bluuebunny/crossref_metadata_2025 huggingface dataset:
Insights into the Role of microRNAs as Clinical Tools for Diagnosis, Prognosis, and as Therapeutic Targets in Alzheimer’s Disease
Authors: Puranik Nidhi , Song Minseok
Published: September 2024

Neurodegenerative diseases (NDDs) are a diverse group of neurological disorders characterized by alterations in the structure and function of the central nervous system. Alzheimer’s disease (AD), characterized by impaired memory and cognitive abilities, is the most prevalent type of senile dementia. Loss of synapses, intracellular aggregation of hyperphosphorylated tau protein, and extracellular amyloid-β peptide (Aβ) plaques are the hallmarks of AD. MicroRNAs (miRNAs/miRs) are single-stranded ribonucleic acid (RNA) molecules that bind to the 3′ and 5′ untranslated regions of target genes to cause post-transcriptional gene silencing. The brain expresses over 70% of all experimentally detected miRNAs, and these miRNAs are crucial for synaptic function and particular signals during memory formation. Increasing evidence suggests that miRNAs play a role in AD pathogenesis and we provide an overview of the role of miRNAs in synapse formation, Aβ synthesis, tau protein accumulation, and brain-derived neurotrophic factor-associated AD pathogenesis. We further summarize and discuss the role of miRNAs as potential therapeutic targets and biomarkers for AD detection and differentiation between early- and late-stage AD, based on recent research. In conclusion, altered expression of miRNAs in the brain and peripheral circulation demonstrates their potential as biomarkers and therapeutic targets in AD.
Biophysical Studies of Amyloid-Binding Fluorophores to Tau AD Core Fibrils Formed without Cofactors
Authors: Freitas Daniela P. , Saavedra Joana , Cardoso Isabel , Gomes Cláudio M.
Published: September 2024

Tau is an intrinsically disordered protein involved in several neurodegenerative diseases where a common hallmark is the appearance of tau aggregates in the brain. One common approach to elucidate the mechanisms behind the aggregation of tau has been to recapitulate in vitro the self-assembly process in a fast and reproducible manner. While the seeding of tau aggregation is prompted by negatively charged cofactors, the obtained fibrils are morphologically distinct from those found in vivo. The Tau AD core fragment (TADC, tau 306–378) has emerged as a new model and potential solution for the cofactor-free in vitro aggregation of tau. Here, we use TADC to further study this process combining multiple amyloid-detecting fluorophores and fibril bioimaging. We confirmed by transmission electron microscopy that this fragment forms fibrils after quiescent incubation at 37 °C. We then employed a panel of eight amyloid-binding fluorophores to query the formed species by acquiring their emission spectra. The results obtained showed that nearly all dyes detect TADC self-assembled species. However, the successful monitoring of TADC aggregation kinetics was limited to three fluorophores (X-34, Bis-ANS, and pFTAA) which yielded sigmoidal curves but different aggregation half-times, hinting to different species being detected. Altogether, this study highlights the potential of using multiple extrinsic fluorescent probes, alone or in combination, as tools to further clarify mechanisms behind the aggregation of amyloidogenic proteins.
Transcriptomic and Biochemical Analysis of the Antimicrobial Mechanism of Lipopeptide Iturin W against Staphylococcus aureus
Authors: Ji Yingyu , Sun Chaomin , Wu Shimei
Published: September 2024

Staphylococcus aureus is one of the most serious pathogens threatening food safety and public health. We have previously showed that iturin W exhibited obvious antifungal activity on plant pathogens. In the present study, we found iturin W, especially C14 iturin W, showed strong antimicrobial activity against S. aureus, and the antimicrobial mechanism of C14 iturin W was further investigated by transcriptomic analysis and a related biochemical experiment. The results showed that C14 iturin W can reduce the expression levels of genes associated with the reactive oxygen species (ROS) scavenging enzyme and genes involved in arginine biosynthesis, thus leading to the increase in ROS levels of S. aureus. Furthermore, C14 iturin W can also interfere with proton dynamics, which is crucial for cells to regulate various biological possesses. Therefore, ROS accumulation and change in proton motive force are import ways for C14 iturin W to exert the antimicrobial activity. In addition, C14 iturin W can also reduce the expression levels of genes related to virulence factors and decrease the production of enterotoxins and hemolysins in S. aureus, indicating that C14 iturin W has a good potential in food and pharmaceutical fields to reduce the harm caused by S. aureus in the future.
Molecular Characterization of the MoxR AAA+ ATPase of Synechococcus sp. Strain NKBG15041c
Authors: Mano Kota , Noi Kentaro , Oe Kumiko , Mochizuki Takahiro , Morishima Ken , Inoue Rintaro , Sugiyama Masaaki , Noguchi Keiichi , Shinohara Kyosuke , Yohda Masafumi , Yamada Akiyo
Published: September 2024

We isolated a stress-tolerance-related gene from a genome library of Synechococcus sp. NKBG15041c. The expression of the gene in E. coli confers resistance against various stresses. The gene encodes a MoxR AAA+ ATPase, which was designated SyMRP since it belongs to the MRP subfamily. The recombinant SyMRP showed weak ATPase activity and protected citrate synthase from thermal aggregation. Interestingly, the chaperone activity of SyMRP is ATP-dependent. SyMRP exists as a stable hexamer, and ATP-dependent conformation changes were not detected via analytical ultracentrifugation (AUC) or small-angle X-ray scattering (SAXS). Although the hexameric structure predicted by AlphaFold 3 was the canonical flat-ring structure, the structures observed by atomic force microscopy (AFM) and transmission electron microscopy (TEM) were not the canonical ring structure. In addition, the experimental SAXS profiles did not show a peak that should exist in the symmetric-ring structure. Therefore, SyMRP seems to form a hexameric structure different from the canonical hexameric structure of AAA+ ATPase.
Understanding Amyotrophic Lateral Sclerosis: Pathophysiology, Diagnosis, and Therapeutic Advances
Authors: Rizea Radu Eugen , Corlatescu Antonio-Daniel , Costin Horia Petre , Dumitru Adrian , Ciurea Alexandru Vlad
Published: September 2024

This review offers an in-depth examination of amyotrophic lateral sclerosis (ALS), addressing its epidemiology, pathophysiology, clinical presentation, diagnostic techniques, and current as well as emerging treatments. The purpose is to condense key findings and illustrate the complexity of ALS, which is shaped by both genetic and environmental influences. We reviewed the literature to discuss recent advancements in understanding molecular mechanisms such as protein misfolding, mitochondrial dysfunction, oxidative stress, and axonal transport defects, which are critical for identifying potential therapeutic targets. Significant progress has been made in refining diagnostic criteria and identifying biomarkers, leading to earlier and more precise diagnoses. Although current drug treatments provide some benefits, there is a clear need for more effective therapies. Emerging treatments, such as gene therapy and stem cell therapy, show potential in modifying disease progression and improving the quality of life for ALS patients. The review emphasizes the importance of continued research to address challenges such as disease variability and the limited effectiveness of existing treatments. Future research should concentrate on further exploring the molecular foundations of ALS and developing new therapeutic approaches. The implications for clinical practice include ensuring the accessibility of new treatments and that healthcare systems are equipped to support ongoing research and patient care.
Regenerating Family Member 3 Alpha Is Predictive of Mortality Following Emergent Large Vessel Occlusion
Authors: Sands Madison , McLouth Christopher J. , Frank Jacqueline A. , Maglinger Benton , Millson Nathan , Al-Kawaz Mais N. , Pahwa Shivani , Dornbos David L. , Lukins Douglas E. , Trout Amanda L. , Stowe Ann M. , Fraser Justin F. , Pennypacker Keith R.
Published: September 2024

Regenerating Family Member 3 Alpha (REG3A) is an antimicrobial protein secreted by the intestine and pancreas with additional immunomodulatory properties. Previously, we published that REG3A expression in ischemic stroke patient systemic blood, during mechanical thrombectomy (MT), is significantly associated with inflammatory cytokines and patient function on admission. This paper, however, did not investigate post-acute death rates. Therefore, we investigated plasma REG3A protein expression, during MT, in patients (n = 141) that survived or died within the end of the follow-up after MT. Subjects who died had significantly higher systemic plasma REG3A levels at the time of MT compared to survivors (p = 0.001). Age, sex, time from last known normal, and admission NIHSS were included as predictors to control for confounding variables and were all examined to determine their association in patient mortality. Logistic regression was used to demonstrate that higher odds of death were associated with increased REG3A levels (p = 0.002). REG3A demonstrated acceptable discrimination (AUC (95% CI): 0.669 (0.566–0.772) in predicting mortality. The overall model with age, sex, time from last known normal, and admission NIHSS discriminated well between survivors and those who died (AUC (95% CI): 0.784 (0.703–0.864)). In conclusion, REG3A could be promising as a biomarker to prognosticate stroke outcomes and stratify high-risk groups following acute ischemic stroke.
A Snapshot of the Most Recent Transthyretin Stabilizers
Authors: Marotta Carlo , Ciccone Lidia , Orlandini Elisabetta , Rossello Armando , Nencetti Susanna
Published: September 2024

In recent years, several strategies have been developed for the treatment of transthyretin-related amyloidosis, whose complex clinical manifestations involve cardiomyopathy and polyneuropathy. In view of this, transthyretin stabilizers represent a major cornerstone in treatment thanks to the introduction of tafamidis into therapy and the entry of acoramidis into clinical trials. However, the clinical treatment of transthyretin-related amyloidosis still presents several challenges, urging the development of new and improved therapeutics. Bearing this in mind, in this paper, the most promising among the recently published transthyretin stabilizers were reviewed. Their activity was described to provide some insights into their clinical potential, and crystallographic data were provided to explain their modes of action. Finally, structure–activity relationship studies were performed to give some guidance to future researchers aiming to synthesize new transthyretin stabilizers. Interestingly, some new details emerged with respect to the previously known general rules that guided the design of new compounds.
Identification of Tumor Suppressive miR-144-5p Targets: FAM111B Expression Accelerates the Malignant Phenotypes of Lung Adenocarcinoma
Authors: Tomioka Yuya , Seki Naohiko , Suetsugu Takayuki , Hagihara Yoko , Sanada Hiroki , Goto Yusuke , Kikkawa Naoko , Mizuno Keiko , Tanaka Kentaro , Inoue Hiromasa
Published: September 2024

Accumulating evidence suggests that the passenger strands microRNAs (miRNAs) derived from pre-miRNAs are closely involved in cancer pathogenesis. Analysis of our miRNA expression signature of lung adenocarcinoma (LUAD) and The Cancer Genome Atlas (TCGA) data revealed that miR-144-5p (the passenger strand derived from pre-miR-144) was significantly downregulated in LUAD tissues. The aim of this study was to identify therapeutic target molecules controlled by miR-144-5p in LUAD cells. Ectopic expression assays demonstrated that miR-144-5p attenuated LUAD cell aggressiveness, e.g., inhibited cell proliferation, migration and invasion abilities, and induced cell cycle arrest and apoptotic cells. A total of 18 genes were identified as putative cancer-promoting genes controlled by miR-144-5p in LUAD cells based on our in silico analysis. We focused on a family with sequence similarity 111 member B (FAM111B) and investigated its cancer-promoting functions in LUAD cells. Luciferase reporter assay showed that expression of FAM111B was directly regulated by miR-144-5p in LUAD cells. FAM111B knockdown assays showed that LUAD cells significantly suppressed malignant phenotypes, e.g., inhibited cell proliferation, migration and invasion abilities, and induced cell cycle arrest and apoptotic cells. Furthermore, we investigated the FAM111B-mediated molecular networks in LUAD cells. Identifying target genes regulated by passenger strands of miRNAs may aid in the discovery of diagnostic markers and therapeutic targets for LUAD.
Cartilage Repair: Promise of Adhesive Orthopedic Hydrogels
Authors: Karami Peyman , Laurent Alexis , Philippe Virginie , Applegate Lee Ann , Pioletti Dominique P. , Martin Robin
Published: September 2024

Cartilage repair remains a major challenge in human orthopedic medicine, necessitating the application of innovative strategies to overcome existing technical and clinical limitations. Adhesive hydrogels have emerged as promising candidates for cartilage repair promotion and tissue engineering, offering key advantages such as enhanced tissue integration and therapeutic potential. This comprehensive review navigates the landscape of adhesive hydrogels in cartilage repair, discussing identified challenges, shortcomings of current treatment options, and unique advantages of adhesive hydrogel products and scaffolds. While emphasizing the critical need for in situ lateral integration with surrounding tissues, we dissect current limitations and outline future perspectives for hydrogel scaffolds in cartilage repair. Moreover, we examine the clinical translation pathway and regulatory considerations specific to adhesive hydrogels. Overall, this review synthesizes the existing insights and knowledge gaps and highlights directions for future research regarding adhesive hydrogel-based devices in advancing cartilage tissue engineering.
Genotype Characterization and MiRNA Expression Profiling in Usher Syndrome Cell Lines
Authors: Tom Wesley A. , Chandel Dinesh S. , Jiang Chao , Krzyzanowski Gary , Fernando Nirmalee , Olou Appolinaire , Fernando M. Rohan
Published: September 2024

Usher syndrome (USH) is an inherited disorder characterized by sensorineural hearing loss (SNHL), retinitis pigmentosa (RP)-related vision loss, and vestibular dysfunction. USH presents itself as three distinct clinical types, 1, 2, and 3, with no biomarker for early detection. This study aimed to explore whether microRNA (miRNA) expression in USH cell lines is dysregulated compared to the miRNA expression pattern in a cell line derived from a healthy human subject. Lymphocytes from USH patients and healthy individuals were isolated and transformed into stable cell lines using Epstein–Barr virus (EBV). DNA from these cell lines was sequenced using a targeted panel to identify gene variants associated with USH types 1, 2, and 3. Microarray analysis was performed on RNA from both USH and control cell lines using NanoString miRNA microarray technology. Dysregulated miRNAs identified by the microarray were validated using droplet digital PCR technology. DNA sequencing revealed that two USH patients had USH type 1 with gene variants in USH1B (MYO7A) and USH1D (CDH23), while the other two patients were classified as USH type 2 (USH2A) and USH type 3 (CLRN-1), respectively. The NanoString miRNA microarray detected 92 differentially expressed miRNAs in USH cell lines compared to controls. Significantly altered miRNAs exhibited at least a twofold increase or decrease with a p value below 0.05. Among these miRNAs, 20 were specific to USH1, 14 to USH2, and 5 to USH3. Three miRNAs that are known as miRNA-183 family which are crucial for inner ear and retina development, have been significantly downregulated as compared to control cells. Subsequently, droplet digital PCR assays confirmed the dysregulation of the 12 most prominent miRNAs in USH cell lines. This study identifies several miRNA signatures in USH cell lines which may have potential utility in Usher syndrome identification.
Improving QoS Management Using Associative Memory and Event-Driven Transaction History
Authors: Di Stefano Antonella , Gollo Massimo , Morana Giovanni
Published: September 2024

Managing modern, web-based, distributed applications effectively is a complex task that requires coordinating several aspects, including understanding the relationships among their components, the way they interact, the available hardware, the quality of network connections, and the providers hosting them. A distributed application consists of multiple independent and autonomous components. Managing the application involves overseeing each individual component with a focus on global optimization rather than local optimization. Furthermore, each component may be hosted by different resource providers, each offering its own monitoring and control interfaces. This diversity adds complexity to the management process. Lastly, the implementation, load profile, and internal status of an application or any of its components can evolve over time. This evolution makes it challenging for a Quality of Service (QoS) manager to adapt to the dynamics of the application’s performance. This aspect, in particular, can significantly affect the QoS manager’s ability to manage the application, as the controlling strategies often rely on the analysis of historical behavior. In this paper, the authors propose an extension to a previously introduced QoS manager through the addition of two new modules: (i) an associative memory module and (ii) an event forecast module. Specifically, the associative memory module, functioning as a cache, is designed to accelerate inference times. The event forecast module, which relies on a Weibull Time-to-Event Recurrent Neural Network (WTTE-RNN), aims to provide a more comprehensive view of the system’s current status and, more importantly, to mitigate the limitations posed by the finite number of decision classes in the classification algorithm.
May the Source Be with You: On ChatGPT, Cybersecurity, and Secure Coding
Authors: Espinha Gasiba Tiago , Iosif Andrei-Cristian , Kessba Ibrahim , Amburi Sathwik , Lechner Ulrike , Pinto-Albuquerque Maria
Published: September 2024

Software security is an important topic that is gaining more and more attention due to the rising number of publicly known cybersecurity incidents. Previous research has shown that one way to address software security is by means of a serious game, the CyberSecurity Challenges, which are designed to raise awareness of software developers of secure coding guidelines. This game, proven to be very successful in the industry, makes use of an artificial intelligence technique (laddering technique) to implement a chatbot for human–machine interaction. Recent advances in machine learning have led to a breakthrough, with the implementation and release of large language models, now freely available to the public. Such models are trained on a large amount of data and are capable of analyzing and interpreting not only natural language but also source code in different programming languages. With the advent of ChatGPT, and previous state-of-the-art research in secure software development, a natural question arises: to what extent can ChatGPT aid software developers in writing secure software? In this work, we draw on our experience in the industry, and also on extensive previous work to analyze and reflect on how to use ChatGPT to aid secure software development. Towards this, we conduct two experiments with large language models. Our engagements with ChatGPT and our experience in the field allow us to draw conclusions on the advantages, disadvantages, and limitations of the usage of this new technology.
Assessing the Efficacy and Safety of Misoprostol Prior to Hysteroscopy in Women with Difficult Cervix: A Systematic Review and Meta-Analysis
Authors: Karimzadeh Atieh , Allahqoli Leila , Salehiniya Hamid , Hanjani Soheil , Namavari Ghazal , Fazel Anvari-Yazdi Abbas , Tahermanesh Kobra , Alkatout Ibrahim
Published: September 2024

Background/Objectives: Hysteroscopy has been used as both a diagnostic and therapeutic tool for intrauterine pathologies under direct visualization. However, this procedure may be associated with an increased risk of complications during entry, which can be reduced by cervical ripening before the operation. The efficacy of misoprostol in this context is influenced by factors such as estrogen levels, parity, and the mode of previous deliveries. This study aimed to assess the efficacy and safety of misoprostol in women with a challenging cervix while mitigating the influence of confounding variables. Methods: Three electronic databases, namely PubMed, Scopus, and ISI Web of Science, were searched until 14 May 2024. Randomized controlled trials focusing on postmenopausal patients, nulliparous women, and multiparous women with no prior history of vaginal delivery, undergoing hysteroscopy were included. The cervical width, time needed for cervical dilation, and the need for additional dilatation alongside the complications and adverse effects from all included studies were collected and analyzed using R (version 4.2.3). Results: Seven studies on premenopausal women and three on postmenopausal women were included. In premenopausal women, misoprostol significantly increased cervical width compared to placebo (SMD = 2.2, 95% CI 0.9 to 3.4) and reduced the need for additional cervical dilatation (OR = 0.36, 95% CI 0.17 to 0.74). No significant difference was found in the time required for cervical dilation between misoprostol and placebo groups. In postmenopausal women, misoprostol did not significantly affect cervical width compared to placebo (SMD = −0.55, 95% CI −1.3 to 0.21). Conclusions: Misoprostol is beneficial for cervical dilation in premenopausal women without a prior history of vaginal delivery but less effective in postmenopausal patients. While associated with postoperative risks, it reduces hysteroscopy-related complications. Future research should address discrepancies by controlling the confounding variables like menopausal status, parity, and mode of delivery to enhance the understanding of misoprostol’s effects and pinpoint the specific patient populations that would derive the greatest benefits from its use.
High-Intensity Exercise Training Impact on Cardiorespiratory Fitness, Gait Ability, and Balance in Stroke Survivors: A Systematic Review and Meta-Analysis
Authors: Baricich Alessio , Borg Margherita Beatrice , Battaglia Marco , Facciorusso Salvatore , Spina Stefania , Invernizzi Marco , Scotti Lorenza , Cosenza Lucia , Picelli Alessandro , Santamato Andrea
Published: September 2024

Stroke survivors commonly face challenges such as reduced physical activity and cardiorespiratory fitness (CRF) as well as balance and gait impairments, exacerbating their disability. While high-intensity exercise interventions have demonstrated some potential, their effects on these items remain uncertain. Therefore, our study aimed to investigate the impact of high-intensity training protocols on CRF, gait ability, and balance in stroke survivor populations. Two independent investigators systematically searched five databases for relevant RCTs following the PICO model. Through a systematic review of 25 RCTs published up to 31 May 2023, including adult first-stroke survivors, comparing high-intensity exercise training versus low-to-mild or no exercises, we evaluated outcomes such as the Six-Minute Walking Test (6 MWT), peak oxygen uptake (VO2peak), Ten-Meter Walk Test (10 MWT), Berg Balance Scale (BBS), and Timed Up and Go test (TUG). The protocol was registered in PROSPERO (registration number CRD42023456773). Meta-analyses indicated significant enhancements in CRF, as measured by 6 MWT and VO2peak, following high-intensity exercise interventions. However, no significant differences were observed in BBS, 10 MWT, and TUG. Our findings underscore the potential of high-intensity exercise interventions in ameliorating CRF among stroke survivors, although further research involving standardized protocols and long-term follow-ups is imperative to optimize rehabilitation outcomes.
Implementing Oxygen Therapy in Medical Wards—A Scoping Review to Understand Health Services Protocols and Procedures
Authors: Buchan Catherine , Khor Yet Hong , Thomas Toby , Smallwood Natasha
Published: September 2024

Background/Objectives: Conventional oxygen therapy (COT) is the cornerstone of management for hypoxaemia associated with acute respiratory failure (ARF) in wards. COT implementation guidance is provided in local health guidance documents (LHGDs). This study aimed to identify ward-delivered adult COT implementation LHGDs in Australian health services and assess their content and accuracy. Methods: A scoping review was conducted on 1 May 2022 and updated on 19 December 2023 to identify public health services COT LHGDs. Data were extracted and analysed regarding COT initiation, monitoring, maintenance and weaning, and management of clinical deterioration. Results: Thirty-seven included LHGDs, and eleven referenced the Australian COT guidelines. A definition in the LHGDs for hypoxaemia is that any oxygen saturation (SpO2) or arterial blood gas (ABG) is rare. None required ABG prior to COT initiation. Twenty-nine provided target SpO2 aims for initiation and maintenance. Fifteen did not specify the criteria for clinical review. Nine LHGDs provided guidance on weaning. Conclusions: There was considerable variation in the structure and content of COT LHGDs in Australian health services. Variations and limited guideline concordance of LHGDs may impact the quality and safety of health care. Considerations for future research include the development and implementation of standardised core LHGD recommendations for COT, as well as conducting a national oxygen audit to better measure and benchmark the safety and quality of care.
Management of Otogenic Meningitis: A Proposal for Practical Guidelines from a Multicenter Experience with a Systematic Review
Authors: Rubini Alessia , Ronzani Guglielmo , D’Alessandro Edoardo , Marchioni Daniele
Published: September 2024

Background: Otogenic meningitis represents the most common and life-threatening complication of infective middle ear diseases. However, no guidelines are available to describe the optimal management strategy and the role of surgical intervention. Methods: A six-year multicenter retrospective study on consecutive patients treated for otogenic meningitis caused by acute otitis and re-exacerbation of chronic otitis at the University Hospital of Verona and Modena was performed, and a systematic review regarding acute otitis media-related meningitis in accordance with the PRISMA 2020 statement was then conducted. Results: From the clinical chart analysis, 16 patients with surgical indications according to our decision-making flow chart were reviewed, with most of them undergoing surgery within 7 days of admission (n = 13, 81%). The systematic review ultimately utilized 24 studies (16 case reports and 8 case series) published between 1990 and 2023, with the overall analysis involving a total of 181 patients. Conclusion: The primary treatment for acute bacterial meningitis relies on antibiotic therapy, with surgical intervention being employed in the event of complications and when the initial treatment is not effective within 48 h. The objective of surgery is to sterilize the tympanic and mastoid cavity, thereby eradicating the suspected infective foci and managing any eventual intracranial complications.
Pushing the Survival Bar Higher: Two Decades of Innovation in Lung Transplantation
Authors: Aburahma Khalil , de Manna Nunzio Davide , Kuehn Christian , Salman Jawad , Greer Mark , Ius Fabio
Published: September 2024

Survival after lung transplantation has significantly improved during the last two decades. The refinement of the already existing extracorporeal life support (ECLS) systems, such as extracorporeal membrane oxygenation (ECMO), and the introduction of new techniques for donor lung optimization, such as ex vivo lung perfusion (EVLP), have allowed the extension of transplant indication to patients with end-stage lung failure after acute respiratory distress syndrome (ARDS) and the expansion of the donor organ pool, due to the better evaluation and optimization of extended-criteria donor (ECD) lungs and of donors after circulatory death (DCD). The close monitoring of anti-HLA donor-specific antibodies (DSAs) has allowed the early recognition of pulmonary antibody-mediated rejection (AMR), which requires a completely different treatment and has a worse prognosis than acute cellular rejection (ACR). As such, the standardization of patient selection and post-transplant management has significantly contributed to this positive trend, especially at high-volume centers. This review focuses on lung transplantation after ARDS, on the role of EVLP in lung donor expansion, on ECMO as a principal cardiopulmonary support system in lung transplantation, and on the diagnosis and therapy of pulmonary AMR.
Prognostication in Epilepsy with Integrated Analysis of Blood Parameters and Clinical Data
Authors: Park Kyung-Il , Hwang Sungeun , Son Hyoshin , Moon Jangsup , Lee Soon-Tae , Jung Keun-Hwa , Jung Ki-Young , Chu Kon , Lee Sang Kun
Published: September 2024

Background/Objectives: Determining the outcome of epilepsy is crucial for making proactive and timely treatment decisions and for counseling patients. Recent research efforts have focused on using various imaging techniques and EEG for prognostication; however, there is insufficient evidence regarding the role of blood parameters. Our study aimed to investigate the additional prognostic value of routine blood parameters in predicting epilepsy outcomes. Methods: We analyzed data from 1782 patients who underwent routine blood tests within 90 days of their first visit and had a minimum follow-up duration of three years. The etiological types were structural (35.1%), genetic (14.2%), immune (4.7%), infectious (2.9%), and unknown (42.6%). The outcome was defined as the presence of seizures in the last year. Results: Initially, a multivariate analysis was conducted based on clinical variables, MRI data, and EEG data. This analysis revealed that sex, age of onset, referred cases, epileptiform discharge, structural etiology, and the number of antiseizure medications were related to the outcome, with an area under the curve (AUC) of 0.705. Among the blood parameters, fibrinogen, bilirubin, uric acid, and aPTT were significant, with AUCs of 0.602, 0.597, 0.455, and 0.549, respectively. Including these blood parameters in the analysis slightly improved the AUC to 0.710. Conclusions: Some blood parameters were found to be related to the final outcome, potentially paving the way to understanding the mechanisms of epileptogenesis and drug resistance.
Endoscopic Retrograde Cholangio-Pancreatography and Endoscopic Ultrasound in the Management of Paediatric Acute Recurrent Pancreatitis and Chronic Pancreatitis
Authors: Joshi Deepak , Shafi Taimur , Al-Farsi Usama , Keane Margaret G. , Grammatikopoulos Tassos , Kronfli Rania , Makin Erica , Davenport Mark , Hayward Elizabeth , Pool Andrew , Reffitt David , Devlin John , Harrison Philip
Published: September 2024

Objectives: To evaluate the role of ERCP (endoscopic retrograde cholangio-pancreatography) and EUS (endoscopic ultrasound) and to describe the efficacy and safety of these procedures in a paediatric cohort with chronic pancreatitis (CP) and acute recurrent pancreatitis (ARP). Methods: All patients (<18 years) undergoing an ERCP or EUS for ARP and CP between January 2008 and December 2022 were included. Data collection included indications for the procedure, technical success, adverse events and outcome data. Results: A total of 222 ERCPs were performed in 98 patients with CP and ARP (60% female, median age 10 years). The commonest indications were a main pancreatic duct stricture (PD) with or without a stone within the main PD. Successful cannulation was achieved in 98% of cases. Improved stricture resolution was demonstrated in 63% of patients. The overall adverse event rate for ERCP was low (n = 8/222, 3.6%). An improvement in abdominal pain was demonstrated in (75/98) 76% of patients. Their Body Mass Index also significantly improved post ERCP (15.5 ± 1.41 vs. 12.9 ± 1.16 kg/m2, p = 0.001). A total of 54 EUS procedures were undertaken in 48 individuals. Moreover, 35 individuals underwent a therapeutic EUS procedure, for which the commonest indication was the drainage of a pancreatic fluid collection. The overall complication rate was low (n = 2.4%) in all EUS cases. Conclusions: ERCP and EUS can be safely and effectively used in a paediatric population with indications analogous to an adult cohort.
Application of the Self-Assembling Peptide Hydrogel RADA16 for Hemostasis during Tonsillectomy: A Feasibility Study
Authors: Michaels Joshua , Kaleva Anna I. , Bateman Laura , Wakelam Oliver , Stephens Joanna
Published: September 2024

Tonsillectomy is a common surgical procedure but carries a high risk of readmission for secondary bleeding and pain. This study evaluated the feasibility and effectiveness of using the hemostatic self-assembling peptide hydrogel RADA16 (PuraBond, 3-D Matrix SAS; Caluire et Cuire, France) to control bleeding from the tonsillectomy wound bed. Readmission/re-operation rates were compared between a prospective case series of 21 primarily adult tonsillectomy patients treated with topical RADA16 and an untreated historical Control group of 164 patients who underwent tonsillectomy by 10 surgeons at a single tertiary hospital in the UK between March 2019 and June 2022. Cumulative readmission rates for any reason were 2-fold elevated in Control subjects (18.9%; n = 31/164 subjects) compared to patients treated intra-operatively with RADA16 hemostatic hydrogel (9.5%; n = 2/21) (p = 0.378). Readmission rates for postoperative bleeding were 3-fold higher in Controls (14.6%; n = 24/164 subjects) than in the RADA16-treated group (4.8%; n = 1/21) (p = 0.317). A similar rate of retreatment for pain was recorded in the Control (4.3%; n = 7/164) and RADA16 (4.8%; n = 1/21) groups (p = 0.999). Two Control subjects (1.2%) required re-operation for recalcitrant bleeding; no RADA16 subject (0.0%) required re-operation for any reason. No device-related adverse events occurred in the RADA16 group. Surgeons were pleased with the easy learning curve and technical feasibility associated with intra-operatively administering RADA16 hemostatic hydrogel. Intra-operative hemostasis using RADA16 peptide hydrogel was straightforward and was associated with a trend of 3-fold lower rates of readmission for postoperative bleeding events than untreated Control subjects.
Factors Impacting Intent to Share Multigenic Cancer Testing Results in a Community Hospital Setting
Authors: Siddiqui Wamia , Pacyna Joel E. , Phelan Sean M. , Jones Jeremy C. , Samadder N. Jewel , Sharp Richard R.
Published: September 2024

Background/Objectives: Multi-gene, multi-cancer, hereditary cancer risk screenings may be useful in cancer prevention and treatment, not only for cancer patients but also for patients’ family members. If genetic cancer screening is to have the widest possible benefit, it must be extended into diverse cancer care settings that serve diverse patient communities, providing cancer patients and their relatives with individualized cancer risk evaluations. Little research, to date, has examined the impact of extending multigenic cancer screening into diverse settings. Without empirical data characterizing the support needs of cancer patients and their family members, we may not adequately satisfy the needs of all patients and risk exacerbating existing disparities in cancer care and outcomes. Methods: We examined patient perspectives on the sharing of genetic results with at-risk family members by surveying a racially diverse sample of cancer patients receiving a multi-gene, multi-cancer risk screen in a community hospital setting. Results: In a survey of 230 cancer patients, we found that intent to share results with family members was high but varied across family member types. More respondents planned to disclose results to at least one sister (82.5%) compared to at least one brother (73.1%). Over one-fourth of participants (27.4%) were either uncertain about sharing or intended to withhold their genomic screening results from at least one at-risk family member eligible for cascade testing. Participants were more likely to withhold their results from a sibling than from a child. Furthermore, intent to share across all family member types was lower if probands failed to identify at least one benefit to sharing. Conclusions: Understanding factors associated with decisions to share results with at-risk relatives in diverse patient populations can help clinicians support cascade genetic cancer screenings in diverse communities and settings.
Analysis of the Spatiotemporal Differentiation and Influencing Factors of Land Use Efficiency in the Beijing–Tianjin–Hebei Urban Agglomeration
Authors: Huang Haixin , Yang Jiageng
Published: September 2024

Optimizing urban land use is of significant practical importance for promoting economic development, enhancing the standard of living for individuals residing in metropolitan areas, enhancing urban infrastructure and public services, driving urban transformation and upgrading, and attaining synchronized progress of the economy, society, and environment. This paper uses the super-efficiency SBM model to measure the urban land use efficiency (ULUE) of 13 cities in the Beijing–Tianjin–Hebei (BTH) urban agglomeration from 2005 to 2020 and explores the spatiotemporal evolution characteristics and influencing factors of ULUE in this urban agglomeration using analysis of spatial data and application of geographic detector methods. The results show that (1) from 2005 to 2020, the ULUE of the BTH urban agglomeration had an initial rise followed by a decline; however, the overall efficiency score is above 1, suggesting an overall effective state; (2) a distribution pattern with Beijing as its core was established, exhibiting greater ULUE in the northern region and poorer efficiency in the southern region, with significant correlation characteristics in efficiency values between adjacent cities; and (3) capital input, labor input, social welfare, and ecological environment are all influencing factors that promote the improvement in ULUE in the BTH region, and the interaction of any two factors explains the ULUE in this region better than a single factor. The empirical research results can provide useful references for improving the input–output ratio of land units and further spatial planning and policy formulation in the BTH region.
Social Farming in EU from Legal to Sociological Perspective: Developing European Solution
Authors: Miribung Georg
Published: September 2024

Social farming is a much-studied concept in the European Union, but debates continue on the issues of standardised content and terminology. Therefore, this study involved an empirical analysis of various social farming concepts, outlining a way in which relevant rules can be designed at the European level. Various models of social farming were empirically analysed, with a focus on the (a) aim of the organisation, (b) actors within and outside the organisation, and (c) communication and decision-making structures. This study demonstrates that a European-level legal act should be adopted to achieve standardisation; however, full harmonisation is not desirable, at least not at present. It will be necessary to oblige Member States to catalogue specific activities to be covered by the term social farming in a given legal system. The pivotal point here is the multifunctional idea of agriculture, which ultimately means that social agriculture will have to support traditional agricultural activities, an approach that could be used to promote social farming systematically. The main feature of this proposal is the implementation of an open, subsidiary approach to do justice to the versatility of social farming.
Emergency-Driven Multiple Simultaneous Invasive Procedures in Haemophilia
Authors: Ursu Cristina Emilia , Șerban Margit , Pătrașcu Jenel Marian , Coriu Daniel , Pătrașcu Jenel Marian , Ioniță Ioana , Trăilă Adina , Tomuleasa Ciprian , Săvescu Delia , Brânză Melen , Ivan Codruţ , Arghirescu Teodora Smaranda
Published: September 2024

Despite the controversies regarding the appropriateness and justification of simultaneous bi- and multi-concomitant surgical procedures, this operative technique is increasingly undertaken for economic reasons. This paper discusses three cases of simultaneous interventions: two involving osteoarticular procedures and one involving a complex approach encompassing general and plastic surgery. The indications in emergency-driven cases are mandatory, life-saving, and limb-saving, and not subject to debate.
Glucose-Free Solutions Mediated Inhibition of Oxidative Stress and Oxidative Stress-Related Damages in Peritoneal Dialysis: A Promising Solution
Authors: Basso Anna , Cacciapuoti Martina , Stefanelli Lucia Federica , Nalesso Federico , Calò Lorenzo A.
Published: September 2024

Oxidative stress (OxSt) and inflammation are common in end-stage renal disease and dialysis patients; they are known risk factors for cardiovascular disease and mortality. In peritoneal dialysis (PD), OxSt and inflammation are even further increased compared to the already increased oxidative stress of their pre-dialysis phase. This is due to the high glucose-based solutions currently used, whose continuous contact with the peritoneal membrane can induce significant long-term morphological and functional changes (mesothelial to mesenchymal transition, thickening, neo-angiogenesis and fibrosis) of the peritoneal membrane. Oxidative stress plays a very important role in these processes, which may compromise the peritoneal dialysis procedure. There is, therefore, the need for more biocompatible dialysis fluids with polymers other than glucose to prevent and treat OxSt and inflammation. The most known and used of such glucose-free and more biocompatible peritoneal dialysis solutions is icodextrin, which has shown a protective effect from oxidative stress. This has supported the consideration of the use of glucose-free-based peritoneal dialysis fluids in order to reduce oxidative stress and improve peritoneal membrane survival. Studies investigating peritoneal dialysis with the use of osmo-metabolic agents (L-carnitine, xylitol and their combination) in peritoneal fluids replacing glucose-based fluids are, in fact, ongoing. They represent a promising strategy to reduce OxSt, preserve the peritoneal membrane’s integrity and improve patients’ outcome.
Physico-Mechanical Characteristics of Gypsum–Fiber Boards Manufactured with Hydrophobically Impregnated Fibers
Authors: Trociński Adrian , Dziurka Dorota , Thomas Marta , Mirski Radosław
Published: September 2024

Although gypsum-based building materials exhibit many positive characteristics, solutions are still being searched for to reduce the use of gypsum or improve the physico-mechanical properties of board materials. In this study, an attempt was made to produce gypsum boards with hemp fibers. Although hemp fibers can be a specific reinforcement for gypsum-based board materials, they negatively affect the gypsum setting process due to their hygroscopic characteristics. Fibers impregnated with derivatives based on polyvinyl acetate, styrene–acrylic copolymer and pMDI (polymeric diphenylmethane diisocyanate) were used in this study. Gypsum–fiber boards produced with impregnated fibers showed approximately 30% higher mechanical properties as determined by the 3-point bending test. The positive effect of the impregnates on the hemp fibers was confirmed by FTIR (Fourier-transform infrared spectroscopy) and TG/DTA (thermogravimetric analysis/thermal gravimetric analysis) analysis.
The Development of Poly(lactic acid) (PLA)-Based Blends and Modification Strategies: Methods of Improving Key Properties towards Technical Applications—Review
Authors: Andrzejewski Jacek , Das Subhasis , Lipik Vitali , Mohanty Amar K. , Misra Manjusri , You Xiangyu , Tan Lay Poh , Chang Boon Peng
Published: September 2024

The widespread use of poly(lactic acid) (PLA) from packaging to engineering applications seems to follow the current global trend. The development of high-performance PLA-based blends has led to the commercial introduction of various PLA-based resins with excellent thermomechanical properties. The reason for this is the progress in the field of major PLA limitations such as low thermal resistance and poor impact strength. The main purpose of using biobased polymers in polymer blends is to increase the share of renewable raw materials in the final product rather than its possible biodegradation. However, in the case of engineering applications, the focus is on achieving the required properties rather than maximizing the percentage of biopolymer. The presented review article discusses the current strategies to optimize the balance of the key features such as stiffness, toughness, and heat resistance of PLA-based blends. Improving of these properties requires molecular structural changes, which together with morphology, crystallinity, and the influence of the processing conditions are the main subjects of this article. The latest research in this field clearly indicates the high potential of using PLA-based materials in highly demanding applications. In the case of impact strength modification, it is possible to obtain values close to 800 J/m, which is a value comparable to polycarbonate. Significant improvement can also be confirmed for thermal resistance results, where heat deflection temperatures for selected types of PLA blends can reach even 130 °C after modification. The modification strategies discussed in this article confirm that a properly conducted process of selecting the blend components and the conditions of the processing technique allows for revealing the potential of PLA as an engineering plastic.