectional cycle of inversion and forward modeling through the generative and adversary networks for the inversion and generative and adversary networks for the forward modeling by convolution model, which improves the conventional GAN networks. The proposed method also introduces the Wasserstein loss function to improve the neural network’s training stability. Tested on the Marmousi model with complex structure, the proposed Cycle-WGAN network can effectively obtain the seismic impedance inversion results. Moreover, it is highly robust when seismic data are noisy and has higher accuracy than the inversion results from some conventional neural networks, such as RNN (Recurrent Neural Network), TCN (Temporal Convolutional Network, WGAN (Wasserstein Generative Adversarial Network), etc.
Evaluation of the design of an economic solar cooker applying FMEA to reduce risks and improve its reliability
Authors: Espinoza Ciro , Coronel Edgar , Custodio Maria
Published: October 2024

This research seeks to contribute to reducing greenhouse gases caused by burning wood and fossil fuels with stoves. The use of solar cookers is minimal, one of the causes being their low efficiency. The objective was to reduce the risk of low efficiency of the solar cooker in the design stage, applying the Failure Mode and Effects Analysis (FMEA) to identify the actions to be taken during the design seeking to reduce the Risk Priority Number during the optimization stage. The essential element of the solar cooker is the reflector, its improvement consisted of configuring it as a truncated cone with a parabola inscribed, whose focus coincides with the centroid of the absorber (pot), managing to reduce its risk priority number from 280 to 20.
Exploring the potential of Typha Populations for biorefineries: Opportunities in Peru
Authors: Carhuancho FM , Ramírez-Candia J
Published: October 2024

Typha species have been used for energy crops in constructed wastewater. They have a great capacity to bioremediate eutrophic waters and produce biomass. Typha represents a potential source for biobased materials, solid biomass, or cellulosic bioethanol for circular bioeconomy. The objective of this paper is to present current knowledge regarding the critical characteristics of the Typha and identify promising applications and potential for its use in Peru. Results of this work show that all plant fractions of Typha biomass (leaves and shoots, roots, and rhizomes) have a high potential for biorefinery.
Calibration of a spectrometer built at the Professional School of Physics - UNSA
Authors: Puma C F , Calla Y G , Solis J L , Postigo M , Leon-Salas W D , Avizcardo M
Published: October 2024

The present paper presents a methodology to calibrate a spectrometer. The methodology to calibrate the spectrometer was direct comparison using a calibrated spectrometer, a mercury lamp and two lasers, a red and a green one, and the solar spectrum measured by a calibrated spectrometer. As a result of the calibration, a methodology to correct the errors of the spectrometer was identified and the adjustment of the spectrometer was achieved successfully by reducing the errors in the position of the peaks to values of less than 2 nm and values of the intensity have been corrected to achieve errors of less than 11% compared with the measurements made by the calibrated spectrometer.
Rapid foresight: Information technologies in Physics lessons
Authors: Abdulayeva A B
Published: October 2024

This research, conducted as part of the curriculum in the discipline of Modern Learning Technologies, explores strategies for improving the training of future teachers in response to the dynamic educational landscape. The discipline is an integral component of the educational program designed for students aspiring to become educators. A total of 12 students participated in the study, engaging in a collaborative and iterative process to identify key areas for enhancement in teacher training. The rapid evolution of learning technologies necessitates a proactive approach in preparing future teachers for the challenges and opportunities in the educational landscape. In this study, students enrolled in the educational program for prospective teachers played an active role in the research process. The objective was to leverage the insights and perspectives of these students to identify areas for improvement in teacher training. Twelve students participating in the study were enrolled in the Modern Learning Technologies course. This cohort engaged in a rapid foresight approach, involving activities such as focus group discussions, brainstorming sessions, and collaborative workshops. The methodology aimed to gather diverse opinions on emerging trends in education and technology and to envision potential future scenarios. The findings of the study highlighted key trends in modern learning technologies, including advancements in educational technology, shifts in learning preferences, and evolving classroom dynamics. Students actively contributed to scenario-building exercises, providing valuable input into the skills and competencies they deemed essential for future teachers. The assessment of current teacher training programs revealed areas where adjustments and enhancements were deemed necessary. The active involvement of students in the research process proved to be instrumental in gaining firsthand insights into the needs and expectations of future educators. Collaborative workshops facilitated a co-creation of strategies for improving teacher training programs, ensuring that the enhancements were aligned with the dynamic nature of the educational environment. This research, conducted within the framework of the Modern Learning Technologies course, emphasizes the significance of involving students in the foresight process for enhancing teacher training. The collaborative and iterative nature of the approach ensures that the strategies developed are responsive to the evolving trends and needs in education. As the educational landscape continues to evolve, incorporating student perspectives into teacher training becomes imperative for fostering effective and adaptive educators.
Effect of bias voltage on high-temperature oxidation resistance and electrical properties of Mn–Co coating with metal interconnects for solid oxide fuel cell
Authors: Jin Yu , He Xiaodong , Liu Zijin , Yue Xiaoze , Zhang Guangan , Wang Shunhua , Shang Lunlin
Published: October 2024

This study investigated the effects of bias voltage on the microstructure, high-temperature oxidation resistance, electrical conductivity, element diffusion, and barrier of chromium poisoning cathode of Mn–Co coating on the surface of SOFCs metal interconnect SUS441 ferritic stainless steel. A series of Mn–Co coatings were prepared by magnetron sputtering technique at different bias voltages (−10, −50, −90 V) and oxidized at high temperatures for 175 h at 850 °C in an air environment. The results showed that the surface of each coating before oxidation exhibited a cauliflower-like morphology, with the crystallinity of the coating increasing with higher bias voltage. After high-temperature oxidation, especially the Mn–Co coatings prepared at −90 V bias, a dense and stable MnCo2O4 spinel structure was formed, which is crucial in inhibiting the growth of the Cr2O3 oxide layer. In addition, the coating also exhibits excellent electrical conductivity (Ea = 0.35 eV), good high-temperature oxidation resistance (1.182 mg cm−2), and a stronger ability to prevent the diffusion of Cr elements.
Convex embeddability and knot theory
Authors: Iannella Martina , Marcone Alberto , Motto Ros Luca , Weinstein Vadim
Published: October 2024

We consider countable linear orders and study the quasi-order of convex embeddability and its induced equivalence relation. We obtain both combinatorial and descriptive set-theoretic results, and further extend our research to the case of circular orders. These results are then applied to the study of arcs and knots, establishing combinatorial properties and lower bounds (in terms of Borel reducibility) for the complexity of some natural relations between these geometrical objects.
The Digital Fourth Amendment
Authors: Kerr Orin
Published: October 2024

When can the government read your email or monitor your web surfing? When can the police search your phone or copy your computer files? In the United States, the answers come from the Fourth Amendment to the Constitution and its ban on “unreasonable searches and seizures.”

The Digital Fourth Amendment: Privacy and Policing in Our Online World takes the reader inside the legal world of how courts are interpreting the Fourth Amendment in the digital age. Computers, smartphones, and the Internet have transformed criminal investigations, and even a routine crime is likely to lead to digital evidence. But courts are struggling to apply old Fourth Amendment concepts to the new digital world. Mechanically applying old rules from physical investigations doesn’t make sense, often leading to dramatic expansions of government power based only on coincidences of computer design.

Written by a prominent law professor whose scholarship has often been relied on by courts in the field, The Digital Fourth Amendment shows how judges must craft new rules for the new world of digital evidence. It explains the challenges courts confront as they translate old protections to a new technological world, bringing the reader up to date on the latest cases and rulings. Informed by legal history and the latest technology, this book gives courts a blueprint for legal change with clear rules for courts to adopt to restore our constitutional rights in the computer age.
The Physical Fourth Amendment
Authors: Kerr Orin
Published: October 2024

Today’s Fourth Amendment rules are designed to regulate the physical world. They originated in eighteenth-century disputes in England, such as Entick v. Carrington, which inspired the enactment of state constitutional protections against general warrants. In 1791, the U.S. Constitution added the Fourth Amendment, a ban on unreasonable searches and seizures. Understanding the Fourth Amendment requires understanding both the origins of the amendment and how the modern Supreme Court has interpreted its text. A “search” occurs when there is a physical invasion into private items and spaces or its modern technological equivalent, an inquiry captured by the reasonable-expectation-of-privacy test of Katz v. United States. A “seizure” occurs when the government meaningfully interferes with a possessory interest in property, such as by taking property away. A search or seizure is “unreasonable” either when no valid warrant was obtained or no exception to the warrant requirement applies. The Supreme Court’s applications of these tests attain an essential balance when applied to the traditional facts of physical investigations. Current law is mostly physical law, designed to regulate the physical facts of traditional investigations.
Buying Data
Authors: Kerr Orin
Published: October 2024

Should the Fourth Amendment limit efforts by governments to buy data? As the 2016 dispute between Apple and the Federal Bureau of Investigation showed, the free market can sometimes answer government demands for access to data. Governments may want to purchase records on the free market instead of getting warrants to compel their disclosure. And such a market today exists, offering records such as automated license plate reader (ALPR) data and app location records. Under current law, the Fourth Amendment does not apply. The Fourth Amendment allows data brokers to sell data to the government and allows governments to buy the data without constitutional oversight. The question is whether that should change: is an equilibrium-adjustment needed to preserve the Fourth Amendment’s role in an environment of data purchases? Although someday such an adjustment may be needed, the answer today is “no.” The law may want to limit government purchases of data, but buying data is not a Fourth Amendment problem.
Assessing CellaVision peripheral blood and advanced RBC application software’s impact on hematologic morphology reporting: Real-world implementation experience in a large Veterans Affairs hospital
Authors: Lundgren Cory R
Published: October 2024

Objectives

This quality improvement study, conducted at the Kansas City Veterans Affairs Medical Center in Kansas City, Missouri, examined the change in patient reporting after transitioning from manual to CellaVision software-guided differentials and slide reviews. The primary focus was blasts and schistocytes, given their clinical significance.

Methods

Three months of manual and CellaVision patient data were examined between May 2022 and February 2023. Blast and schistocyte patients were standardized to the total specimens performed and compared using 2-sample proportion testing. Other red blood cell (RBC) morphologies were also compared using this statistical analysis.

Results

Blast and schistocyte reporting after technologist review statistically increased after implementing the CellaVision software. This finding was most prevalent for low-percentage blasts. In addition, both morphologies experienced varying degrees of false-positive reporting, with 33% for low-percentage blasts and 91.7% for schistocytes. Other RBC morphologies displayed different levels of change, which could be clinically significant.

Conclusions

The CellaVision software’s increased sensitivity to blasts and schistocytes may benefit patient care, especially those with hematologic disorders. The software’s high false-positive rate can be reduced by implementing quality metrics that prioritize clinically significant cells. This can be accomplished by implementing a CellaVision Champion to monitor reporting changes, perform patient lookbacks through the software, and provide technologist education. In addition, adopting a more stringent grading scale for schistocytes could also improve the high false-positive rate. Overall, CellaVision provides the ability to enhance hematology quality metrics by providing access to how patient cells are categorized and offering prompt education.
Identifying disruptive papers in pharmacy literature that changed clinical practice: 1954-2014
Authors: Becerra Adan Z , Kam Leslie , Kim Yoona , Park Haesuk
Published: October 2024

Purpose

This study aimed to identify research publications that have significantly influenced clinical practice in pharmacy using a novel metric known as the disruption score.

Methods

We conducted a bibliometric analysis and PubMed search of pharmacy practice articles published in 11 key pharmacy journals and articles tagged with the MeSH term “pharmacy” or “pharmacist.” Utilizing a validated dataset of disruption scores encompassing articles published between 1954 and 2014, we identified the top 100 most disruptive papers alongside the top 100 most cited papers. Additionally, we explored comparisons between these lists and across various journals to gain comprehensive insights into the field’s evolution over time.

Results

A total of 59,535 articles met the inclusion criteria, of which 56,764 (95%) were published in the 11 core pharmacy practice journals we chose while 2,771 (5%) were published in other PubMed-indexed journals. Notably, the top 100 most disruptive papers were deemed more disruptive than 99.9% of the entire PubMed universe. The most cited paper was the 22nd most disruptive paper. The mean citation count among the top 100 most disruptive papers was 196. The 1990s was the most disruptive decade, and American Journal of Health-System Pharmacy was the most disruptive journal. We observed a weak correlation between disruption score and citation count.

Conclusion

 The disruption score identified an innovative body of landmark papers whose legacy will remain solidified in pharmacy practice. The disruption score offers a unique perspective on clinical significance, complementing other bibliometric indices and adding to the identification of papers that have introduced new paradigms in pharmacy.
The pragmatism of emotional-expressive words in Kazakh linguistics: A study of M. Auezov’s ‘The Way of Abai’
Authors: Telgozhayeva Kuralay , Kossymova Gulbany , Sovetova Zaure , Telgozhayeva Khadisha
Published: October 2024

The issue of the research of emotional lexemes is conditioned upon pragmatic relations, which constitute an important basis in the definition of expressive language units. The purpose of the research is to analyse features of emotional and expressive linguistic units, considering the cognitive and linguistic nature of words in M. Auezov’s work ‘The Way of Abai.’ The methods used to achieve the research objectives were: generalization, axiomatic, content analysis, and comparative analysis. The results of the work have determined that using words depends on a different range of emotions, where a particular situation influences the traditions and perceptions of the period concerned, developing a linguistic picture of the world. The practical significance of the research is in using the results of the research by linguists, experts, and specialists in the field of pedagogy and linguistics.
The Impact of Behavioral and Psychological Symptoms of Dementia on Individual’s Autonomy: a Scoping Review
Authors: Delineau Valeska Maria Eboli Bello , Ferreira Ana Rita , Passos Ligia , Fernandes Lia
Published: October 2024

The purpose of this study was to identify, map, summarize, and clarify the existing literature on the effects of behavioral and psychological symptoms of dementia (BPSD) an individual’s autonomy across all types of dementia diagnoses. The study aimed to determine whether there is a correlation between BPSD and a decrease in a person’s autonomy, as this relationship is important for improving dementia care through effective interventions. To achieve this goal, a scoping review was conducted using the Joanna Briggs Institute’s methodology for scoping reviews and the PRISMA extension for scoping reviews checklist. The inclusion criteria were: (i) population: participants with a clinical diagnosis of any type of dementia; (ii) concept: examining the relationship between one or more neuropsychiatric symptoms or BPSD and the individual’s autonomy; (iii) context: the progress of any type and any stage of dementia. The database search yielded 74 records, of which 41 fully met the pre-established eligibility criteria. Most studies in this review focused on participants with Alzheimer’s disease and analysed their functional abilities. Most studies in this review showed significant outcomes regarding the impact of BPSD on a person’s autonomy. The main BPSD investigated in the studies were depression, apathy, irritability, agitation, aggression, disinhibition, and lability. Apathy had a recurrent association with reduced autonomy in persons with dementia, while depression and psychosis were also found to have an impact on individuals’ autonomy.
ACLNDA: an asymmetric graph contrastive learning framework for predicting noncoding RNA–disease associations in heterogeneous graphs
Authors: Fu Laiyi , Yao ZhiYuan , Zhou Yangyi , Peng Qinke , Lyu Hongqiang
Published: October 2024

Noncoding RNAs (ncRNAs), including long noncoding RNAs (lncRNAs) and microRNAs (miRNAs), play crucial roles in gene expression regulation and are significant in disease associations and medical research. Accurate ncRNA–disease association prediction is essential for understanding disease mechanisms and developing treatments. Existing methods often focus on single tasks like lncRNA–disease associations (LDAs), miRNA–disease associations (MDAs), or lncRNA–miRNA interactions (LMIs), and fail to exploit heterogeneous graph characteristics. We propose ACLNDA, an asymmetric graph contrastive learning framework for analyzing heterophilic ncRNA–disease associations. It constructs inter-layer adjacency matrices from the original lncRNA, miRNA, and disease associations, and uses a Top-K intra-layer similarity edges construction approach to form a triple-layer heterogeneous graph. Unlike traditional works, to account for both node attribute features (ncRNA/disease) and node preference features (association), ACLNDA employs an asymmetric yet simple graph contrastive learning framework to maximize one-hop neighborhood context and two-hop similarity, extracting ncRNA–disease features without relying on graph augmentations or homophily assumptions, reducing computational cost while preserving data integrity. Our framework is capable of being applied to a universal range of potential LDA, MDA, and LMI association predictions. Further experimental results demonstrate superior performance to other existing state-of-the-art baseline methods, which shows its potential for providing insights into disease diagnosis and therapeutic target identification. The source code and data of ACLNDA is publicly available at https://github.com/AI4Bread/ACLNDA.
Advancing microbial diagnostics: a universal phylogeny guided computational algorithm to find unique sequences for precise microorganism detection
Authors: Sharma Gulshan Kumar , Sharma Rakesh , Joshi Kavita , Qureshi Sameer , Mathur Shubhita , Sinha Sharad , Chatterjee Samit , Nunia Vandana
Published: October 2024

Sequences derived from organisms sharing common evolutionary origins exhibit similarity, while unique sequences, absent in related organisms, act as good diagnostic marker candidates. However, the approach focused on identifying dissimilar regions among closely-related organisms poses challenges as it requires complex multiple sequence alignments, making computation and parsing difficult. To address this, we have developed a biologically inspired universal NAUniSeq algorithm to find the unique sequences for microorganism diagnosis by traveling through the phylogeny of life. Mapping through a phylogenetic tree ensures a low number of cross-contamination and false positives. We have downloaded complete taxonomy data from Taxadb database and sequence data from National Center for Biotechnology Information Reference Sequence Database (NCBI-Refseq) and, with the help of NetworkX, created a phylogenetic tree. Sequences were assigned over the graph nodes, k-mers were created for target and non-target nodes and search was performed over the graph using the depth first search algorithm. In a memory efficient alternative NoSQL approach, we created a collection of Refseq sequences in MongoDB database using tax-id and path of FASTA files. We queried the MongoDB collection for the target and non-target sequences. In both the approaches, we used an alignment free sliding window k-mer–based procedure that quickly compares k-mers of target and non-target sequences and returns unique sequences that are not present in the non-target. We have validated our algorithm with target nodes Mycobacterium tuberculosis, Neisseria gonorrhoeae, and Monkeypox and generated unique sequences. This universal algorithm is a powerful tool for generating diagnostic sequences, enabling the accurate identification of microbial strains with high phylogenetic precision.
Consensus on the prevention and repair of titanium mesh exposed wound after cranioplasty (2024 edition)
Authors: Zhang Pihong , Fu Xiaobing , Huang Yuesheng ,   Wound Repair Professional Committee of Chinese Medical Doctor Association
Published: October 2024

Titanium mesh exposure after cranioplasty is the most serious complication of this procedure. Although some clinical experience has been gradually accumulated over the years in the diagnosis and treatment of titanium mesh exposure, the treatment is often not standardized and it is difficult to achieve satisfactory repair results due to insufficient understanding of its pathogenesis and concurrent infections. To normalize the diagnosis and treatment of titanium mesh exposed wounds after cranioplasty and improve the therapeutic effect and the quality of life of patients, the Wound Repair Professional Committee of Chinese Medical Doctor Association organized an expert discussion based on the literature and current diagnosis and treatment status of titanium mesh exposed wounds after cranioplasty at home and abroad, and reached a consensus on the pathogenesis, preventive measures, and diagnosis and treatment strategies of titanium mesh exposed wounds after cranioplasty to provide reference for relevant clinicians.
Engineered extracellular vesicles for tissue repair and regeneration
Authors: Zhang Yan , Wu Dan , Zhou Chen , Bai Muran , Wan Yucheng , Zheng Qing , Fan Zhijin , Wang Xianwen , Yang Chun
Published: October 2024

Extracellular vesicles (EVs) are heterogeneous membrane-like vesicles secreted by living cells that are involved in many physiological and pathological processes and act as intermediaries of intercellular communication and molecular transfer. Recent studies have shown that EVs from specific sources regulate tissue repair and regeneration by delivering proteins, lipids, and nucleic acids to target cells as signaling molecules. Nanotechnology breakthroughs have facilitated the development and exploration of engineered EVs for tissue repair. Enhancements through gene editing, surface modification, and content modification have further improved their therapeutic efficacy. This review summarizes the potential of EVs in tissue repair and regeneration, their mechanisms of action, and their research progress in regenerative medicine. This review highlights their design logic through typical examples and explores the development prospects of EVs in tissue repair. The aim of this review is to provide new insights into the design of EVs for tissue repair and regeneration applications, thereby expanding their use in regenerative medicine.
Performance assessment of a 30.26 kW grid-connected photovoltaic plant in Egypt
Authors: Hassan Amal A , Atia Doaa M , El- Madany Hanaa T , Eliwa Aref Y
Published: October 2024

This paper presents an experimental analysis and performance evaluation of a grid-connected photovoltaic plant installed on the rooftop of the Electronics Research Institute in Cairo, Egypt. Cairo is classified as a hot-desert climate region according to the standard Koppen-Geiger climate classification system. Over a year, we monitored real-time data to assess key system performance metrics, such as energy yield, efficiencies, performance ratio, capacity factor, and losses. Based on the obtained experimental results, the highest final yield of 5.2498 hr/day was observed in the summer, whereas the lowest yield of 3.439 hr/day occurred in the winter months. The photovoltaic plant had an average annual system efficiency of 15.8%, while the photovoltaic and inverter had mean yearly efficiencies of 17.1% and 97.2%, respectively. The average annual performance ratio is 83.03%, and the capacity factor is 18.72%. The monthly total loss exhibited a linear rise alongside increasing ambient temperature and solar irradiance. The ambient temperature affected the system efficiency, photovoltaic efficiency, and performance ratio. The findings can help strengthen forecasts of future large-scale photovoltaic plants in hot desert climates. Moreover, they can guide the design, optimization, operation, and maintenance of new grid-connected photovoltaic systems.
Inward FDI and regional performance in Europe after the Great Recession
Authors: Crescenzi Riccardo , Ganau Roberto
Published: October 2024

This paper looks at inward foreign direct investment (FDI) and regional labour productivity in the aftermath of the Great Recession, exploring two FDI-induced effects. The first effect is linked with a capacity of FDI per se to trigger short-term productivity gains in response to a global shock. The second effect is associated with the degree of industrial diversification of these investment flows. The results suggest that it is not the amount of foreign investment received per se that matters for productivity recovery but its composition. A low degree of FDI diversification helped regions to gain productivity after the shock. The effect is stronger in regions with an industrial profile concentrated in a limited number of sectors, particularly in services. FDI can support regional recovery, but in the short run, it does so by matching and reinforcing existing regional specialisation profiles and to the benefit of services-oriented regions.
Exploring Dual-Targeted Therapy in the Management of Moderate to Severe Inflammatory Bowel Disease: A Retrospective Study
Authors: Bhaskar Sonya , Makovich Zachary , Mhaskar Rahul , Coughlin Emily , Seminerio-Diehl Jennifer
Published: October 2024

Background

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), often results in significant morbidity among patients with moderate to severe forms. While biologics and small molecules are effective in inducing remission, many patients experience refractory disease or extraintestinal manifestations. This study assesses the safety and efficacy of dual-targeted therapy in IBD patients treated at the Inflammatory Bowel Disease Center.

Methods

This retrospective cohort study examined 79 patients with UC or CD who received dual-targeted therapy at the University from October 2018 to August 2023. Data collected included demographics, disease characteristics, previous treatments, and clinical outcomes. Primary outcomes were endoscopic, radiographic, and patient-reported clinical improvements, with secondary outcomes focusing on safety profiles.

Results

Among the 79 patients (42 UC, 37 CD), 97 dual-targeted therapy cases were analyzed, primarily involving a biologic combined with a JAK inhibitor (90.7%). The median therapy duration was 39.1 weeks. Endoscopic improvement occurred in 69% of matched samples, with significant differences between pre- and postdual-targeted therapy Mayo scores for UC (P = .002) and Simple Endoscopic Score for CD (SES-CD) scores for CD (P = .018). The median pre- and postdual-targeted therapy Mayo scores across matched samples were 3 (range 1-3) and 1 (range 0-3), respectively, and for SES-CD scores were 12 (range 0-36) and 4 (range 0-20), respectively. Clinical improvement was reported by 73.2% of patients, with notable reductions in ESR (median 19 [range 2-124] mm/h to 9 [range 0-116] mm/h, P = .006), CRP (median 8.0 [range 0.2-78.5] mg/L to 3.0 [range 0.2-68.2] mg/L, P < .001), and albumin levels (4.0 [range 2.2-4.9] mg/dL to 4.2 [range 3.4-5.2], P < .001). Non-obesity was associated with both more endoscopic improvement (P = .002) and clinical improvement (P = .007). Adverse events occurred in 37 cases, predominantly upper respiratory tract infections and dermatologic issues, with no thromboembolic events reported.

Conclusions

Dual-targeted therapy demonstrated efficacy in improving clinical and endoscopic outcomes in patients with severe, refractory IBD and exhibited an acceptable safety profile. Despite the promising results, further research is needed to confirm these findings and determine optimal therapy combinations.
Predictors and clinical outcomes of true mitral stenosis in patients undergoing transcatheter aortic valve implantation
Authors: Yamaga Mitsuki , Izumo Masaki , Sato Yukio , Shoji Tatsuro , Miyahara Daisuke , Kobayashi Yoshikuni , Kai Takahiko , Okuno Taishi , Kuwata Shingo , Koga Masashi , Tanabe Yasuhiro , Akashi Yoshihiro J
Published: October 2024

Aims

Predictors of true degenerative mitral stenosis (MS) in patients with aortic stenosis who underwent transcatheter aortic valve implantation (TAVI) remain unknown. This study aimed to investigate the predictors and prognostic value of true degenerative MS in this population.

Methods and results

We retrospectively reviewed the records of 760 consecutive patients who underwent TAVI. The mitral valve area (MVA) was assessed using transthoracic echocardiography, and mitral valve calcification was assessed using multi-detector computed tomography. MS was defined as an MVA of ≤2.0 cm², and true MS was defined as moderate or severe MS following TAVI. In our TAVI cohort, we identified 72 (9.5%) patients with degenerative MS. Among these, true MS was observed in 38 (52.7%) patients. Echocardiographic data showed that the true MS group had a significantly lower MVA and higher trans-mitral gradient. The severity of mitral annular calcification was not significantly different between the two groups; however, the true MS group had significantly more posterior mitral leaflet and anterior mitral leaflet (AML) calcification. Multivariable logistic regression analysis showed that AML calcification was the independent predictor of true MS [adjusted odds ratio, 9.23; 95% confidence interval (CI) 2.84–29.9]. True MS was independently associated with poor prognosis (adjusted hazard ratio, 2.76; 95% CI 1.09–6.98).

Conclusion

Approximately half of the patients with concomitant degenerative MS who underwent TAVI had true MS, which was associated with a poor prognosis. Computed tomographic analysis of AML calcification was useful for predicting true MS.
Trends in Workplace Violence for Health Care Occupations and Facilities Over the Last 10 Years
Authors: Lombardi Brianna , Jensen Todd , Galloway Evan , Fraher Erin
Published: October 2024

Issues of workplace violence (WPV) in healthcare has garnered increasing attention, due to the impact on the health care worker well-being and retention. Yet, our understanding of whether and how WPV rates vary between health care facilities and occupations is limited, particularly information on growth over time. This information is needed to develop and target policies and interventions toward health care workers and settings most at risk. We examined trends in WPV among healthcare occupations and facilities over the past decade (2011-2021/2022), utilizing data from the Bureau of Labor Statistics’ Survey of Occupational Injuries and Illness (SOII). Findings reveal a 30% increase across all health care facility types between 2011 and 2021/22; however there was no difference in the average rate of WPV for health care occupations over the same time period. The increase of WPV for health care facilities began long before the pandemic, suggesting larger systemic issues are likely driving WPV. Existing state and organizational efforts aim to mitigate WPV, yet targeted interventions are crucial. Understanding variations across occupations and facilities will inform tailored strategies to safeguard healthcare workers.
The GRAS transcription factor PtrPAT1 of Poncirus trifoliata functions in cold tolerance and modulates glycine betaine content by regulating the BADH-like gene
Authors: Ming Ruhong , Fang Tian , Ling Wei , Geng Jingjing , Qu Jing , Zhang Yu , Chen Jianhua , Yao Shaochang , Li Liangbo , Huang Ding , Liu Ji-Hong
Published: October 2024

GRAS, termed after gibberellic acid insensitive (GAI), RGA (repressor of GA1), and SCR (scarecrow), is a plant-specific transcription factor crucial for plant development and stress response. However, understanding of the functions played by the GRAS members and their target genes in citrus is limited. In this study, we identified a cold stress-responsive GRAS gene from Poncirus trifoliata, designated as PtrPAT1, by yeast one-hybrid library screening using the promoter of PtrBADH-l, a betaine aldehyde dehydrogenase (BADH)-like gene. PtrPAT1, belonging to the PAT1 subfamily, was localized in the nucleus and plasma membrane, exhibited transactivation activity and showed a remarkable upregulation under cold stress. Overexpression of PtrPAT1 elevated BADH activity, increased glycine betaine (GB) accumulation, and conferred enhanced cold tolerance in transgenic tobacco plants compared with wild type, while downregulation in trifoliate orange by virus-induced gene silencing (VIGS) resulted in opposite trends. Furthermore, the activities of two antioxidant enzymes, including peroxidase (POD) and superoxide dismutase (SOD), were significantly increased in the overexpression plants, but remarkably decreased in the VIGS line, consistent with accumulation patterns of the reactive oxygen species (ROSs). PtrPAT1 was demonstrated to interact with and activate the PtrBADH-l promoter through the putative PAT1-binding motif with the core sequence of TTTCATGT, indicating that PtrBADH-l is a target gene of PtrPAT1. Taken together, these results demonstrate that PtrPAT1 positively affects cold tolerance through the regulation of GB biosynthesis by modulating PtrBADH-l expression.
The ubiquitin ligase VviPUB19 negatively regulates grape cold tolerance by affecting the stability of ICEs and CBFs
Authors: Wang Ling , Zhao Mengyu , Zhang Xue , Zhao Ting , Huang Congbo , Tang Yujin , Li Yan , Zhang Chaohong
Published: October 2024

Cold stress seriously affects plant growth and development. The ubiquitination system plays an important role by degrading and modifying substrates at the protein level. In this study, the U-box type ubiquitin ligase VviPUB19 gene was induced by low temperature (4°C) in grapevine. In Arabidopsis thaliana, the pub19 mutant, a homologous mutation of VviPUB19, exhibited enhanced cold tolerance, and the resistance phenotype of the mutant could be attenuated by VviPUB19. VviPUB19-overexpressing grape lines exhibited lower cold tolerance. Furthermore, it was revealed that VviPUB19 interacted with the cold-related transcription factors VviICE1, 2, and 3 and VviCBF1 and 2, and was involved in the degradation of them. This is the first time that an E3 ligase (VviPUB19) that interacts with CBFs and affects its protein stability has been identified. It was also shown that VviICE1, 2, and 3 positively regulated VviPUB19 promoter activity. Therefore, our results suggest that VviPUB19 reduces grape cold tolerance via participating in the CBF-dependent pathway.
High-quality genome of black wolfberry (Lycium ruthenicum Murr.) provides insights into the genetics of anthocyanin biosynthesis regulation
Authors: Xu Yuhui , Li Haoxia , Shi Tongwei , Luo Qing , Chen Yuchao , Guo Shenghu , Tian Weiwei , An Wei , Zhao Jian , Yin Yue , He Jun , Zheng Rui , Liang Xiaojie , Wang Yajun , Zhang Xiyan , Shi Zhigang , Duan Linyuan , Qin Xiaoya , Huang Ting , Zhang Bo , Wan Ru , Li Yanlong , Cao Youlong , Liu Hui , Shu Sheng , Xiong Aisheng , Zhao Jianhua
Published: October 2024

Black wolfberry (Lycium ruthenicum Murr.) is an important plant for ecological preservation. In addition, its fruits are rich in anthocyanins and have important edible and medicinal value. However, a high-quality chromosome-level genome for this species is not yet available, and the regulatory mechanisms involved in the biosynthesis of anthocyanins are unclear. In this study, haploid material was used to assemble a high-quality chromosome-level reference genome of Lycium ruthenicum, resulting in a genome size of 2272 Mb with contig N50 of 92.64 Mb, and 38 993 annotated gene models. In addition, the evolution of this genome and large-scale variations compared with the Ningxia wolfberry Lycium barbarum were determined. Importantly, homology annotation identified 86 genes involved in the regulatory pathway of anthocyanin biosynthesis, five of which [LrCHS1 (evm.TU.Chr05.295), LrCHS2 (evm.TU.Chr09.488), LrAOMT (evm.TU.Chr09.809), LrF3’5’H (evm.TU.Chr06.177), and LrAN2.1 (evm.TU.Chr05.2618)] were screened by differential expression analysis and correlation analysis using a combination of transcriptome and metabolome testing. Overexpression of these genes could significantly up- or downregulate anthocyanin-related metabolites. These results will help accelerate the functional genomic research of L. ruthenicum, and the elucidation of the genes involved in anthocyanin synthesis will be beneficial for breeding new varieties and further exploring its ecological conservation potential.
Trade-offs between receptor modification and fitness drive host-bacteriophage co-evolution leading to phage extinction or co-existence
Authors: Chen Lin , Zhao Xue , Wongso Shelyn , Lin Zhuohui , Wang Siyun
Published: October 2024

Parasite–host co-evolution results in population extinction or co-existence, yet the factors driving these distinct outcomes remain elusive. In this study, Salmonella strains were individually co-evolved with the lytic phage SF1 for 30 days, resulting in phage extinction or co-existence. We conducted a systematic investigation into the phenotypic and genetic dynamics of evolved host cells and phages to elucidate the evolutionary mechanisms. Throughout co-evolution, host cells displayed diverse phage resistance patterns: sensitivity, partial resistance, and complete resistance, to wild-type phage. Moreover, phage resistance strength showed a robust linear correlation with phage adsorption, suggesting that surface modification-mediated phage attachment predominates as the resistance mechanism in evolved bacterial populations. Additionally, bacterial isolates eliminating phages exhibited higher mutation rates and lower fitness costs in developing resistance compared to those leading to co-existence. Phage resistance genes were classified into two categories: key mutations, characterized by nonsense/frameshift mutations in rfaH-regulated rfb genes, leading to the removal of the receptor O-antigen; and secondary mutations, which involve less critical modifications, such as fimbrial synthesis and tRNA modification. The accumulation of secondary mutations resulted in partial and complete resistance, which could be overcome by evolved phages, whereas key mutations conferred undefeatable complete resistance by deleting receptors. In conclusion, higher key mutation frequencies with lower fitness costs promised strong resistance and eventual phage extinction, whereas deficiencies in fitness cost, mutation rate, and key mutation led to co-existence. Our findings reveal the distinct population dynamics and evolutionary trade-offs of phage resistance during co-evolution, thereby deepening our understanding of microbial interactions.
Metagenomic time series reveals a Western English Channel viral community dominated by members with strong seasonal signals
Authors: Bolaños Luis M , Michelsen Michelle , Temperton Ben
Published: October 2024

Marine viruses are key players of ocean biogeochemistry, profoundly influencing microbial community ecology and evolution. Despite their importance, few studies have explored continuous inter-seasonal viral metagenomic time series in marine environments. Viral dynamics are complex, influenced by multiple factors such as host population dynamics and environmental conditions. To disentangle the complexity of viral communities, we developed an unsupervised machine learning framework to classify viral contigs into “chronotypes” based on temporal abundance patterns. Analysing an inter-seasonal monthly time series of surface viral metagenomes from the Western English Channel, we identified chronotypes and compared their functional and evolutionary profiles. Results revealed a consistent annual cycle with steep compositional changes from winter to summer and steadier transitions from summer to winter. Seasonal chronotypes were enriched in potential auxiliary metabolic genes of the ferrochelatases and 2OG-Fe(II) oxygenase orthologous groups compared to non-seasonal types. Chronotypes clustered into four groups based on their correlation profiles with environmental parameters, primarily driven by temperature and nutrients. Viral contigs exhibited a rapid turnover of polymorphisms, akin to Red Queen dynamics. However, within seasonal chronotypes, some sequences exhibited annual polymorphism recurrence, suggesting that a fraction of the seasonal viral populations evolve more slowly. Classification into chronotypes revealed viral genomic signatures linked to temporal patterns, likely reflecting metabolic adaptations to environmental fluctuations and host dynamics. This novel framework enables the identification of long-term trends in viral composition, environmental influences on genomic structure, and potential viral interactions.