bluuebunny/crossref_metadata_2025 huggingface dataset:
A Fuzzer for Detecting Use-After-Free Vulnerabilities
Authors: Zhao Xiaoqi , Qu Haipeng , Yi Jiaohong , Wang Jinlong , Tian Miaoqing , Zhao Feng
Published: November 2024

Fuzzing is an extensively used automated vulnerability detection technique. Most existing fuzzers are guided by edge coverage, which makes them less effective in detecting specific vulnerabilities, especially use-after-free (UAF) vulnerabilities. This is because the triggering of a UAF vulnerability must not only cover a specific memory operation but also satisfy a specific sequence of operations. In this paper, we propose UAF-Fuzzer for detecting UAFs, which consists of static analysis and fuzzing stages. In the static analysis stage, UAF-Fuzzer first uses target identification to determine the basic blocks that may cause UAFs as the target basic blocks; subsequently, it then instruments these target basic blocks. Subsequently, we propose a memory operation evaluation method to assess the complexity of memory operations. In the fuzzing stage, UAF-Fuzzer assigns energy to seeds using a memory evaluation operation and employs a novel seed selection algorithm to prioritize the execution of test cases that are likely to trigger UAF vulnerabilities. We designed and implemented a UAF-Fuzzer to improve the detection of UAFs and compared it with AFL, AFLFast, FairFuzz, MOPT, EcoFuzz, and TortoiseFuzz in terms of UAF vulnerability detection, crash detection, and path discovery. The results showed that UAF-Fuzzer is more effective in terms of detecting UAF vulnerabilities. We have also discovered three UAF vulnerabilities, submitted them to the software maintainer for fixing, and obtained CVE IDs.
Elevated Mortality Risk in the First Year Post-Diagnosis of Sarcoidosis: A Comprehensive Population-Based Cohort Study
Authors: Patt Yonatan Shneor , Sharif Kassem , David Paula , Hen Or , Gendelman Omer , Elizur Yoav , Ahmaro Basel , Weinstein Orly , Watad Abdulla , Amital Howard , Ben-Shabat Niv
Published: November 2024

Background and Objectives: Sarcoidosis, marked by chronic inflammation and granuloma formation, shows a variable clinical course. While many patients have benign outcomes, others face chronic, life-threatening complications. Mortality studies in sarcoidosis show mixed results due to age, ethnicity, sex, and geography, highlighting the need for a comprehensive mortality risk analysis. This study compares mortality risks between sarcoidosis patients and controls, considering demographic and clinical factors, and performs subgroup analyses across different age groups and post-diagnosis periods. Materials and Methods: This is a retrospective cohort study that used Clalit Health Services’ electronic database, including patients first diagnosed with sarcoidosis from 2000 to 2016 and age- and sex-matched controls at a 1:5 ratio. Hazard ratios (HR) for all-cause mortality were obtained using the Cox proportional hazard model, adjusted for sociodemographic and clinical variables. Results: Sarcoidosis patients showed higher mortality rates (17.7%) than controls (10.6%), with an adjusted HR of 1.79 (95% CI: 1.64–1.96, p < 0.001). Subgroup analysis revealed the HR for mortality decreased with age: HR for patients under 50 was 3.04 (95% CI: 2.20–4.21), and for those over 70, it was 1.8 (95% CI: 1.69–2.11). The HR was highest in the first year post-diagnosis. Key mortality predictors included age at diagnosis, male gender, and higher Charlson comorbidity index score. Conclusions: Sarcoidosis patients, particularly younger ones and those with higher comorbidity burdens, have elevated mortality risks compared to controls, with the highest HR in the first year post-diagnosis. These findings highlight the most vulnerable period of the disease.
Survival Outcomes of U.S. Patients with CMML: A Two-Decade Analysis from the SEER Database
Authors: Bangolo Ayrton , Amoozgar Behzad , Thapa Abhishek , Bajwa Wardah , Nagesh Vignesh K. , Nyzhnyk Yaryna , Banu Rakshanda , Bhavsar Tirth , Zhang Lili , Velichko Olga , Reddy Challa Mani Shankar , Essuman Edwina , Ibrahim Amal M. , Krishnasamy Ramkumar , Jethi Achint , Ram Arun , Haq Abdullah A. , Al hashm Abdulla Ahmad , Pathak Parna , Naeem Shafia , Gavva Rachana R. , Ratnaparkhi Prajakta H. , Samaha Paula , Espinoza Cynthia Elizabeth Armendariz , Dhakal Prasansa , Martine Frantz Ricot , Elkhidir Mogahid , Mehta Jay , Weissman Simcha
Published: November 2024

Background: Chronic Myelomonocytic Leukemia (CMML) is a rare and aggressive form of leukemia with characteristics of both myeloproliferative neoplasms (MPNs) and myelodysplastic syndromes (MDSs). This study aims to explore the clinical features, survival outcomes, and prognostic factors in CMML patients over the past 20 years using a large sample. Methods: The study data from 4124 patients diagnosed with CMML between 2000 and 2017 were sourced from the SEER database. Demographic and clinical characteristics, along with overall and cancer-specific mortality, were examined. Factors with a p-value < 0.01 in univariate Cox regression were included in the multivariate Cox model to identify independent prognostic factors, with hazard ratios (HRs) greater than one indicating adverse outcomes. Results: The majority of the cohort were male (61.57%), and most diagnoses occurred between ages 60–79 (55.16%), with a small percentage under 40 (1.41%). Non-Hispanic whites represented the largest racial group (79.03%). Multivariate analysis showed higher mortality in males, those aged 80+, residents in metropolitan areas with populations between 250,000 and 1 million, single or widowed individuals, and those who underwent chemotherapy. Conversely, lower mortality was associated with an annual income of $75,000+. Conclusions: CMML remains a rare and highly aggressive hematologic disorder. This U.S.-based retrospective cohort study identified male gender, advanced age, single or widowed status, and chemotherapy as independent poor prognostic factors. While it is expected that older patients and those requiring chemotherapy would have a poorer prognosis, the higher mortality risk in single or widowed patients, as well as males, warrants further investigation. The early involvement of family and community support may help reduce mortality in these groups, suggesting a need for larger prospective studies to explore these associations further.
Isolation and Identification of Alkaloid Genes from the Biomass of Fritillaria taipaiensis P.Y. Li
Authors: Zhou Nong , Mei Chun-Mei , Chen Fu-Gui , Zhao Yu-Wei , Ma Ming-Guo , Li Wei-Dong
Published: November 2024

Background/Objectives: Fritillaria taipaiensis P.Y. Li is a valuable traditional Chinese medicinal herb that utilizes bulbs as medicine, which contain multiple alkaloids. Biomass, as a sustainable resource, has promising applications in energy, environmental, and biomedical fields. Recently, the biosynthesis and regulatory mechanisms of the main biomass components of biomass have become a prominent research topic. Methods: In this article, we explored the differences in the heterosteroidal alkaloid components of F. taipaiensis biomass using liquid chromatography–mass spectrometry and high-throughput transcriptome sequencing. Results: The experimental results demonstrated significant differences in the eight types of heterosteroidal alkaloid components among the biomass of F. taipaiensis, including peimisine, imperialine, peimine, peiminine, ebeinone, ebeiedine, ebeiedinone, and forticine. Transcriptomic analysis revealed substantial significant differences in gene expression patterns in the various samples. Three catalytic enzyme-coding genes, 3-hydroxy-3-methylglutaryl coenzyme A synthase (HMGS), 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR), and terpene synthase (TPS), were speculated to contribute to the regulation of the differential accumulation of alkaloid synthesis in F. taipaiensis bulbs. A strong positive correlation was observed between the transcriptional level of the TPS gene and the alkaloid content of F. taipaiensis biomass, suggesting that TPS may be a key gene in the biosynthesis pathway of alkaloids. This finding can be used for subsequent gene function verification and molecular regulatory network analysis. Conclusions: This work provides fundamental data and novel insights for the subsequent research on alkaloid biosynthesis in F. taipaiensis.
Association of Liver Damage and Quasispecies Maturity in Chronic HCV Patients: The Fate of a Quasispecies
Authors: Gregori Josep , Ibañez-Lligoña Marta , Colomer-Castell Sergi , Campos Carolina , García-Cehic Damir , Quer Josep
Published: November 2024

Viral diversity and disease progression in chronic infections, and particularly how quasispecies structure affects antiviral treatment, remain key unresolved issues. Previous studies show that advanced liver fibrosis in long-term viral infections is linked to higher rates of antiviral treatment failures. Additionally, treatment failure is associated with high quasispecies fitness, which indicates greater viral diversity and adaptability. As a result, resistant variants may emerge, reducing retreatment effectiveness and increasing the chances of viral relapse. Additionally, using a mutagenic agent in monotherapy can accelerate virus evolution towards a flat-like quasispecies structure. This study examines 19 chronic HCV patients who failed direct-acting antiviral (DAA) treatments, using NGS to analyze quasispecies structure in relation to fibrosis as a marker of infection duration. Results show that HCV evolves towards a flat-like quasispecies structure over time, leading also to advanced liver damage (fibrosis F3 and F4/cirrhosis). Based on our findings and previous research, we propose that the flat-like fitness quasispecies structure is the final stage of any quasispecies in chronic infections unless eradicated. The longer the infection persists, the lower the chances of achieving a cure. Interestingly, this finding may also be applicable to other chronic infection and drug resistance in cancer.
Evaluation of the Antimicrobial Effects of Olive Mill Wastewater Extract Against Food Spoiling/Poisoning, Fish-Pathogenic and Non-Pathogenic Microorganisms
Authors: Yılmaz Dilek Kahraman , Kesbiç Fevziye Işıl , Çelik Ekrem Şanver , Odabaşı Deniz Anıl , Yilmaz Sevdan , Abdel-Latif Hany M. R.
Published: November 2024

Although antibiotics are the main therapy for bacterial infections, the reports showed that the overuse (or misuse) of antibiotics will results in several problems such as the development of antibiotic-resistant strains, persistence of drug residues, and numerous environmental concerns. Therefore, finding antibiotic alternatives is considered of vital importance. Investigation of the antimicrobial properties of several plant substances and extracts is of great value to replace antibiotics. With this objective, this study aimed to evaluate the antimicrobial activities of an ethanolic extract prepared from olive mill wastewater (OMWW), which is a by-product of olive oil production with considerable environmental burden, against 38 bacterial strains, including fish-associated pathogens, non-pathogenic isolates, collection strains, and one yeast strain, Candida albicans. Disk diffusion, minimum inhibitory concentration (MIC), and minimum bactericidal/fungicidal concentration (MBC/MFC) tests were used to determine the antimicrobial activity of the OMWWE. According to the results, OMWWE provoked strong inhibitory effects against Shewanella baltica strain SY-S145. It also showed a moderate inhibitory effect on Plesiomonas shigelloides strain SY-PS16 and Vibrio anguillarum strain SY-L24. The MIC and MBC of OMWWE on Shewanella baltica SY-S145, Vibrio gigantis strain C24, and V. anguillarum strain SY-L24 were 500 µg/mL. The MIC and MBC on V. parahaemolyticus ATCC 17802 were 1000 µg/mL, whereas the values for Aeromonas salmonicida ATCC 33658 were 500 µg/mL and 1000 µg/mL, respectively. To put it briefly, the OMWW extract showed high antimicrobial activity and can act as an environmentally friendly additive for the control and prevention of diseases caused by A. veronii, A. hydrophila, P. shigelloides, S. baltica, V. anguillarum, and V. parahaemolyticus. Its active agents also prevented infections of both fish-associated pathogens and food spoiling bacteria, which means it can not only help in the disease control mechanism but also in improving the safety of food by reduction of the microbial contamination.
Urinary Tract Infections in Kidney Transplant Patients: An Open Challenge—Update on Epidemiology, Risk Factors and Management
Authors: Pinchera Biagio , Trucillo Emilia , D’Agostino Alessia , Gentile Ivan
Published: November 2024

Urinary tract infections are one of the main complications in kidney transplant patients, with a significant impact on graft function and survival. In fact, it is estimated that up to 74% of kidney transplant patients experience at least one episode of UTIs in the first year after transplantation, with an increased risk of graft loss and an increased risk of mortality. Several risk factors have been identified, such as female gender, old age, diabetes mellitus, immunosuppression, pre-transplant UTIs, urinary tract abnormalities, and prolonged dialysis. The worsening burden of antimicrobial resistance is also in itself a risk factor and a major complication in evolution and management. The management of prophylaxis, asymptomatic bacteriuria, and UTIs is still an open challenge, with some points to be clarified. Faced with such scenarios, our review aimed to evaluate the current epidemiology, examine the risk factors, and consider all the possibilities and methods of management, giving a current view and evaluation of the topic.
The Extract of Larrea tridentata Promotes the Synthesis of Silver Nanoparticles and Stimulates Immune Responses in Penaeus vannamei Against Vibrio spp., Causing Acute Hepatopancreatic Necrosis Disease
Authors: León-Valdez Germán , Valenzuela-Quiñonez Wenceslao , Álvarez-Ruiz Píndaro , Soto-Robles Carlos A. , Nava-Perez Eusebio , López-Cervantes Gabriela , Montoya-Mejía Magnolia
Published: November 2024

Specific strains of Vibrio parahaemolyticus can cause Acute Hepatopancreatic Necrosis Disease (AHPND), a critical issue in shrimp aquaculture despite the application of several control strategies. The use of antibiotics is now restricted due to increasing bacterial resistance and overuse. Silver nanoparticles (AgNPs) have shown potential in shrimp aquaculture, with applications in boosting immunity against certain types of pathogens, promoting growth, and improving survival rates. However, an economically viable solution that protects the organisms has not been found, which is why the search for nanoparticles synthesized with plant extracts is necessary to generate environmentally friendly control strategies. In this study, we synthesized AgNPs from Larrea tridentata extract and administered them orally with feed over a 35-day period. Shrimps fed with AgNP-enriched diets showed a significant increase (p < 0.05) in mRNA expression of immune-related genes (CTL-5, MNK, SR, and GILT), particularly within the first 24–48 h. No significant differences were observed in growth rates, but survival rates in a challenge against V. parahaemolyticus exceeded 85%, higher than the control group. Based on our findings and previous literature, L. tridentata can effectively promote the synthesis of AgNPs and shows potential as an antimicrobial agent, without affecting the growth or survival of treated shrimp.
Gut Microbiome Alteration in HIV/AIDS and the Role of Antiretroviral Therapy—A Scoping Review
Authors: Gáspár Zsófia , Nagavci Blin , Szabó Bálint Gergely , Lakatos Botond
Published: November 2024

(1) Background: The gut microbiota plays a crucial role in chronic immune activation associated with human immunodeficiency virus (HIV) infection, acquired immune deficiency syndrome (AIDS) pathogenesis, non-AIDS-related comorbidities, and mortality among people living with HIV (PLWH). The effects of antiretroviral therapy on the microbiome remain underexplored. This study aims to map the evidence of the impact of integrase strand transfer inhibitors (INSTI) and non-nucleoside reverse transcriptase inhibitors (NNRTI) on the gut microbiota of PLWH. (2) Methods: A scoping review was conducted using PubMed, Web of Science, and Embase, with reports collected following PRISMA for Scoping Reviews (PRISMA-ScR). (3) Results: Evidence suggests that INSTI-based regimes generally promote the restoration of alpha diversity, bringing it closer to that of seronegative controls, while beta diversity remains largely unchanged. INSTI-based therapies are suggested to be associated with improvements in microbiota composition and a tendency toward reduced inflammatory markers. In contrast, NNRTI-based treatments demonstrate limited recovery of alpha diversity and are linked to an increase in proinflammatory bacteria. (4) Conclusions: Based on the review of the current literature, it is indicated that INSTI-based antiretroviral therapy (ART) therapy facilitates better recovery of the gut microbiome.
Metagenomic Insights into Coal Slag Remediation Effects on Soil and Microbial Health in Qinghai’s Muli Coal Mine
Authors: Lin Qi , Yang Pan , Zhang Yongbei , Zhang Wenfei , Wu Hongping
Published: November 2024

Long-term coal mining in the Muli coal mine area of Qinghai Province has degraded soil quality and reduced microbial diversity, making it imperative to implement effective ecological restoration measures to restore soil quality and enhance ecosystem functions. This study evaluated soil samples under 11 ecological restoration treatments using metagenomic sequencing combined with soil quality analysis to explore the responses of the microbial community structure and function to identify effective restoration measures. This study demonstrated that ecological restoration significantly increased the soil microbial diversity and richness, with the MLII1 (soil samples treated with a chemical weathering agent, attapulgite, and a microbial agent) and MLIII1 (soil samples treated with sheep manure (2.4 kg/m2), granular organic fertilizer (1.2 kg/m2), and the microbial agent) treatment groups performing exceptionally well. Further analysis of the functional networks revealed that although the MLII2 (soil samples treated with the chemical weathering agent and attapulgite) treatment group did not exhibit the highest species diversity, it exhibited the highest functional network complexity. The results of hierarchical clustering analysis showed that the microbial community of the MLII2 treatment group was most similar to that of the natural meadows compared to the other treatment groups. From the perspective of overall ecological restoration, this study concluded that the MLII2 treatment group exhibited the most favorable ecological restoration outcomes. This finding emphasizes the importance of not only enhancing microbial diversity but also prioritizing the restoration of community functions, especially for the recovery of fragile high-altitude ecosystems.
Differentiated Service Delivery Model in Improving HIV Treatment Outcomes Among Female Sex Workers in Gauteng Province of South Africa: A Protocol Paper
Authors: Motsieloa Lifutso , Phalane Edith , Phaswana-Mafuya Refilwe N.
Published: November 2024

South Africa developed the differentiated service delivery (DSD) model to improve access to healthcare for people living with HIV (PLHIV), especially key populations (KPs) including female sex workers (FSWs) who often face barriers in accessing HIV services. The DSD model, aims to reduce the burden on healthcare users, healthcare workers, and the healthcare system, can significantly benefit this group. However, the success of the DSD model in achieving the desired HIV treatment outcomes for FSWs has been barely evaluated. This paper describes the protocol for evaluation of the DSD model in improving HIV treatment outcomes among FSWs in Gauteng Province of South Africa. Both qualitative and quantitative methods will be utilized to address three study objectives: stakeholder analysis, mapping, and in-depth interviews (objective 1); programme evaluation of the DSD model in selected sites (objective 2); and development of a framework for optimizing the DSD model in improving HIV treatment outcomes (objective 3). Quantitative statistical analysis will be performed using STATA version 17 (College Station, TX, USA). Qualitative analysis will be performed using ATLAS.ti. This study will provide new insights into the utilization of the DSD model among FSWs in South Africa. It will also inform new strategies for the DSD model’s implementation in the country. This study will contribute towards the development of a framework for strengthening the DSD model in improving HIV treatment outcomes among FSWs in Gauteng Province.
Protective Effects of Plum on Liver and Gut Injury in Metabolic Dysfunction-Associated Fatty Liver Disease
Authors: Kim Ji-Su , Hong Sun-Mee , Kim Do-Kyun , Cho Young-Eun
Published: November 2024

Metabolic dysfunction-associated fatty liver disease (MASLD), a persistent liver condition associated with metabolic syndrome, is primarily caused by excessive fructose intake and a typical Western diet. Because there is currently only one approved treatment, lifestyle and dietary interventions are crucial. This study assessed the effects of dietary intervention involving freeze-dried plum (FDP), a natural source of antioxidants containing diverse polyphenols. This study aimed to assess its potential as a protective agent against the gut–liver axis and its therapeutic effects on liver injury and gut permeability issues associated with MASLD. We indicate that 10% FDP intake restored gut barrier proteins and reduced serum endotoxin levels in the MASLD mouse models. Additionally, 10% FDP intake significantly reduced hepatic oxidative stress, lipid metabolism, and fibrosis marker levels. Interestingly, FDP intake significantly reduced the levels of inflammatory cytokine tumor necrosis factor-α and markers of liver damage, such as serum alanine aminotransferase/aspartate aminotransferase and hepatic triglycerides. These results highlight that dietary intervention with FDP that acts as a natural antioxidant may be a significant protective and therapeutic agent against liver and gut damage caused by MASLD.
Management Patterns of Teduglutide Use in Short Bowel Syndrome: A Survey of 70 Healthcare Professionals
Authors: Harpain Felix , Milicevic Slobodan , Howard Lucy , Biedermann Patricia , Pape Ulrich-Frank
Published: November 2024

Background: This study aimed to gain real-world insights from healthcare professionals (HCPs) regarding the management of adult patients with short bowel syndrome and intestinal failure (SBS-IF) who received teduglutide and achieved parenteral support (PS) independence or PS volume stability for ≥12 months. Methods: This cross-sectional survey was conducted in five European countries and Canada via a self-reported questionnaire (November 2022–March 2023) among HCPs who manage patients with SBS-IF and who had prescribed teduglutide to ≥5 patients with SBS-IF receiving PS. Results: Of the 70 HCPs who completed the survey, almost all reported managing patients with SBS-IF who achieved PS independence or PS volume stability (99%, 69/70 and 97%, 68/70, respectively) and maintained the standard teduglutide dose, without changes. A total of 52 HCPs managed patients who achieved PS independence and discontinued teduglutide. Of these HCPs, 73% (38/52) anticipated that these patients would remain PS-independent, not requiring PS reintroduction. Of the remainder, 79% (11/14) estimated that ≤40% of these patients would require PS reintroduction. While many HCPs (81%, 42/52) would reintroduce teduglutide in patients who discontinued its use after achieving PS independence, none would do so for patients who discontinued teduglutide after achieving PS volume stability if a patient’s condition worsened. Conclusions: This survey found that patients with SBS-IF can achieve PS independence or PS volume stability with teduglutide treatment. However, some HCPs (27%, 14/52) believe that a proportion of patients discontinuing teduglutide after achieving PS independence will require PS reintroduction. This survey suggests that teduglutide treatment should continue uninterrupted, unless clinically indicated, but this requires confirmation in future studies.
Micronutrient Deficiency and Muscular Status in Inflammatory Bowel Disease
Authors: Han Joonhee , Song Hyun Joo , Kang Min Sook , Jun Hogyung , Kim Heung Up , Kang Ki Soo , Lee Donghyoun
Published: November 2024

Micronutrient deficiencies are common in inflammatory bowel disease (IBD). The aim of this study was to evaluate micronutrient deficiencies and identify muscular status of patients with IBD. From June 2019 to October 2021, a total of 105 patients with IBD were enrolled prospectively. To obtain objective data, micronutrients were measured in the patients' serum, and body composition analysis was performed using bioelectrical impedance analysis. There were 51 patients with ulcerative colitis (UC) and 54 with Crohn’s disease (CD), while the gender ratio (M: F) was 54:51. The average age was 37 ± 18 years, which was significantly lower in patients with CD than UC (29 ± 16 vs. 45 ± 16, p < 0.001). Iron and magnesium were lower in patients with CD compared to UC, respectively (63.3 ± 42.5 vs. 82.8 ± 44.0 µg/dL, p = 0.024, 2.08 ± 0.15 vs. 2.15 ± 0.19 mg/dL, p = 0.036). Vitamin D levels showed insufficiency in patients with UC and deficiency (below 20 ng/mL) in patients with CD (20.1 ± 10.6 vs. 19.0 ± 9.9 ng/mL, p = 0.567). In the UC and CD patient groups, skeletal muscle index (SMI) and adjusted skeletal muscle mass were lower in patients with CD compared to UC (SMI: 32.8 ± 4.7 vs. 35.8 ± 5.5%, p < 0.004, adjusted skeletal muscle: 7.0 ± 1.5 vs. 8.2 ± 1.9 kg/m2, p < 0.001). In conclusion, decreased trace elements, specifically iron, magnesium, and vitamin D, as well as skeletal muscle mass were observed to be prominent in patients with CD as compared to UC.
Effects of Extracted Pulse Proteins on Lipid Targets for Cardiovascular Risk Reduction: Systematic Review and Meta-Analysis of Randomized Controlled Trials
Authors: Yang Shuting , Back Songhee , Grant Shannan M. , Ayoub-Charette Sabrina , Chen Victoria , Lin Erika J. , Haintz Lukas , Chen Yue-Tong , Ahmad Elmirah , Gahagan Jacqueline , Marinangeli Christopher P. F. , Ha Vanessa , Khan Tauseef Ahmad , Mejia Sonia Blanco , Zurbau Andreea , de Souza Russell J. , Beyene Joseph , English Marcia M. , Vuksan Vladimir , Josse Robert G. , Leiter Lawrence A. , Kendall Cyril W. C. , Jenkins David J. A. , Sievenpiper John L. , Chiavaroli Laura
Published: November 2024

Background: Many clinical practice guidelines recommend dietary pulses for the prevention and management of cardiovascular disease and diabetes. The impact of extracted pulse proteins remains unclear. We therefore conducted a systematic review and meta-analysis of randomized controlled trials of the effect of extracted pulse proteins on therapeutic lipid targets. Methods and Findings: MEDLINE, Embase, and the Cochrane Library were searched through April 2024 for trials of ≥3-weeks. The primary outcome was low-density lipoprotein-cholesterol (LDL-C). The secondary outcomes were other lipid targets. Independent reviewers extracted data and assessed the risk of bias. Subgroup analyses included by pulse type and the certainty of evidence was assessed using GRADE. Results: Seven included trials (14 trial comparisons, n = 453) with a median of 4-weeks duration and dose of 35 g/day showed that extracted pulse proteins decreased LDL-C by −0.23 mmol/L (95% confidence interval: −0.36 to −0.10 mmol/L, p < 0.001). Similar effects were observed for non-high-density lipoprotein-cholesterol and apolipoprotein B. No interactions were found by pulse type. Subgroup analyses revealed effect modification by sex, with greater proportions of females seeing greater reductions. GRADE was generally moderate. Conclusions: Extracted pulse proteins likely result in moderate reductions in LDL-C and other lipid targets. Future studies on various types of extracted pulse proteins including assessments by sex are warranted.
Molecular Epidemiology of Ticks and Tick-Borne Pathogens in the Ta-Pa Mountain Area of Chongqing, China
Authors: Wang Lijun , Teng Zhongqiu , Wan Li , Wang Wen , Yuan Shan , Huang Qingzhu , Huang Juan , Zhao Na , Wang Meijia , Cao Kun , Huang Hai , Xu Jianguo , Yuan Yi , Qin Tian
Published: November 2024

To validate the prevalence and biodiversity of ticks and tick-borne pathogens in Chongqing, a total of 601 ticks were collected from dogs, cattle, and goats within the Ta-pa Mountain range in Chongqing, China. Five distinct tick species were identified, including Ixodes ovatus (1.66%, 10/601), I. acutitarsus (0.50%, 3/601), Haemaphysalis flava (10.32%, 62/601), Ha. hystricis (9.82%, 59/601), and Ha. longicornis (77.70%, 467/601). A suit of semi-nest PCR and nest PCR primers were custom-synthesized for the detection of tick-borne pathogens. The analysis yielded positive results for 7.15% Rickettsia (Candidatus R. principis, R. japonica, and R. raoultii), 3.49% Anaplasma (A. bovis and A. capra), 1.16% Ehrlichia, 1.83% Coxiella burnetii, and 3.49% protozoa (Theileria. capreoli, T. orientalis, T. luwenshuni, and Babesia sp.) in ticks. Notably, Ca. R. principis was identified for the first time in I. ovatus and Ha. longicornis. These findings underscore the significant prevalence and diversity of ticks and their associated pathogens within the Chongqing Ta-pa Mountain region. This study accordingly provides an extensive dataset that contributes to the epidemiological understanding and disease prevention strategies for tick-borne illnesses in the local area.
A Loop-Mediated Isothermal Amplification Assay Utilizing Hydroxy Naphthol Blue (LAMP-HNB) for the Detection of Treponema pallidum Subspp. pallidum
Authors: Phurijaruyangkun Saranthum , Tangjitrungrot Pongbun , Jaratsing Pornpun , Augkarawaritsawong Suphitcha , Kumkrong Khurawan , Pongparit Sawanya , Suwanvattana Pawita , Areekit Supatra , Chansiri Kosum , Santiwatanakul Somchai
Published: November 2024

Treponema pallidum subspp. pallidum is a spirochaete bacterium that causes syphilis, one of the most common sexually transmitted diseases. Syphilis progresses through four distinct stages, each characterized by specific symptoms, namely primary, secondary, latent, and late (tertiary) syphilis. Serology has been considered the primary diagnostic approach. However, it is plagued by problems such as the limited specificity of nontreponemal tests and the inadequate correlation of treponemal tests with disease activity. In this study, we focused on the development of a loop-mediated isothermal amplification assay utilizing hydroxy naphthol blue (LAMP-HNB) for the diagnosis of T. pallidum subspp. pallidum. Specifically, this study seeks to determine the analytical sensitivity (limit of detection; LOD) and analytical specificity. Four hundred clinical serum samples were analyzed for diagnostic sensitivity, specificity, and predictive value, and each technique’s 95% confidence intervals (95% CI, p < 0.05) were evaluated. The limit of detection for polymerase chain reaction with agarose gel electrophoresis (PCR-AGE), the loop-mediated isothermal amplification assay combined with agarose gel electrophoresis (LAMP-AGE), and LAMP-HNB were 116 pg/µL, 11.6 pg/µL, and 11.6 pg/ µL, respectively. Analytical specificity examinations indicated the absence of cross-reactivity with Leptospira interrogans, Staphylococcus aureus, Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, human immunodeficiency virus (HIV), and healthy human serum in PCR-AGE, LAMP-AGE, and LAMP-HNB. The diagnostic sensitivity, diagnostic specificity, positive predictive value (PPV), and negative predictive value (NPV) for PCR-AGE were 100.00 (100.00)%, 94.50 (94.40–94.60)%, 94.79 (94.69–94.88)%, and 100.00 (100.00)%, respectively. While, for LAMP-AGE and LAMP-HNB, they were 100.00 (100.00)%, 91.00 (90.87–91.13)%, 91.74 (91.63–91.86)%, and 100.00 (100.00)%, respectively. The LAMP-HNB test is simple, rapid, highly sensitive, and highly specific, without requiring expensive equipment. In the future, the LAMP-HNB assay may develop into a single-step diagnostic process, enabling the use as point-of-care testing for the diagnosis, prevention, and management of syphilis infection.
Detecting Dirofilaria immitis: Current Practices and Novel Diagnostic Methods
Authors: Pietrzak Damian , Łuczak Julia Weronika , Wiśniewski Marcin
Published: November 2024

The nematode Dirofilaria immitis is responsible for a vector-borne disease affecting canines and humans worldwide, known as cardiopulmonary dirofilariasis. An accurate and early diagnosis is of the utmost importance for effective disease management. While traditional microscopy-based methods remain invaluable, they have inherent limitations. Serological tests, in particular ELISA and immunochromatographic tests, are employed due to their capacity to detect D. immitis antigens, offering ease of use and diagnostic accuracy. The advent of molecular methods has the potential to enhance routine diagnostic approaches, with polymerase chain reaction (PCR) and real-time PCR (qPCR) becoming the most prevalent techniques. Despite not yet being integrated into routine diagnostics, which are predominantly based on the Knott’s test and serological methods, these techniques offer significant benefits in the context of scientific research. This article proceeds to examine the potential of advanced techniques, such as high-resolution melting qPCR (HRM-qPCR), loop-mediated isothermal amplification (LAMP), droplet digital PCR (ddPCR), and microRNA (miRNA) detection, which are capable of enhanced sensitivity and early detection. The following work provides an in-depth analysis of the various diagnostic methods, emphasising the necessity of the continuous improvement and adaptation of these tools to effectively combat D. immitis. The findings underscore the importance of integrating these advanced methods into routine practice to improve detection rates and outcomes for infected animals.
Oxidized Low-Density Lipoprotein Induces Reactive Oxygen Species-Dependent Proliferation of Intestinal Epithelial Cells
Authors: Gonzalez-Horta Eddy E. , Burgueno Juan F. , Leiva María J. , Villavicencio Carla , Kawaguchi Fernando I. , Hazime Hajar , Reyes Fátima , Manrique-Suárez Viana , Parra Natalie C. , Abreu Maria T. , Toledo Jorge R.
Published: November 2024

Background/Objectives: Oxidized low-density lipoprotein (ox-LDL) is a proinflammatory particle associated with various diseases and affects cell proliferation and viability in multiple cell types. However, its impact on intestinal epithelial cells remains underexplored. This study investigates the effect of ox-LDL on colonic epithelial cell proliferation and viability, as well as the underlying mechanisms involved. Methods: The expression levels of ox-LDL receptors in human colonoids were analyzed at baseline and in response to proinflammatory signals by qRT-PCR. The effect of ox-LDL on organoid proliferation was analyzed using morphometric measurements, viability assays, and the incorporation of a thymidine analog into DNA. The generation of reactive oxygen species (ROS) was determined by Amplex Red assays. Additionally, ox-LDL-induced ROS-dependent organoid proliferation was studied by exposing colonoids to an antioxidant or ROS inhibitors. Results: Colonic epithelial cells express ox-LDL receptors. Ox-LDL significantly induces the proliferation of colonic epithelial cells, which are dependent on ROS generation. Notably, ROS scavengers and NADPH inhibitors reduced ox-LDL-induced proliferation, highlighting the crucial role of oxidative stress in this process. Conclusions: This study demonstrates for the first time that ox-LDL stimulates CEC proliferation mediated by ROS production and validates that the colonic organoid model enables the analysis of potential pharmacological strategies for intestinal diseases characterized by oxidative stress and inflammation.
Multi-Target Inhibitor CUDC-101 Impairs DNA Damage Repair and Enhances Radiation Response in Triple-Negative Breast Cell Line
Authors: Seane Elsie Neo , Nair Shankari , Vandevoorde Charlot , Bisio Alessandra , Joubert Anna
Published: November 2024

Background: Since the discovery that Histone deacetylase inhibitors (HDCAi) could enhance radiation response, a number of HDACi, mainly pan-HDAC inhibitors, have been studied either as monotherapy or in combination with X-ray irradiation or chemotherapeutic drugs in the management of breast cancer. However, studies on the combination of HDACi and proton radiation remain limited. CUDC-101 is a multitarget inhibitor of Histone deacetylases (HDACs), epidermal growth factor receptor (EGFR), and human epidermal growth factor receptor 2 (HER-2). In this paper, the effectiveness of CUDC-101 in enhancing radiation response to both proton and X-ray irradiation was studied. Methods: MCF-7, MDA-MB-231, and MCF-10A cell lines were pre-treated with CUDC-101 and exposed to 148 MeV protons, and X-rays were used as reference radiation. Colony survival, γ-H2AX foci, apoptosis, and cell cycle analysis assays were performed. Results: γ-H2AX foci assays showed increased sensitivity to CUDC-101 in the MDA-MB-231 cell line compared to the MCF-7 cell line. In both cell lines, induction of apoptosis was enhanced in CUDC-101 pre-treated cells compared to radiation (protons or X-rays) alone. Increased apoptosis was also noted in CUDC-101 pre-treated cells in the MCF-10A cell line. Cell cycle analysis showed increased G2/M arrest by CUDC-101 mono-treatment as well as combination of CUDC-101 and X-ray irradiation in the MDA-MB-231 cell line. Conclusions: CUDC-101 effectively enhances response to both proton and X-ray irradiation, in the triple-negative MDA-MB-231 cell line. This enhancement was most notable when CUDC-101 was combined with proton irradiation. This study highlights that CUDC-101 holds potential in the management of triple-negative breast cancer as monotherapy or in combination with protons or X-ray irradiation.
[68Ga]Ga-FAPI-46 PET/CT for Staging Suspected/Confirmed Lung Cancer: Results on the Surgical Cohort Within a Monocentric Prospective Trial
Authors: Zanoni Lucia , Fortunati Emilia , Cuzzani Giulia , Malizia Claudio , Lodi Filippo , Cabitza Veronica Serena , Brusa Irene , Emiliani Stefano , Assenza Marta , Antonacci Filippo , Giunchi Francesca , Degiovanni Alessio , Ferrari Marco , Natali Filippo , Galasso Thomas , Bandelli Gian Piero , Civollani Simona , Candoli Piero , D’Errico Antonietta , Solli Piergiorgio , Fanti Stefano , Nanni Cristina
Published: November 2024

Background/Objectives. To evaluate T&N-staging diagnostic performance of [68Ga]Ga-FAPI-46 PET/CT (FAPI) in a suspected/confirmed lung cancer surgical cohort. Methods: Patients were enrolled in a prospective monocentric trial (EudraCT: 2021-006570-23) to perform FAPI, in addition to conventional-staging-flow-chart (including [18F]F-FDG PET/CT-FDG). For the current purpose, only surgical patients were included. PET-semiquantitative parameters were measured for T&N: SUVmax, target-to-background-ratios (using mediastinal blood pool-MBP, liver-L and pulmonary-parenchyma-P). Visual and semiquantitative T&N PET/CT performances were analysed per patient and per region for both tracers, with surgical histopathology as standard-of-truth. Results: 63 FAPI scans were performed in 64 patients enrolled (26 May 2022–30 November 2023). A total of 50/63 patients underwent surgery and were included. Agreement (%) with histopathological-T&N-StagingAJCC8thEdition was slightly in favour of FAPI (T-66% vs. 58%, N-78% vs. 70%), increasing when T&N dichotomised (T-92% vs. 80%, N-78% vs. 72%). The performance of Visual-Criteria for T-per patient (n = 50) resulted higher FAPI than FDG. For N-per patient (n = 46), sensitivity and NPV were slightly lower with FAPI. Among 59 T-regions surgically examined, malignancy was excluded in 6/59 (10%). FAPI showed (vs. FDG): sensitivity 85% (vs. 72%), specificity 67% (vs. 50%), PPV 96% (vs. 93%), NPV 33% (vs. 17%), accuracy 83% (vs. 69%). Among 217 N-stations surgically assessed (overall 746 ln removed), only 15/217 (7%) resulted malignant; FAPI showed (vs. FDG): sensitivity 53% (vs. 60%), PPV 53% (vs. 26%), NPV 97% (vs. 97%), and significantly higher specificity (97% vs. 88%, p = 0.001) and accuracy (94% vs. 86%, p = 0.018). Semiquantitative-PET parameters performed similarly, better for N (p < 0.001) than for T, slightly in favour (although not significantly) of FAPI over FDG. Conclusions: In a suspected/confirmed lung cancer surgical cohort, PET/CT performances for preoperative T&Nstaging were slightly in favour of FAPI than FDG (except for suboptimal N-sensitivity), significantly better only for N (region-based) specificity and accuracy using visual assessment. The trial’s conventional follow-up is still ongoing; future analyses are pending, including non-surgical findings and theoretical impact on patient management.
Pharmacological Activities of Zingiber officinale Roscoe: Inhibition of HSA Protein Glycation, Structure Stability and Function Restoration
Authors: Khan Mohd Wajid Ali , Sherwani Subuhi , Alshammari Muna H. E. , Alsukaibi Abdulmohsen K. D. , Khan Wahid Ali , Haque Ashanul , Alenezi Khalaf M. , Shahab Uzma
Published: November 2024

Background: Controlled non-enzymatic glycation reactions are common under normal physiological conditions. However, during elevated blood glucose conditions, the glycation reactions are accelerated, leading to the formation of toxic compounds such as advanced glycation end products (AGEs). Several natural products are now being investigated as protective agents against glycation to preserve blood protein structure and functions. Methods: Human serum albumin (HSA) was glycated with 0.05 M α-D-glucose alone or in the presence of Zingiber officinale Roscoe (ginger) extract (0.781–100 μg/mL) for 10 weeks, and biochemical, biophysical, and computational analyses were carried out. Results: HSA glycated for 10 weeks (G-HSA-10W) resulted in significant production of ketoamines, carbonyl compounds, and AGE pentosidine. Notable structural alterations were observed in G-HSA-10W, ascertained by ultraviolet (UV), fluorescence, and circular dichroism (CD) studies. Antioxidant, anti-glycating, AGEs inhibitory, and antibacterial effects of ginger extracts were observed and attributed to the presence of various phytochemicals. Molecular docking studies suggested that the compounds 8-shagaol and gingerol exhibited strong and multiple interactions with HSA. Molecular simulation analysis suggests HSA attains a high degree of conformational stability with the compounds gingerol and 8-shogaol. Conclusions: These findings showed that ginger extract has an antioxidant function and can prevent glycation-induced biochemical and biophysical alterations in HSA. Thus, aqueous ginger extract can be utilized to combat glycation and AGE-related health issues, especially diabetes, neurological disorders, inflammatory diseases, etc.
GLP-1 Receptor Agonists: A Promising Therapy for Modern Lifestyle Diseases with Unforeseen Challenges
Authors: Kupnicka Patrycja , Król Małgorzata , Żychowska Justyna , Łagowski Ryszard , Prajwos Eryk , Surówka Anna , Chlubek Dariusz
Published: November 2024

Modern lifestyle diseases remain a persistent challenge in healthcare. Currently, about 422 million people worldwide are affected by diabetes, while 1 in 8 people are living with obesity. The development of glucagon-like peptide 1 receptor agonists (GLP-1RAs) has marked a significant milestone in treating these conditions. Interest in GLP-1RAs has grown due to evidence that, beyond their established role in diabetes management, these drugs influence other metabolic disorders. This is attributed to the fact that GLP-1 receptors are found in various healthy human tissues. However, a potential cause for concern is the expression of GLP-1 receptors in certain cancers. This review focuses on the most recent findings concerning the actions of GLP-1RAs, detailing their documented impact on the thyroid gland and pancreas. It addresses concerns about the long-term use of GLP-1RAs in relation to the development of pancreatitis, pancreatic cancer, and thyroid neoplasms by exploring the mechanisms and long-term effects in different patient subgroups and including data not discussed previously. This review was conducted through an examination of the literature available in the MedLine (PubMed) database, covering publications from 1978 to 10 May 2024. The collected articles were selected based on their relevance to studies of GLP-1 agonists and their effects on the pancreas and thyroid and assessed to meet the established inclusion criteria. The revised papers suggest that prolonged use of GLP-1RA could contribute to the formation of thyroid tumors and may increase the risk of acute inflammatory conditions such as pancreatitis, particularly in high-risk patients. Therefore, physicians should advise patients on the need for more frequent and detailed follow-ups.
An Objective Evaluation Method for Image Sharpness Under Different Illumination Imaging Conditions
Authors: He Huan , Jiang Benchi , Shi Chenyang , Lu Yuelin , Lin Yandan
Published: November 2024

Blurriness is troublesome in digital images when captured under different illumination imaging conditions. To obtain an accurate blurred image quality assessment (IQA), a machine learning-based objective evaluation method for image sharpness under different illumination imaging conditions is proposed. In this method, the visual saliency, color difference, and gradient information are selected as the image features, and the relevant feature information of these three aspects is extracted from the image as the feature value for the blurred image evaluation under different illumination imaging conditions. Then, a particle swarm optimization-based general regression neural network (PSO-GRNN) is established to train the above extracted feature values, and the final blurred image evaluation result is determined. The proposed method was validated based on three databases, i.e., BID, CID2013, and CLIVE, which contain real blurred images under different illumination imaging conditions. The experimental results showed that the proposed method has good performance in evaluating the quality of images under different imaging conditions.
Composition and Effects of Aerosol Particles Deposited on Urban Plant Leaves in Terrestrial and Aquatic Habitats
Authors: Chen Siqi , Fei Fangmin , Song Yaobin , Dong Ming , Wu Aiping , Yu Hua
Published: November 2024

Plants play a vital role in mitigating aerosol particles and improving air quality. This study investigated the composition characteristics and potential effects of particles retained on the leaf surfaces of two amphibious plants (i.e., Alternanthera philoxeroides and Hydrocotyle vulgaris) in both terrestrial and aquatic habitats. The results show that plant habitats influenced the composition of aerosol particles retained on leaf surfaces. Specifically, plants in terrestrial habitats retained a higher mass concentration of coarse and large particles rich in inorganic Ca2+, accounting for over 70% of total ions, whereas plants in aquatic habitats retained a greater abundance of fine and secondary particles with high fractions of water-soluble NO3− and SO42−, taking up over 65% of total anions. Secondary particles deposited on the surfaces of plants in aquatic habitats tend to deliquesce and transform from the particle phase to the liquid phase. Terrestrial habitats facilitate the deposition of large particles. Additionally, particle accumulation on leaf surfaces adversely affected the stomatal conductance of plant leaves, leading to reductions in both the transpiration and photosynthetic rates. This study provides insights into the impact and role of plants from different habitats in mitigating urban particulate pollution.