bluuebunny/crossref_metadata_2025 huggingface dataset:
STUDY OF THE STRUCTURAL FEATURES OF STRING-CONCRETE SPAN STRUCTURES
Authors:   National Transport University, Zelenskyi Bohdan
Published: August 2024

Summary. The analysis of inspection results and experience in the operation of transport facilities show that bridges with string-concrete girders according to the standard designs VTP-16 and VTP-15 are in the worst condition. The wire prestressing reinforcement of these beams, which has a small diameter of 3 mm or 5 mm, loses its cross-section over time and breaks due to corrosion. This leads to the exhaustion of the residual service life of string-concrete girders on many bridges, which has caused several collapses in Ukraine in recent years. The structural features of string-concrete girders, including the use of small-diameter prestressed wire reinforcement, play a key role in their long-term operation and reliability. The number of such structures on Ukrainian roads of national importance reaches about 500 units, and their service life is more than 60 years. Lack of proper maintenance can lead to serious economic and safety problems. Analysing the technical condition of bridge span elements and identifying defects helps to improve traffic safety, extend the service life of bridges and reduce overall costs. Effective repair and strengthening of bridge structures ensure the normal functioning of the transport infrastructure, which is critical for the economic development and security of the country. This article investigates various aspects of the operation of bridges with string-concrete girders. The causes of defects are analysed and proposals are made to temporarily preserve the stability of structures prior to major repairs or reconstruction. The structural features of bridges with string-concrete girders reveal significant shortcomings that eventually lead to serious problems. Small-diameter wire prestressing reinforcement is prone to corrosion, which reduces its cross-section and leads to rupture. This, in turn, can lead to a complete collapse of the bridge span. Keywords: bridge, span structure, string-concrete, technical condition, defects, recommendations.
ANALYSIS OF THE EXPERIENCE OF USING ASH SLAG MATERIALS OF THERMAL POWER PLANTS IN ROAD MATERIALS MADE BY COLD RECYCLING TECHNOLOGY
Authors:   National Transport University, Savenko Vyacheslav , Bykovets Mykola ,   National Transport University
Published: August 2024

Summary. This scientific text examines the analysis of domestic and world experience of using ash slag materials of thermal power plants in road materials produced by cold recycling technology. Coal is the most important primary source of energy in Ukraine. In 2019, its share accounted for 28.9% of all energy resources. There are 15 coal-fired power plants in Ukraine, the total capacity of which is 30-40% of the total installed power generation capacity in the country. As a result of the operation of thermal power plants (TPP), a significant amount of large-tonnage waste - ash and slag materials (ZShM) is generated. 360 million tons of ash slag are accumulated in TPP ash dumps. About 5-10 million tons of ash and slag are produced annually. Therefore, there is a question of reducing waste materials as materials for road construction. In Ukraine, the main method of using fly ash materials is their use in the production of cement. But at the current level of cement production, the potential of using slag in this industry has been exhausted. Therefore, the question of using ash slag materials in other industries arises. As an option, it is the use of ZSHM in road construction. Key words: road, road clothing, ash and slag materials, hydroremoval ash, takeaway ash, recycling.
Selayang Pandang Perbuatan Main Hakim Sendiri menurut Hukum Islam dan Hukum Positif
Authors: Anam Rohmatul , Fauzi Tazkia Amelia , Setyorini Tutut Dwi
Published: August 2024

Violence usually occurs because of an incident that makes an individual or group of people anxious about another individual or group who commits a crime or causes trouble in their environment. Among them is the case that happened to Edwin Hermansyah Bin Suherman in Decision Number 8/Pid.B/2019/PN.Tgl. This paper tries to answer how the views of Islamic criminal law and positive law respond to the judge's decision regarding Decision Number 8/Pid.B/2019/PN.Tgl. This research is a normative research which contains a description of the problem under study based on cases taken from court decisions and legal literature as material for analysis using a case approach and literature techniques. The results of this study indicate that; First, the decision Number 8/Pid.B/2019/PN.Tgl stated that the sentence handed down by the judge was not in accordance with the concept of qisas in Islamic Criminal Law. Second, Indonesia's Positive Law views the actions of the Main Judge as included in the category of persecution where the punishment for perpetrators of ordinary abuse is regulated in the Criminal Code. Suggestions from this study are; First, every community should have legal awareness not to take vigilante actions because the judge is the one who has the right to adjudicate a problem. Second, restitution should be included in the sentence given to the Defendant so that the criminal law is more progressive by taking into account the loss and recovery of the victim.
Lysosomal biogenesis and function in osteoclasts: a comprehensive review
Authors: Jiang Junchen , Ren Rufeng , Fang Weiyuan , Miao Jiansen , Wen Zijun , Wang Xiangyang , Xu Jiake , Jin Haiming
Published: August 2024

Lysosomes serve as catabolic centers and signaling hubs in cells, regulating a multitude of cellular processes such as intracellular environment homeostasis, macromolecule degradation, intracellular vesicle trafficking and autophagy. Alterations in lysosomal level and function are crucial for cellular adaptation to external stimuli, with lysosome dysfunction being implicated in the pathogenesis of numerous diseases. Osteoclasts (OCs), as multinucleated cells responsible for bone resorption and maintaining bone homeostasis, have a complex relationship with lysosomes that is not fully understood. Dysregulated function of OCs can disrupt bone homeostasis leading to the development of various bone disorders. The regulation of OC differentiation and bone resorption for the treatment of bone disease have received considerable attention in recent years, yet the role and regulation of lysosomes in OCs, as well as the potential therapeutic implications of intervening in lysosomal biologic behavior for the treatment of bone diseases, remain relatively understudied. This review aims to elucidate the mechanisms involved in lysosomal biogenesis and to discuss the functions of lysosomes in OCs, specifically in relation to differentiation, bone resorption, and autophagy. Finally, we explore the potential therapeutic implication of targeting lysosomes in the treatment of bone metabolic disorders.
Development of surfactant formulation for high-temperature off-shore carbonate reservoirs
Authors: Panthi Krishna , Mohanty Kishore K.
Published: August 2024

The residual oil left behind after water flooding in petroleum reservoirs can be mobilized by surfactant formulations that yield ultralow interfacial tension (IFT) with oil. However, finding ultralow IFT surfactant formulations is difficult for high-temperature, off-shore, carbonate reservoirs. These reservoirs are often water-flooded with seawater (with a lot of divalent ions), which is often incompatible with many surfactants at high temperatures. The goal of this research is to develop a surfactant formulation for an off-shore carbonate reservoir at 100°C previously flooded by seawater. Surfactant–oil–brine phase behavior was studied for formulations, starting from a single surfactant to mixtures of surfactants and a co-solvent. Mixtures of three surfactants and one co-solvent were needed to produce ultralow IFT formulations for the oil of interest. The surfactant system with polymer mobility control was tested in crushed reservoir rock packs. The cumulative oil recovery was >99% for the surfactant–polymer (SP) flood with an optimal salinity gradient. The constant salinity SP floods with seawater increased oil recovery significantly beyond the water flood (cumulative oil recovery >91%), even though the recovery was lower than that of the optimal salinity gradient SP flood. Our experimental work demonstrates the effectiveness of the surfactant formulation for a high-temperature carbonate reservoir at seawater salinity.
Gut microbiota and psoriasis: pathogenesis, targeted therapy, and future directions
Authors: Zou Xinyan , Zou Xinfu , Gao Longxia , Zhao Hanqing
Published: August 2024

Background

Psoriasis is one of the most common autoimmune skin diseases. Increasing evidence shows that alterations in the diversity and function of microbiota can participate in the pathogenesis of psoriasis through various pathways and mechanisms.

Objective

To review the connection between microbial changes and psoriasis, how microbial-targeted therapy can be used to treat psoriasis, as well as the potential of prebiotics, probiotics, synbiotics, fecal microbiota transplantation, diet, and Traditional Chinese Medicine as supplementary and adjunctive therapies.

Methods

Literature related to the relationship between psoriasis and gut microbiota was searched in PubMed and CNKI.

Results

Adjunct therapies such as dietary interventions, traditional Chinese medicine, and probiotics can enhance gut microbiota abundance and diversity in patients with psoriasis. These therapies stimulate immune mediators including IL-23, IL-17, IL-22, and modulate gamma interferon (IFN-γ) along with the NF-kB pathway, thereby suppressing the release of pro-inflammatory cytokines and ameliorating systemic inflammatory conditions.

Conclusion

This article discusses the direction of future research and clinical treatment of psoriasis from the perspective of intestinal microbiota and the mechanism of traditional Chinese medicine, so as to provide clinicians with more comprehensive diagnosis and treatment options and bring greater hope to patients with psoriasis.
Arabic or English? Multilingual users’ preferences in Dubai ATM transactions
Authors: Al-Issa Ahmad , Sulieman Hana
Published: August 2024

Language choice or preference, that is the deliberate selection of language(s) for different purposes in different contexts, situations and domains, is a complex sociolinguistic phenomenon as it is usually motivated by numerous sociolinguistic factors. This study investigates language choice between Arabic and English during automated teller machine (ATM) transactions in Dubai, a cosmopolitan city in the United Arab Emirates (UAE), and aims at exploring the factors influencing these preferences. The data were collected, using a survey questionnaire, from 566 ATM users in Dubai. The findings reveal that nearly all non-Arab participants favor English over Arabic for ATM transactions, irrespective of their length of stay in the country and their proficiency level in English and Arabic, given that Dubai ATMs offer only these two languages. On the other hand, Arab participants, including UAE nationals and Arab expatriates, tend to use Arabic more frequently than English. However, those residing in Dubai show a greater preference for English compared to those living outside Dubai. Additional factors such as age, gender, level of education, occupation, and comfort with technology were also investigated. This research illuminates the prevalent use and elevated status of English in Dubai, affirming its significance among both native and non-native Arabic speakers. Furthermore, it offers insight into the linguistic resources employed by individuals in transactional exchanges, contributing to our understanding of the complex relationship between language contact, language attitudes, language choice, and technology adoption within a multilingual urban setting. The findings underscore the importance of examining linguistic preferences within specific subdomains of multilingual communities.
A didactic experience for educating the youngest generations about seismic risk using an escape room
Authors: Gargiulo Maria Vittoria , Napolitano Ferdinando , Amoroso Ortensia , Russo Raffaella , Capuano Paolo
Published: August 2024

Effective risk communication is crucial for enhancing societal resilience. It’s not just about scientific strategies; it’s also about ensuring that communities are informed and prepared. Educating local populations, especially younger generations, is key to improving disaster readiness. Notably, engaging younger generations assumes significance, given their role as both the future of society and conduits for educating their families. Serious Games, specifically Escape Rooms, present a compelling tool for engaging and interacting with young people. These games, designed not primarily for entertainment but for educational purposes, facilitate active participant involvement, thereby enhancing learning. In our didactic approach, comprising a frontal lesson and an Escape Room, we sought to leverage the appeal of Serious Games to educate young people. This approach was particularly timely during the COVID-19 pandemic, where virtual experiences gained positive evaluations despite the inherent challenges. Italy frequently faces large magnitude earthquakes. Yet many Italians, especially young people, have low seismic risk awareness, hindering preparedness efforts. To address this issue, the use of games and interactive experiences proves promising. By involving young people, seismic risk awareness can be effectively raised, fostering a culture of safety. Throughout the implementation of the Escape Room exercise dedicated to seismic risk, we conducted an evaluation phase both before and after the activities. The insights gained from this evaluation process provided valuable feedback on the learning experience and the effectiveness of the science communication technique. Notably, the virtual nature of the escape room experience was positively evaluated, demonstrating its adaptability during the pandemic. It is imperative to acknowledge that participants in these activities were aged between 15 and 18 years old, requiring ethical considerations in the design and execution of the educational intervention. The findings are highly promising, indicating that students viewed the protocol as beneficial for understanding fundamental concepts in seismology and enhancing their perception of risk. Moreover, the protocol positively influenced students’ interest in science and geophysics. Furthermore, an aspect that remains unexplored is the extent to which the knowledge acquired by the participants was disseminated within their families, representing a potential area for future investigation.
Beyond LDL-C: unravelling the residual atherosclerotic cardiovascular disease risk landscape—focus on hypertriglyceridaemia
Authors: Bashir Bilal , Schofield Jonathan , Downie Paul , France Michael , Ashcroft Darren M. , Wright Alison K. , Romeo Stefano , Gouni-Berthold Ioanna , Maan Akhlaq , Durrington Paul N. , Soran Handrean
Published: August 2024

Aims

Historically, atherosclerotic cardiovascular disease (ASCVD) risk profile mitigation has had a predominant focus on low density lipoprotein cholesterol (LDL-C). In this narrative review we explore the residual ASCVD risk profile beyond LDL-C with a focus on hypertriglyceridaemia, recent clinical trials of therapeutics targeting hypertriglyceridaemia and novel modalities addressing other residual ASCVD risk factors.

Findings

Hypertriglyceridaemia remains a significant ASCVD risk despite low LDL-C in statin or proprotein convertase subtilisin/kexin type 9 inhibitor-treated patients. Large population-based observational studies have consistently demonstrated an association between hypertriglyceridaemia with ASCVD. This relationship is complicated by the co-existence of low high-density lipoprotein cholesterol. Despite significantly improving atherogenic dyslipidaemia, the most recent clinical trial outcome has cast doubt on the utility of pharmacologically lowering triglyceride concentrations using fibrates. On the other hand, purified eicosapentaenoic acid (EPA), but not in combination with docosahexaenoic acid (DHA), has produced favourable ASCVD outcomes. The outcome of these trials suggests alternate pathways involved in ASCVD risk modulation. Several other pharmacotherapies have been proposed to address other ASCVD risk factors targeting inflammation, thrombotic and metabolic factors.

Implications

Hypertriglyceridaemia poses a significant residual ASCVD risk in patients already on LDL-C lowering therapy. Results from pharmacologically lowering triglyceride are conflicting. The role of fibrates and combination of EPA and DHA is under question but there is now convincing evidence of ASCVD risk reduction with pure EPA in a subgroup of patients with hypertriglyceridaemia. Clinical guidelines should be updated in line with recent clinical trials evidence. Novel agents targeting non-conventional ASCVD risks need further evaluation.
Intramyocardial immunomodulation with human CD16+ monocytes to treat myocardial infarction in pig: a blind randomized preclinical trial
Authors: Ascione Raimondo , Bruno Vito D. , Johnson Tom , Sammut Eva , Bond Andrew , Lopez-Baz Daniel , Deutsch Julia , Bailey Mick , Chiribiri Amedeo , Patel Ashish , Baker Andrew , Modarai Bijan
Published: August 2024

Background

Human CD16+ monocytes (hCD16+ Ms) have proangiogenic properties. We assessed the feasibility, safety and efficacy of hCD16+ Ms in a porcine model of myocardial infarction (MI).

Methods and results

A total of 27 female Large White pigs underwent MI with reperfusion and cardiac magnetic resonance (CMR). Five days later, animals received intramyocardial injections of hCD16+ Ms in saline (n = 13) or saline only (n = 14). hCD16+ Ms were selected from leucocyte cones. Feasibility/safety endpoints included injury at injected sites, malignant arrhythmias, cancer, haematoma, left ventricular (LV) dilatation, troponin release and downstream organ injury. Co-primary efficacy outcome included LV scar and ejection fraction (LVEF) at 30-day post-injections by CMR. Immunohistochemistry included neo-angiogenesis, fibrosis, markers of myofibroblast and inflammation. Four animals were excluded before injections due to untreatable malignant arrhythmias or lung injury. Median cell number and viability were 48.75 million and 87%, respectively. No feasibility/safety concerns were associated with the use of hCD16+ Ms. The LV scar dropped by 14.5gr (from 25.45 ± 8.24 to 10.8 ± 3.4 gr; −55%) and 6.4gr (from 18.83 ± 5.06 to 12.4 ± 3.9gr; −30%) in the hCD16+ Ms and control groups, respectively (p = 0.015). The 30-day LVEF did not differ between groups, but a prespecified sub-analysis within the hCD16+ Ms group showed that LVEF was 2.8% higher and LV scar 1.9gr lower in the subgroup receiving a higher cell dose. Higher tissue levels of neo-angiogenesis, myofibroblast and IL-6 and lower levels of TGF-β were observed in the hCD16+ Ms group.

Conclusions

The use of hCD16+ Ms in acute MI is feasible, safe and associated with reduced LV scar size, increased tissue levels of neo-angiogenesis, myofibroblasts and IL-6 and reduced pro-fibrotic TGF-β at 30-day post-injections. A higher cell dose might increase the LVEF effect while reducing scar size, but this warrants validation in future studies.
Unveiling the role of long non-coding RNA MALAT1: a comprehensive review on myocardial infarction
Authors: Eshraghi Reza , Sadati Sina , Bahrami Ashkan , Mirjalili Seyed Reza , Farrokhian Alireza , Mahjoubin-Tehran Maryam , Mirzaei Hamed
Published: August 2024

Myocardial infarction (MI) stands at top global causes of death in developed countries, owing mostly to atherosclerotic plaque growth and endothelial injury-induced reduction in coronary blood flow. While early reperfusion techniques have improved outcomes, long-term treatment continues to be difficult. The function of lncRNAs extends to regulating gene expression in various conditions, both physiological and pathological, such as cardiovascular diseases. The objective of this research is to extensively evaluate the significance of the lncRNA called Metastasis associated lung adenocarcinoma transcript 1 (MALAT1) in the development and management of MI. According to research, MALAT1 is implicated in processes such as autophagy, apoptosis, cell proliferation, and inflammation in the cardiovascular system. This investigation examines recent research examining the effects of MALAT1 on heart function and its potential as a mean of diagnosis and treatment for post- MI complications and ischemic reperfusion injury.
S-Tune: SOT-MTJ manufacturing parameters tuning for securing the next generation of computing
Authors: Chowdhury Muhtasim Alam , Hossain Mousam , Mastrangelo Christopher , DeMara Ronald F. , Salehi Soheil
Published: August 2024

Hardware-based acceleration approaches for Machine Learning (ML) workloads have been embracing the significant potential of post-CMOS switching devices to attain reduced footprint and/or energy-efficient execution relative to transistor-based GPU and/or TPU-based accelerator architectures. Meanwhile, the promulgation of fabless IC chip manufacturing paradigms has heightened the hardware security concerns inherent in such approaches. Namely, unauthorized access to various supply chain stages may expose significant vulnerabilities resulting in malfunctions including subtle adversarial outcomes via the malicious generation of differentially-corrupted outputs. Whereas the Spin-Orbit Torque Magnetic Tunnel Junction (SOT-MTJ) is a leading spintronic device for use in ML accelerators, as well as holding security tokens, their manufacturing-only security exposures are identified and evaluated herein. Results indicate a novel vulnerability profile whereby an adversary without access to the circuit netlist could differentially-influence the machine learning application’s behavior. Specifically, ML recognition outputs can be significantly swayed via a global modification of oxide thickness (Tox) resulting in bit-flips of the weights in the crossbar array, thus corrupting the recognition of selected digits in MNIST dataset differentially creating an opportunity for an adversary. With just 0.05% of bits in crossbar having a flipped resistance state, digits “4” and “5” show the highest overall error rates, and digit “9” exhibit the lowest impact, with recognition accuracy of digits “2,” “3,” and “8” unaffected by changing the oxide thickness of SOT-MTJs uniformly from 0.75 nm to 1.2 nm without modifying the netlist nor even having access to the circuit design itself. Exposures and mitigation approaches to such novel and potentially damaging manufacturing-side intrusions are identified, postulated, and quantitatively assessed.
Fault diagnosis of the distribution network based on the D-S evidence theory Bayesian network
Authors: Wu Xiaogang , Zhao Hanying , Xu Wentao , Pan Wulue , Ji Qingfeng , Hua Xiujuan
Published: August 2024

Relay protection rejection and misoperation exist in the existing distribution network, which will affect the fault diagnosis results. To diagnose faults in distribution networks, this paper presents a fault diagnosis method for the distribution network based on the D-S evidence theory Bayesian network. First, the collected relay protection information is divided into two categories, protection information and circuit breaker information; the corresponding Bayesian network model is established based on their respective action logic, and the corresponding component failure probability is obtained by Bayesian backward inference. Second, the fault probabilities obtained from the two Bayesian networks are fused by the D-S evidence theory, and the obtained fault probabilities are used to diagnose the faulty component. Then, using the Bayesian network corresponding to the faulty component to perform Bayesian forward inference, the protection devices and circuit breakers are identified for misoperation or rejection to achieve the fault diagnosis of the distribution network. Finally, the correctness and reliability of the proposed diagnosis method are verified through the analysis of arithmetic cases.
Stability analysis and stabilization control of a grid-forming VSC-HVDC system
Authors: Lu Yi , Shi Gang , Chen Qian , Qiu Peng , Zhou Jianqiao , Yang Renxin , Zhang Jianwen
Published: August 2024

As the penetration of the integrated intermittent and fluctuating new energy (e.g., wind and photovoltaic power) increases, the conventional grid-following voltage source converter (VSC)-based high voltage direct current (HVDC) transmission system faces the problem of interactive instability with the grid. A novel grid-forming control strategy is proposed to overcome these issues, which adopts the dynamics of a DC capacitor to realize the function of self-synchronization with the grid. Moreover, the per-unit DC voltage can automatically track the grid frequency, acting as a phase-locked loop. Next, the small-signal model of the grid-forming VSC-HVDC system is established, and the stability of the system is analyzed using the eigenvalue analysis method and the complex power coefficient method. In addition, the stabilization controller is proposed for the grid-forming (GFM) control structure, which further enhances the grid-forming VSC-HVDC system’s stability and helps it operate stably under both stiff and weak grid conditions. Research results show that the VSC-HVDC system under the proposed grid-forming control can work stably in both stiff and weak grids. The grid-forming VSC-HVDC system is robust and can maintain stable operations with a large range variation of the parameters in the current and voltage control loop. Simulations are carried out on the PSCAD/EMTDC platform to verify the proposed grid-forming control strategy.
Construction of a prognostic model via WGCNA combined with the LASSO algorithm for stomach adenocarcinoma patients
Authors: Huang Zi-duo , Ran Wen-hua , Wang Guo-zhu
Published: August 2024

Objective

This study aimed to identify prognostic signatures to predict the prognosis of patients with stomach adenocarcinoma (STAD), which is necessary to improve poor prognosis and offer possible treatment strategies for STAD patients.

Methods

The overlapping genes between the key model genes that were screened by the weighted gene co-expression network analysis (WGCNA) and differentially expressed genes (DEGs) whose expression was different with significance between normal and tumor tissues were extracted to serve as co-expression genes. Then, enrichment analysis was performed on these genes. Furthermore, the least absolute shrinkage and selection operator (LASSO) regression was performed to screen the hub genes among overlapping genes. Finally, we constructed a model to explore the influence of polygenic risk scores on the survival probability of patients with STAD, and interaction effect and mediating analyses were also performed.

Results

DEGs included 2,899 upregulated genes and 2,896 downregulated genes. After crossing the DEGs and light-yellow module genes that were obtained by WGCNA, a total of 39 overlapping genes were extracted. The gene enrichment analysis revealed that these genes were enriched in the prion diseases, biosynthesis of unsaturated fatty acids, RNA metabolic process, hydrolase activity, etc. PIP5K1P1, PTTG3P, and SNORD15B were determined by LASSO-Cox. The prognostic prediction of the three-gene model was established. The Cox regression analysis showed that the comprehensive risk score for three genes was an independent prognosis factor.

Conclusion

PIP5K1P1, PTTG3P, and SNORD15B are related to the prognosis and overall survival of patients. The three-gene risk model constructed has independent prognosis predictive ability for STAD.
Infrared thermography and computed tomography imaging for hind limb study after immobilization-induced disuse atrophy
Authors: Martínez-Gutiérrez Berenice , García-Pelagio Karla P.
Published: August 2024

Immobilization for treatment after an injury can lead to disuse atrophy, resulting in reduced functionality and strength of the immobilized limb. In our study, we utilized infrared thermography (IR) and computed tomography (CT) ex vivo to assess both physiological and structural changes following hind limb immobilization in a young Wistar rat model. Twelve rats weighing 275 ± 30 g had their right hind limbs immobilized with a modified Thomas-splint for varying durations (3, 7, or 14 days). IR imaging using an infrared camera provided insight into limb temperature changes. For micro-CT, we implemented a stain-ethanol fixation method and a gray score which enabled us to visualize and quantify muscle alterations. Thermographic images showed an increase in temperature of up to 8% in the hind limb at supine position at 14 days due to the inflammatory process while micro-CT exhibited muscle shrinkage of 10 and 18% at 7 and 14 days, respectively. Our findings underscore the efficacy of IR and micro-CT as rapid and precise imaging modalities for detecting morphological shifts in muscle tissue, particularly in pathological conditions like atrophy.
Better clinical outcomes and lower triggering of inflammatory cytokines for allogeneic hematopoietic cell transplant recipients treated in home care versus hospital isolation – the Karolinska experience
Authors: Ringdén Olle , Svahn Britt-Marie , Moll Guido , Sadeghi Behnam
Published: August 2024

After allogeneic hematopoietic cell transplantation (Allo-HCT) and conditioning, patients are typically placed in isolated hospital rooms to prevent neutropenic infections. Since 1998, we’ve offered an alternative: home care for patients living within a one to two-hour drive of the hospital. In Sweden this approach includes daily visits by an experienced nurse and daily phone consultations with a unit physician. When necessary, patients receive transfusions, intravenous antibiotics, and total parenteral nutrition at home. Our initial study report compared 36 home care patients with 54 hospital-treated controls. Multivariate analysis found that home care patients were discharged earlier to outpatient clinics, required fewer days of total parenteral nutrition, had less acute graft-versus-host disease (GVHD) grade II-IV, and lower transplantation-related mortality (TRM) and lower costs. Long-term follow-up showed similar chronic GVHD and relapse rates in both groups, with improved survival rates in the home care group. A subsequent comparison of 146 home care patients with hospital-treated controls indicated that home care and longer home stays were associated with lower grades of acute GVHD. Home care was found to be safe and beneficial for children and adolescents. Over two decades, 252 patients received home care post-Allo-HCT without any fatalities at-home. Ten-year outcomes showed a 14% TRM and a 59% survival rate. In 2020, an independent center confirmed the reduced risk of acute GVHD grades II-IV for patients treated in home care. Here, we report for the first time that home care patients also demonstrate a less inflammatory systemic cytokine profile. We found higher levels of IFN-γ, IL-2, IL-5, IL-13, GM-CSF, and G-CSF, but lower VEGF in hospital-treated patients, which may contribute to acute GVHD grades II-IV. In conclusion, home-based treatment following Allo-HCT yields multiple promising clinical outcomes and improved systemic inflammatory markers, which may contribute to less development of life-threatening GVHD.
Tumor necrosis factor inhibitors enhance corticosteroid therapy for Stevens-Johnson syndrome and toxic epidermal necrolysis linked to immune checkpoint inhibitors: a prospective study
Authors: He Chun-Xia , Guo Lan , Qu Tao , Jin Hong-Zhong
Published: August 2024

Introduction

Immune-related epidermal necrolysis (irEN), including Stevens-Johnson Syndrome (SJS) and toxic epidermal necrolysis (TEN), represents a potentially lethal reaction to immune checkpoint inhibitors. An optimal treatment strategy remains undefined. This study evaluates the effectiveness and safety of combination therapy with corticosteroids and tumor necrosis factor inhibitors (TNFi) in treating irEN patients.

Methods

In this single-center, prospective, observational study, patients with irEN received either corticosteroid monotherapy or a combination therapy of corticosteroids and TNFi (etanercept for SJS, infliximab for TEN). The primary endpoint was re-epithelization time, with secondary endpoints including corticosteroid exposure, major adverse event incidence, acute mortality rates, and biomarkers indicating disease activity and prognosis. The study was registered at the Chinese Clinical Trial Registry (ChiCTR2100051052).

Results

Thirty-two patients were enrolled (21 SJS, 11 TEN); 14 received combination therapy and 18 received corticosteroid monotherapy. IrEN typically occurred after 1 cycle of ICI administration, with a median latency of 16 days. Despite higher SCORTEN scores in the combination group (3 vs. 2, p = 0.008), these patients experienced faster re-epithelization (14 vs. 21 days; p < 0.001), shorter corticosteroid treatment duration (22 vs. 32 days; p = 0.005), and lower prednisone cumulative dose (1177 mg vs. 1594 mg; p = 0.073). Major adverse event rates were similar between groups. Three deaths occurred due to lung infection or disseminated intravascular coagulation, with mortality rates for both groups lower than predicted. Potential risk factors for increased mortality included continuous reduction in lymphocyte subset counts (CD4+ T cells, CD8+ T cells, natural killer cells) and consistent rises in inflammatory markers (serum ferritin, interleukin-6, TNF-α). Re-epithelization time negatively correlated with body mass index and positively correlated with epidermal detachment area and serum levels of interleukin-6 and TNF-α.

Conclusions

Corticosteroids combined with TNFi markedly promote re-epithelization, reduce corticosteroid use, and decrease acute mortality in irEN patients without increasing major adverse events, offering a superior alternative to corticosteroid monotherapy. Inflammatory markers and lymphocyte subsets are valuable for assessing disease activity and prognosis.
Traversing the bench to bedside journey for iNKT cell therapies
Authors: O’Neal Julie , Mavers Melissa , Jayasinghe Reyka G. , DiPersio John F.
Published: August 2024

Invariant natural killer T (iNKT) cells are immune cells that harness properties of both the innate and adaptive immune system and exert multiple functions critical for the control of various diseases. Prevention of graft-versus-host disease (GVHD) by iNKT cells has been demonstrated in mouse models and in correlative human studies in which high iNKT cell content in the donor graft is associated with reduced GVHD in the setting of allogeneic hematopoietic stem cell transplants. This suggests that approaches to increase the number of iNKT cells in the setting of an allogeneic transplant may reduce GVHD. iNKT cells can also induce cytolysis of tumor cells, and murine experiments demonstrate that activating iNKT cells in vivo or treating mice with ex vivo expanded iNKT cells can reduce tumor burden. More recently, research has focused on testing anti-tumor efficacy of iNKT cells genetically modified to express a chimeric antigen receptor (CAR) protein (CAR-iNKT) cells to enhance iNKT cell tumor killing. Further, several of these approaches are now being tested in clinical trials, with strong safety signals demonstrated, though efficacy remains to be established following these early phase clinical trials. Here we review the progress in the field relating to role of iNKT cells in GVHD prevention and anti- cancer efficacy. Although the iNKT field is progressing at an exciting rate, there is much to learn regarding iNKT cell subset immunophenotype and functional relationships, optimal ex vivo expansion approaches, ideal treatment protocols, need for cytokine support, and rejection risk of iNKT cells in the allogeneic setting.
Enhancing the ophthalmic AI assessment with a fundus image quality classifier using local and global attention mechanisms
Authors: Wang Shengzhan , Shen Wenyue , Gao Zhiyuan , Jiang Xiaoyu , Wang Yaqi , Li Yunxiang , Ma Xiaoyu , Wang Wenhao , Xin Shuanghua , Ren Weina , Jin Kai , Ye Juan
Published: August 2024

Background

The assessment of image quality (IQA) plays a pivotal role in the realm of image-based computer-aided diagnosis techniques, with fundus imaging standing as the primary method for the screening and diagnosis of ophthalmic diseases. Conventional studies on fundus IQA tend to rely on simplistic datasets for evaluation, predominantly focusing on either local or global information, rather than a synthesis of both. Moreover, the interpretability of these studies often lacks compelling evidence. In order to address these issues, this study introduces the Local and Global Attention Aggregated Deep Neural Network (LGAANet), an innovative approach that integrates both local and global information for enhanced analysis.

Methods

The LGAANet was developed and validated using a Multi-Source Heterogeneous Fundus (MSHF) database, encompassing a diverse collection of images. This dataset includes 802 color fundus photography (CFP) images (302 from portable cameras), and 500 ultrawide-field (UWF) images from 904 patients with diabetic retinopathy (DR) and glaucoma, as well as healthy individuals. The assessment of image quality was meticulously carried out by a trio of ophthalmologists, leveraging the human visual system as a benchmark. Furthermore, the model employs attention mechanisms and saliency maps to bolster its interpretability.

Results

In testing with the CFP dataset, LGAANet demonstrated remarkable accuracy in three critical dimensions of image quality (illumination, clarity and contrast based on the characteristics of human visual system, and indicates the potential aspects to improve the image quality), recording scores of 0.947, 0.924, and 0.947, respectively. Similarly, when applied to the UWF dataset, the model achieved accuracies of 0.889, 0.913, and 0.923, respectively. These results underscore the efficacy of LGAANet in distinguishing between varying degrees of image quality with high precision.

Conclusion

To our knowledge, LGAANet represents the inaugural algorithm trained on an MSHF dataset specifically for fundus IQA, marking a significant milestone in the advancement of computer-aided diagnosis in ophthalmology. This research significantly contributes to the field, offering a novel methodology for the assessment and interpretation of fundus images in the detection and diagnosis of ocular diseases.
Peri- and intra-nodular radiomic features based on 18F-FDG PET/CT to distinguish lung adenocarcinomas from pulmonary granulomas
Authors: Tian Congna , Hu Yujing , Li Shuheng , Zhang Xinchao , Wei Qiang , Li Kang , Chen Xiaolin , Zheng Lu , Yang Xin , Qin Yanan , Bian Yanzhu
Published: August 2024

Objective

To compare the effectiveness of radiomic features based on 18F-FDG PET/CT images within (intranodular) and around (perinodular) lung nodules/masses in distinguishing between lung adenocarcinoma and pulmonary granulomas.

Methods

For this retrospective study, 18F-FDG PET/CT images were collected for 228 patients. Patients diagnosed with lung adenocarcinoma (n = 156) or granulomas (n = 72) were randomly assigned to a training (n = 159) and validation (n = 69) groups. The volume of interest (VOI) of intranodular, perinodular (1–5 voxels, termed Lesion_margin1 to Lesion_margin5) and total area (intra- plus perinodular region, termed Lesion_total1 to Lesion_total5) on PET/CT images were delineated using PETtumor and Marge tool of segmentation editor. A total of 1,037 radiomic features were extracted separately from PET and CT images, and the optimal features were selected to develop radiomic models. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC).

Results

Good and acceptable performance was, respectively, observed in the training (AUC = 0.868, p < 0.001) and validation (AUC = 0.715, p = 0.004) sets for the intranodular radiomic model. Among the perinodular models, the Lesion_margin2 model demonstrated the highest AUC in both sets (0.883 and 0.616, p < 0.001 and p = 0.122). Similarly, in terms of total models, Lesion_total2 model was found to outperform others in the training (AUC = 0.879, p < 0.001) and validation (AUC = 0.742, p = 0.001) sets, slightly surpassing the intranodular model.

Conclusion

When intra- and perinodular radiomic features extracted from the immediate vicinity of the nodule/mass up to 2 voxels distance on 18F-FDG PET/CT imaging are combined, improved differential diagnostic performance in distinguishing between lung adenocarcinomas and granulomas is achieved compared to the intra- and perinodular radiomic features alone.
Characterization and genomic analysis of Bacillus megaterium with the ability to degrade aflatoxin B1
Authors: Li Ting , Chang Xiaoxi , Qiao Zixuan , Ren Guangxi , Zhou Na , Chen Jiaxin , Jiang Dan , Liu Chunsheng
Published: August 2024

Coix seed is a good product for both medicinal and food use, which is highly susceptible to aflatoxin B1 (AFB1) contamination during field transport, storage, and processing. The aim of this study is to find microbial strains that can solve the problem of contamination of coix seed. In this study, the AFB1-degrading microorganism SX1-1 was isolated and identified as a Bacillus megaterium based on morphology, microscopy, and 16S rDNA sequencing. The optimum culture conditions for SX1-1 to degrade AFB1 were determined to be 12 h. The optimum degradation conditions were 72 h, 57°C, and an initial pH of 8.0. The highest degradation of AFB1 was observed in the fermentation supernatant of the SX1-1 strain, with a degradation rate of 97.45%. In addition, whole-genome sequencing analysis of this strain revealed the presence of a number of enzymes that could potentially degrade AFB1. Importantly, SX1-1 was able to degrade AFB1-contaminated coix seed in situ by 50.06% after co-culture. In conclusion, this strain had a high AFB1 degradation ability, and has great potential and great application as a biocontrol agent for AFB1 degradation of coix seed.
Biology, classification, and entomopathogen-based management and their mode of action on Tuta absoluta (Meyrick) in Asia
Authors: Vivekanandhan Perumal , Swathy Kannan , Sarayut Pittarate , Patcharin Krutmuang
Published: August 2024

Tuta absoluta, known as the South American tomato leaf miner, significantly impacts tomato plants (Solanum lycopersicum) economically on a global scale. This pest, belonging to the Gelechiidae family, is native to South America and was first identified in Peru in 1917. Since its discovery, T. absoluta has rapidly spread to Europe, Africa, and Asia, severely threatening tomato production in these regions. The widespread application of chemical pesticides against this pest has resulted in significant environmental harm, including contamination of soil and water, and has had negative effects on non-target species such as beneficial insects, birds, and aquatic life. Although substantial research has been conducted, biological control methods for T. absoluta remain insufficient, necessitating further study. This review covers the Biology, Classification, and Entomopathogen-Based Management of T. absoluta (Meyrick) in Asia. It provides essential insights into the pest’s life cycle, ecological impacts, and the potential of entomopathogens as biocontrol agents. The detailed information presented aims to facilitate the development of sustainable pest control strategies, minimizing environmental impact and promoting the use of entomopathogens as viable alternatives to chemical pesticides in controlling T. absoluta insect pest.
Enhancing cauliflower growth under cadmium stress: synergistic effects of Cd-tolerant Klebsiella strains and jasmonic acid foliar application
Authors: Shahid Shumila , Dar Abubakar , Hussain Azhar , Khalid Imran , Latif Muhammad , Ahmad Hafiz Tanvir , Mehmood Tariq , Aloud Saud S.
Published: August 2024

The pollution of heavy metals (HMs) is a major environmental concern for agricultural farming communities due to water scarcity, which forces farmers to use wastewater for irrigation purposes in Pakistan. Vegetables grown around the cities are irrigated with domestic and industrial wastewater from areas near mining, paint, and ceramic industries that pollute edible parts of crops with various HMs. Cadmium (Cd) is an extremely toxic metal in arable soil that enters the food chain and damages the native biota, ultimately causing a reduction in plant growth and development. However, the use of microbes and growth regulators enhances plant growth and development as well as HM immobilization into the cell wall and hinders their entry into the food chain. Thus, the integrated use of bacterial consortium along with exogenously applied jasmonic acid (JA) mitigates the adverse effect of metal stress, ultimately reducing the metal mobility into roots by soil. Therefore, the current study was conducted to check the impact of Cd-tolerant bacteria and JA on the growth, nutrient status, and uptake of Cd in the cauliflower (Brassica oleracea). Our results demonstrated that increasing concentrations of Cd negatively affect growth, physiological, and biochemical attributes, while the use of a bacterial consortium (SS7 + SS8) with JA (40 μmol L−1) significantly improved chlorophyll contents, stem fresh and dry biomass (19.7, 12.7, and 17.3%), root length and root fresh and dry weights (28.8, 15.2, and 23.0%), and curd fresh and dry weights and curd diameter (18.7, 12.6, and 15.1%). However, the maximum reduction in soil Cd, roots, and curd uptake was observed by 8, 11, and 9.3%, respectively, under integrated treatment as compared to the control. Moreover, integrating bacterial consortium and JA improves superoxide dismutase (SOD) (16.79%), peroxidase dismutase (POD) (26.96%), peroxidase (POX) (26.13%), and catalase (CAT) (26.86%). The plant nitrogen, phosphorus, and potassium contents were significantly increased in soil, roots, and curd up to 8, 11, and 9.3%, respectively. Hence, a consortium of Klebsiella strains in combination with JA is a potential phytostabilizer and it reduces the uptake of Cd from soil to roots to alleviate the adverse impact on cauliflower’s growth and productivity.