bluuebunny/crossref_metadata_2025 huggingface dataset:
Care workers, collectivisation and protest: a case for feminist and anti-capitalist resistance against the state
Authors: Jain Dipika
Published: November 2024

Nation-wide organised protests by Accredited Social Health Activists (ASHAs), arguably the backbone of India's fragmented healthcare system, form a watershed moment in feminist protest in India by centring demands for the regularisation of their ‘voluntary’ and undercompensated work. This distinct subaltern group (the ASHAs) engages with the state through dynamic political protest. This article critically explores the protest strategies adopted by ASHAs to better understand feminist protest on the Indian political landscape. It adopts a reflexive method of inquiry by unpacking how ASHA policy perpetuates institutional patterns of gender-based occupational segregation and how ASHAs, in turn, navigate and respond to these challenges. Somewhere between victimhood and agency, ASHA workers have reclaimed a site of struggle and resistance. Indeed, in the face of gender-based discrimination, ASHA workers are agitating on their own terms. A postcolonial feminist lens allows us to explore the axes of resistance adopted by ASHAs, including their medium of protest, which offers a space for different performative strategies: the self-sustained and self-contained leadership and mobilisation in which ASHAs reject gender-based stereotypes, exclusion, disadvantage and discrimination; and the use of protest to build sites of resistance, solidarity and negotiation. This theoretical framework offers valuable insight by shifting focus away from judicial strategies and towards ASHA workers as ‘protesters’ and as authors of their own narrative.
Populist Visual Communication: A State-of-the-Art Review
Authors: Melito Francesco , Zulianello Mattia
Published: November 2024

Even though populism is arguably one of the most researched topics in contemporary political science, the study of its communication is disproportionately focused on its verbal and written dimensions. In recent years, an increasing number of studies have explored its visual dimension, highlighting its importance in the process of meaning-construction and the interaction between political actors and citizens. In this state-of-the art review, we discuss the importance of analysing visual communication and how it relates to the main approaches to the study of populism. Then, we outline the main works conducted on the visual politics of populism and suggest some potential directions for future research. The review reveals that existing research has primarily focused on the content of visual populism, highlighting, in particular, the role of images in constructing ‘the people’, ‘the enemy’ and in depicting populist leaders as ordinary yet exceptional figures. More research is needed on how images are produced and who receives and interpret them. Beyond content analysis, future research should adopt a broader range of methodological tools to fully explore populist visual communication.
Random Threshold Model: A Low-Dose Radiation-Induced Risk Assessment Approach Considering Individual Susceptibility to Cancer
Authors: Yanagawa Takashi , Fukunaga Hisanori
Published: November 2024

Objectives: The linear no-threshold (LNT) model, which has been used for radiation protection purposes, was developed based on the assumption that exposure to even a small amount of radiation may cause cancer. However, although it is known in carcinogenesis that there is variation in radiation sensitivity among individuals, the LNT model does not adequately consider radiosensitive subgroups. In this paper, we represent susceptibility to contract cancer by radiation exposure by means of the threshold of a dose-response function, introduce an assumption that the thresholds are random to represent the variation of the radiosensitivity among individuals in a susceptible subgroup. We propose a novel method, the random threshold (RT) model, for determining the safe dose limit for the subgroup to protect cancer-susceptible individuals from radiation exposure. Conclusion: The proposed method is illustrated by targeting ATM gene (a cancer-susceptible gene) mutation carriers as a radiosensitive subgroup. For cancer risk associated with low-dose radiation exposure, the contribution of radiosensitivity cannot be ignored, thus the RT model would be more suitable for risk protection for radiosensitive subgroups instead of the LNT model. We also notice that it could be widely applicable for risk protection of not only low-dose radiation but also environmental pollutants.
Patient-Clinician Communication During Cardiology Telemedicine Consultations: A Feasibility Study
Authors: Bonner Timethia J. , Noss Bryant , Hayes Sharonne N. , Ennis Katie , Warner David O. , Buckner Skye , Milam Adam J.
Published: November 2024

While studies have evaluated the utility of telehealth in replacing in-person clinical encounters, there is a dearth of literature examining the quality of patient-physician communication with telehealth encounters. Accordingly, this study assessed the feasibility of using virtual cardiology clinical encounters to examine patient-physician interaction, communication, and perceptions of the clinical encounter. Telemedicine cardiology clinical encounters were audio- and video-recorded following the encounter, patients, and cardiologists completed an electronic survey to assess perceptions of the encounter. Qualitative analysis of the communication and statistical analysis of the survey data was conducted, providing descriptive data. The study included 11 patient-physician dyads; all patients were non-Hispanic White. Cardiologists were more racially and ethnically diverse (63% Asian). Most patients agreed telemedicine was comparable to in-person encounters (85.7%), with all cardiologists reporting that patients appeared satisfied with the encounter. We utilized an assessment tool to examine patient-physician communication in the recorded virtual encounters. This study suggests examining patient-physician communication using virtual clinical encounters is feasible, although there are barriers that need addressing for larger studies.
Hybrid evolutionary algorithms  (hybrid-GAPSO) based optimization  of MIG welding process
Authors: Mallick Bijan , Hameed Azzam Sabah , Chakraborty Abhijit , Biswas Shishir Kumar , Mondal Dhiraj , Dutta Pijush
Published: November 2024

MIG welding is a modern part of advanced welding process. In this article, the mathematical modeling by ANN and parametric optimization of MIG welding joining process of cast iron has been propounded using soft computing hybrid-GAPSO. The article also shows the best model using NN basis of fittest with experimental result, computational time, convergence speed and finally RMSE obtained from cross-validation. In this research, the optimal value of the input variables obtained by hybrid-HGAPSO so that output variables hardness (HA) will be maximum & surface roughness (SR) and width of breadth thickness (WOBT) will be minimum, has been illustrated. In this experimental analysis minimized RMSE of 1.15%, 1.433%, and 1.6678% for HA, WOBT and SR are accomplished respectively by HGAPSO-ANN.
Compound 7 regulates microglia polarization and attenuates radiation-induced myelopathy via the Nrf2 signaling pathway in vivo and in vitro studies
Authors: Wu Han , Wu Jianping , Jiang Jianzhuo , Qian Zeyu , Yang Shuang , Sun Yanze , Cui Hongxia , Li Shengwen , Zhang Peng , Zhou Zhiqiang
Published: November 2024

Background

Radiation-induced myelopathy (RM) is a significant complication of radiotherapy with its mechanisms still not fully understood and lacking effective treatments. Compound 7 (C7) is a newly identified, potent, and selective inhibitor of the Keap1-Nrf2 interaction. This study aimed to explore the protective effects and mechanisms of C7 on RM in vitro and in vivo.

Methods

Western blotting, quantitative real‐time polymerase chain reaction (qRT‐PCR), reactive oxygen species (ROS) and mitochondrial polarization, terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, genetic editing techniques, locomotor functions, and tissue staining were employed to explore the protective effects and underlying mechanisms of C7 in radiation-induced primary rat microglia and BV2 cells, as well as RM rat models.

Results

In this study, we found that C7 inhibited the production of pro-inflammation cytokines and oxidative stress induced by irradiation in vitro. Further, the data revealed that radiation worsened the locomotor functions in rats, and C7 significantly improved histological and functional recovery in RM rats. Mechanically, C7 activated Nrf2 signaling and promoted the microglia transformation from M1 to M2 phenotype.

Conclusion

C7 could ameliorate RM by boosting Nrf2 signaling and promoting M2 phenotype microglia polarization in vitro and in vivo.
Effect of intravitreal injection of anti-interleukin (IL)-6 antibody in experimental autoimmune uveitis in mice
Authors: Hösel Kristin , Chasan Büsra , Tode Jan , Rose-John Stefan , Roider Johann Baptist , Ehlken Christoph
Published: November 2024

Purpose

The aim of this study was to assess the functional and clinical impact of intravitreal administration of a neutralizing anti-IL-6 antibody in the treatment of experimental autoimmune uveitis (EAU) in mice.

Methods

EAU was induced in 17 female B10.RIII mice by administering Inter-Photoreceptor-Binding-Protein (IRBP) in complete Freund’s adjuvant, followed by a boost with Pertussis toxin. Intravitreal injections of anti-Interleukin (IL)-6 antibody were administered on days 10, 13, and 16 after EAU induction (day 0) into the randomized treatment eye, with an isotype antibody similarly injected into the fellow control eye. Visual acuity was assessed using the optomotor reflex via OptoDrum, and clinical scoring was performed via fundus imaging (utilizing 6 EAU grades) in a single-blinded manner on days 0, 10, 13, 16, and 18.

Results

Uveitis developed in all 17 mice. Significantly higher visual acuity was observed in treated eyes compared to control eyes on days 13, 16, and 18. The most pronounced effect was noted on days 16 and 18 (p < 0.001). On days 13, 16, and 18 the number of eyes with lower EAU-score was significantly higher in the treatment group, with the most notable effect observed on day 18 (p < 0.003).

Conclusion

Intravitreal administration of anti-IL-6 treatment notably mitigates experimental autoimmune uveitis in mice, both functionally and clinically. Further investigations are warranted to assess the potential of intravitreal anti-IL-6 therapy as a treatment option for non-infectious uveitis in humans.
Closed-incision negative pressure wound therapy (NPWT) in elderly patients following sacral pressure sore reconstruction
Authors: Jeong Ji Won , Lee Seungkeun , Park Jun Ho
Published: November 2024

Background

Pressure sores significantly affect elderly patients, with the sacrum being especially vulnerable, often due to its proximity to the anus and potential for fecal contamination. Despite preventive measures such as frequent repositioning and specialized cushions, some sores still necessitate surgical intervention. Postoperative care focuses on monitoring, hygiene, and pressure alleviation. This study assessed the efficacy of Closed-Incision Negative Pressure Wound Therapy (CI-NPWT) for postoperative wound management in patients with sacral pressure sores treated with local flaps.

Methods

A retrospective analysis was performed on sacral sore patients who underwent reconstructive surgery from March 2019 through April 2023. Surgical procedures involved debridement and wound coverage using gluteal artery perforator-based fasciocutaneous flaps, followed by postoperative monitoring. Patients were grouped into conventional monitoring or NPWT management, with the latter utilizing the INFOV.A.C. The therapy unit was calibrated to 125 mmHg. Data on patient demographics, flap metrics, fluid drainage amounts, and six-month postoperative outcomes were collected, and then analyzed with SPSS Statistics.

Results

In this study of 52 patients with sacral pressure sores, the NPWT group (n = 25) showed significantly fewer flap complications and a lower drainage volume on the seventh postoperative day (mean 17.2 cc) compared to the conventional dressing group (mean 27.8 cc, P < 0.05). No postoperative complications were observed in the NPWT group, whereas the conventional group (n = 27) experienced one infection and three cases of dehiscence. Both groups achieved a 100% flap survival rate.

Conclusion

Closed-incision negative pressure wound therapy (CI-NPWT) shows promise in reducing wound dehiscence and infection rates in elderly patients undergoing sacral pressure sore reconstruction with local flaps. However, further research with larger, randomized studies is needed to confirm its effectiveness as an alternative to conventional postoperative care.

Trial registration.

The study was retrospectively registered by the Institutional Review Board of Seoul Metropolitan Government-Seoul National University Boramae Medical Center (No. 20–2023–25, Date: Mar. 24 2023).
Letter to Editor: a giant peritoneal loose body in the pelvic cavity
Authors: Wu Ke , Wang Qiu-Ling , Ren Wei , Guo Wu-Bin
Published: November 2024

A response to the case report by Zhang et al. and supplement another case of giant peritoneal loose body discovered due to abdominal pain. A 68-year-old man was admitted to the hospital with abdominal pain. CT revealed an ovoid mass in the pelvis measuring approximately 11.5 × 8.6 × 7.4 cm. During laparotomy, yellowish-white mass was identified within the pelvis. Histological examination revealed that the mass was hyalinized fibrous connective tissue with focal calcification. We report an extremely rare and interesting case.
Using normalisation process theory (NPT) to explore implementation of the maternal perinatal death surveillance and response (MPDSR) policy in Uganda: a reflection
Authors: Walugembe David Roger , Plamondon Katrina , Kaharuza Frank , Waiswa Peter , Wylie Lloy , Wathen Nadine , Kothari Anita
Published: November 2024

Background

The implementation of the maternal perinatal death surveillance and response (MPDSR) policy is among the envisaged strategies to reduce the high global burden of maternal and perinatal mortality and morbidity. However, implementation of this policy across various contexts is inconsistent. Theoretically informed approaches to process evaluation can support assessment the implementation of policy interventions such as MPDSR, particularly in understanding what the actors involved actually do. In this article, we reflect on how the normalisation process theory (NPT) was used to explore implementation of the MPDSR policy in Uganda. NPT is a sociological theory concerned with the social organisation of the work (implementation) of making practices routine elements of everyday life (embedding) and of sustaining embedded practices in their social contexts (integration).

Methods

This qualitative multiple case study conducted across eight districts in Uganda and among 10 health facilities (cases) representing four out of the seven levels of the Uganda health care system. NPT was utilised in several ways including informing the study design, structuring the data collection tools (semi-structured interview guides), providing an organising framework for analysis, interpreting and reporting of study findings as well as making recommendations. Study participants were purposely selected to reflect the range of actors involved in the policy implementation process. This included direct care providers located at each of the cases, the Ministry of Health and from agencies and professional associations. Data were collected using semi-structured, in-depth interviews and were inductively and deductively analysed using NPT constructs and subconstructs.

Results and conclusion

NPT served useful for process evaluation, particularly in identifying factors that contribute to variations in policy implementation. Considering the NPT focus on the agency of people involved in implementation, additional efforts are required to understand how recipients of the policy intervention influence how the intervention becomes embedded within the various contexts.
Regulation of ADAM10 activity through microdomain-dependent intracellular calcium changes
Authors: Gharzia Federico Guillermo , Aljohmani Ahmad , Beck Andreas , Philipp Stephan E. , Yildiz Daniela
Published: November 2024

A disintegrin and metalloproteinases (ADAMs) are transmembrane proteases that cleave other proteins close to the surface in a process called shedding. The prominent member ADAM10 has been linked to several pathologies such as Alzheimer’s disease, bacterial infection, cancer development and metastasis. Although the regulation of the ADAM10 activity by calcium influx and calmodulin inhibition has been reported, the spatiotemporal regulation of Ca2+-dependent ADAM10 activation and the required source of Ca2+ ions have not been thoroughly studied. In the present study, we observed the rapid Ca2+-dependent activation of ADAM10 in A549 lung carcinoma cells upon stimulation with ionomycin. The calmodulin-inhibitors trifluoperazine and ophiobolin A mediated delayed activation of ADAM10, which apparently did not depend on intracellular Ca2+ in the case of trifluoperazine. Furthermore, the surface translocation and release of ADAM10 in extracellular vesicles exhibited different kinetics and were only partially linked to catalytic activation. Finally, ADAM10 activation was observed after the entry of Ca2+ through certain channels, such as canonical members of transient receptor potential (TRP) channels. Therefore, the opening of particular channels for Ca2+ entry points and subsequent Ca2+ flux as well as the temporal aspects of the consequent increase in Ca2+ levels, must be considered for future therapeutic options involving the increasing or decreasing ADAM10 activity.
High level of aneuploidy and recurrent loss of chromosome 11 as relevant features of somatotroph pituitary tumors
Authors: Rymuza Julia , Kober Paulina , Maksymowicz Maria , Nyc Aleksandra , Mossakowska Beata J. , Woroniecka Renata , Maławska Natalia , Grygalewicz Beata , Baluszek Szymon , Zieliński Grzegorz , Kunicki Jacek , Bujko Mateusz
Published: November 2024

Background

Somatotroph neuroendocrine pituitary tumors (sPitNET) are a subtype of pituitary tumors that commonly cause acromegaly. Our study aimed to determine the spectrum of DNA copy number abnormalities (CNAs) in sPitNETs and their relevance.

Methods

A landscape of CNAs in sPitNETs was determined using combined whole-genome approaches involving low-pass whole genome sequencing and SNP microarrays. Fluorescent in situ hybridization (FISH) was used for microscopic validation of CNAs. The tumors were also subjected to transcriptome and DNA methylation analyses with RNAseq and microarrays, respectively.

Results

We observed a wide spectrum of cytogenetic changes ranging from multiple deletions, recurrent chromosome 11 loss, stable genomes, to duplication of the majority of the chromosomes. The identified CNAs were confirmed with FISH. sPitNETs with multiple duplications were characterized by intratumoral heterogeneity in chromosome number variation in individual tumor cells, as determined with FISH. These tumors were separate CNA-related sPitNET subtype in clustering analyses with CNA signature specific for whole genome doubling-related etiology. This subtype encompassed GNAS-wild type, mostly densely granulated tumors with favorable expression level of known prognosis-related genes, notably enriched with POUF1/NR5A1-double positive PitNETs. Chromosomal deletions in sPitNETs are functionally relevant. They occurred in gene-dense DNA regions and were related to genes downregulation and increased DNA methylation in the CpG island and promoter regions in the affected regions. Recurrent loss of chromosome 11 was reflected by lowered MEN1 and AIP. No such unequivocal relevance was found for chromosomal gains. Comparisons of transcriptomes of selected most cytogenetically stable sPitNETs with tumors with recurrent loss of chromosome 11 showed upregulation of processes related to gene dosage compensation mechanism in tumors with deletion. Comparison of stable tumors with those with multiple duplications showed upregulation of processes related to mitotic spindle, DNA repair, and chromatin organization. Both comparisons showed upregulation of the processes related to immune infiltration in cytogenetically stable tumors and deconvolution of DNA methylation data indicated a higher content of specified immune cells and lower tumor purity in these tumors.

Conclusions

sPitNETs fall into three relevant cytogenetic groups: highly aneuploid tumors characterized by known prognostically favorable features and low aneuploidy tumors including specific subtype with chromosome 11 loss.
The long lost denture: a rare case of an acquired, non-malignant tracheo-oesophageal fistula
Authors: Jesani Hannah , Hundle Aaron , Nankivell Paul , Kalkat Maninder
Published: November 2024

Background

Ingested dental prosthesis are susceptible to impaction in the gastrointestinal tract due to their sharp edges, size and contour. Delays in presentation arise from the lack of clear history of ingestion and misdiagnosis occurs due to the radiolucency of denture material on plain radiography. An acquired, non-malignant tracheo-oesophageal fistula (TOF) may develop from a chronically impacted denture. Surgical management of a TOF secondary to denture is a challenging clinical problem that is rarely reported in the literature and no previous case reports have described the two-staged reconstruction approach that we present here.

Case presentation

We report a case of a male in his early 60s who presented to an acute general hospital with symptoms ongoing for over one year of dysphagia, recurrent chest infections and weight loss. Barium swallow and computed tomography identified an ingested dental prosthesis (denture) that had caused a TOF. He was transferred to our specialist thoracic surgery unit where an attempt to remove the foreign body endoscopically was abandoned due to firm impaction and risk of further injury. The subsequent multi-disciplinary management of this complex case required a two-staged reconstruction approach. The first procedure involved extracting the foreign body, repairing the underlying defects with tracheal resection and anastomosis, and creating an oesophageal diversion with cervical oesophagostomy. The second procedure achieved continuity of the gastrointestinal tract with gastric pull-up and pharyngo-gastric anastomosis. Following rehabilitation, the patient was discharged on oral intake alongside percutaneous jejunostomy feeding.

Conclusions

Early recognition and removal of impacted dental prosthesis is essential to prevent morbidity and mortality. Delayed diagnosis can lead to acquired TOF with associated consequences such as recurrent pulmonary infection, mediastinitis and nutritional deficit. Challenges we encountered, such as failed attempts at endoscopic retrieval and the difficult dissection of fibrotic tissue, were directly due to the delayed identification of the denture. We highlight the importance of holding a high index of clinical suspicion of foreign body ingestion in dental prosthesis wearers who present with recurrent chest infections and ongoing dysphagia. We also promote the need for a collaborative multi-disciplinary approach in the surgical management of complex cases.
Notch1 blockade by a novel, selective anti-Notch1 neutralizing antibody improves immunotherapy efficacy in melanoma by promoting an inflamed TME
Authors: de Freitas Juliano Tiburcio , Thakur Varsha , LaPorte Kathryn M. , Thakur Vijay S. , Flores Brian , Caicedo Valentina , Ajaegbu Chioma G. E. , Ingrasci Giuseppe , Lipman Zoe M. , Zhang Keman , Qiu Hong , Malek Thomas R. , Bedogni Barbara
Published: November 2024

Background

Immune checkpoint inhibitors (ICI) have dramatically improved the life expectancy of patients with metastatic melanoma. However, about half of the patient population still present resistance to these treatments. We have previously shown Notch1 contributes to a non-inflamed TME in melanoma that reduces the response to ICI. Here, we addressed the therapeutic effects of a novel anti-Notch1 neutralizing antibody we produced, alone and in combination with immune checkpoint inhibition in melanoma models.

Methods

Anti-Notch1 was designed to interfere with ligand binding. Mice were immunized with a peptide encompassing EGF-like repeats 11–15 of human Notch1, the minimal required region that allows ligand binding and Notch1 activation. Positive clones were expanded and tested for neutralizing capabilities. Anti-Notch1-NIC was used to determine whether anti-Notch1 was able to reduce Notch1 cleavage; while anti-SNAP23 and BCAT2 were used as downstream Notch1 and Notch2 targets, respectively. K457 human melanoma cells and the YUMM2.1 and 1.7 syngeneic mouse melanoma cells were used. Cell death after anti-Notch1 treatment was determined by trypan blue staining and compared to the effects of the gamma-secretase inhibitor DBZ. 10 mg/kg anti-Notch1 was used for in vivo tumor growth of YUMM2.1 and 1.7 cells. Tumors were measured and processed for flow cytometry using antibodies against major immune cell populations.

Results

Anti-Notch1 selectively inhibited Notch1 but not Notch2; caused significant melanoma cell death in vitro but did not affect normal melanocytes. In vivo, it delayed tumor growth without evident signs of gastro-intestinal toxicities; and importantly promoted an inflamed TME by increasing the cytotoxic CD8+ T cells while reducing the tolerogenic Tregs and MDSCs, resulting in enhanced efficacy of anti-PD-1.

Conclusions

Anti-Notch1 safely exerts anti-melanoma effects and improves immune checkpoint inhibitor efficacy. Thus, anti-Notch1 could represent a novel addition to the immunotherapy repertoire for melanoma.
Nepali oral microbiomes reflect a gradient of lifestyles from traditional to industrialized
Authors: Ryu Erica P. , Gautam Yoshina , Proctor Diana M. , Bhandari Dinesh , Tandukar Sarmila , Gupta Meera , Gautam Guru Prasad , Relman David A. , Shibl Ahmed A. , Sherchand Jeevan Bahadur , Jha Aashish R. , Davenport Emily R.
Published: November 2024

Background

Lifestyle plays an important role in shaping the gut microbiome. However, its contributions to the oral microbiome remain less clear, due to the confounding effects of geography and methodology in investigations of populations studied to date. Furthermore, while the oral microbiome seems to differ between foraging and industrialized populations, we lack insight into whether transitions to and away from agrarian lifestyles shape the oral microbiota. Given the growing interest in so-called “vanishing microbiomes” potentially being a risk factor for increased disease prevalence in industrialized populations, it is important that we distinguish lifestyle from geography in the study of microbiomes across populations.

Results

Here, we investigate salivary microbiomes of 63 Nepali individuals representing a spectrum of lifestyles: foraging, subsistence farming (individuals that transitioned from foraging to farming within the last 50 years), agriculturalists (individuals that have transitioned to farming for at least 300 years), and industrialists (expatriates that immigrated to the USA within the last 20 years). We characterize the role of lifestyle in microbial diversity, identify microbes that differ between lifestyles, and pinpoint specific lifestyle factors that may be contributing to differences in the microbiomes across populations. Contrary to prevailing views, when geography is controlled for, oral microbiome alpha diversity does not differ significantly across lifestyles. Microbiome composition, however, follows the gradient of lifestyles from foraging through agrarianism to industrialism, supporting the notion that lifestyle indeed plays a role in the oral microbiome. Relative abundances of several individual taxa, including Streptobacillus and an unclassified Porphyromonadaceae genus, also mirror lifestyle. Finally, we identify specific lifestyle factors associated with microbiome composition across the gradient of lifestyles, including smoking and grain sources.

Conclusion

Our findings demonstrate that by studying populations within Nepal, we can isolate an important role of lifestyle in determining oral microbiome composition. In doing so, we highlight the potential contributions of several lifestyle factors, underlining the importance of carefully examining the oral microbiome across lifestyles to improve our understanding of global microbiomes.
Identification of powdery mildew resistance quantitative trait loci in melon and development of resistant near-isogenic lines through marker-assisted backcrossing
Authors: Wang Chun-San , Lin Ssu-Yu , Huang Jin-Hsing , Chang Hsin-Yi , Lew Di-Kuan , Wang Yu-Hua , Hwu Kae-Kang , Huang Yung-Fen
Published: November 2024

Background

Melon (Cucumis melo L.), an important cucurbit crop, faces production limitations due to powdery mildew (PM). Developing resistant varieties offers a sustainable, genetics-based alternative to chemical treatments. Therefore, identifying PM resistance quantitative trait loci (QTL) and creating trait-associated markers are essential for efficient melon PM resistance improvement through marker-assisted backcrossing (MABC).

Results

Three F2 populations, A6, B2, and C4, were generated for QTL mapping of PM resistance. Major QTL were identified on chromosome 2 in A6, chromosome 5 in B2, and chromosomes 5 and 12 in C4. A series of TaqMan® assays targeting regions on chromosomes 2, 5, and 12 were developed and validated for foreground and recombinant selection, complemented by the double digest restriction-site associated DNA genotyping system to evaluate the recurrent parent genome recovery. Three MABC programs using resistant donor parents from A6 and C4 crossed with elite susceptible recurrent parents with green and orange fruit flesh were implemented. After two to three cycles of MABC, individual QTL was successfully introgressed into elite genetic backgrounds, giving six PM resistance lines in each green- and orange-fleshed background. PM inoculation on the twelve near-isogenic lines confirmed their resistance to PM.

Conclusions

We have identified major PM resistance QTL for melon on chromosomes 2, 5, and 12 and have introgressed individual QTL to elite genetic backgrounds using MABC in three and a half years. This study demonstrates the power of combining high-throughput genotyping with breeding efforts and showcases the efficiency of molecular breeding.
Dysbiosis of oral bacteria in patients with chronic kidney disease
Authors: Yasuno Tetsuhiko , Tada Kazuhiro , Takahashi Koji , Watanabe Maho , Ito Kenji , Arima Hisatomi , Masutani Kosuke
Published: November 2024

Background

Oral bacteria are altered in patients with diabetes, cardiovascular diseases, and cancer. However, the oral microbiome of patients with chronic kidney disease (CKD), including those receiving renal replacement therapy, remains unclear. Here, we report changes in the oral microbiome of patients with CKD.

Methods

In total, 103 individuals were recruited for this study, including 46 with stages 3–5 and 22 with stage 5D CKD, including those receiving renal replacement therapy (CKD group), and 35 with CKD stages 1–2. The oral microbiome composition was analyzed using a 16S ribosomal RNA gene-based sequencing protocol.

Results

At the genus level, the periodontal pathogens Tannerella, Fusobacterium, and Capnocytophaga were more abundant in the CKD group (stages 3–5) than in the control group (linear discriminant analysis score > 3). Streptococcus, which has been shown to be involved in dental plaque formation, and Capnocytophaga were abundant in the CKD group (stage 5D). The unweighted UniFrac distance revealed a separation trend among CKD stages 1–2, 3–5, and 5D groups (stages 1–2 versus 3–5: P = 0.137. ; stages 3–5 versus 5D: P = 0.002). As the CKD stage progressed, the number of bacteria with significant differences qualitative and quantitative changes were observed in the β-diversity assessment.

Conclusions

Our findings highlight that periodontal disease bacteria increased in the CKD (stages 3–5 and 5D) group, including those receiving renal replacement therapy.
Poloxamer®s anchored with TAT enhance blood–brain barrier penetration of carbamazepine for the treatment of epilepsy: an in vivo study
Authors: Sotoudegan Farnaz , Amini Mohsen , Sharifzadeh Mohammad , Samadi Nasrin , Sotoudegan Farzaneh
Published: November 2024

Carbamazepine is a pharmacological medication commonly prescribed to treat epilepsy. Dose adjustments, poor bioavailability, and prolonged side effects present significant challenges associated with its use. Poloxamer micelles have demonstrated exceptional properties as nanocarriers for drug delivery. This research aimed to develop Poloxamer nanomicelles containing carbamazepine and assess their potential to cross the blood–brain barrier.

Poloxamer 407 and P-85 micelles, anchored with TAT as a ligand and containing carbamazepine, were prepared. The morphology, entrapment efficiency, drug release, stability, and toxicity of nanomicelles were examined, along with animal studies conducted to evaluate their anticonvulsant effects. The distribution of carbamazepine-Poloxamer in the brain and plasma was assessed.

The results indicated the successful formation of spherical nanomicelles with an average size of less than 100 nm, and carbamazepine was effectively incorporated into the micelles. Formulations composed of mixtures of Poloxamer exhibited a high encapsulation efficiency of approximately 92.1% and remained stable for three months. A sustained release of carbamazepine was observed for up to 72 h. The anticonvulsant effect of carbamazepine-loaded nanomicelles in mice was found to be significantly greater than that of those treated with carbamazepine solution, with the effect increasing by approximately tenfold. Compared to free carbamazepine, the carbamazepine-loaded nanomicelles exhibited a 5.5-fold increase in the brain targeting index, with no toxicity observed in mice treated with these nanomicelles. These findings suggest that Poloxamer micelles represent a promising nanoscale, controlled-release delivery system that is free from toxicity and can enhance the penetration of carbamazepine into the brain while improving its anticonvulsant activity.

Graphical Abstract
Trends and inequalities in the use of deworming medication during pregnancy in Sierra Leone, 2008–2019
Authors: Osborne Augustus , Bai-Sesay Alpha Umaru , Tommy Alieu , Bangura Camilla , Ahinkorah Bright Opoku
Published: November 2024

Background

Intestinal worm infections are a significant public health concern for pregnant women in low- and middle-income countries. These infections can lead to anaemia, malnutrition, and adverse pregnancy outcomes, including premature birth and low birth weight. Deworming medication during pregnancy is a safe and effective strategy to prevent these complications and improve maternal and child health. This study aims to investigate the trends and inequalities in the use of deworming medication during pregnancy among women in Sierra Leone between 2008 and 2019.

Methods

The study utilised data from the Sierra Leone Demographic Health Surveys conducted in 2008, 2013, and 2019. We used the Health Equity Assessment Toolkit developed by the World Health Organisation to calculate various measures of inequality, including difference, ratio, population attributable risk, and population attributable fraction. An inequality assessment was conducted for five stratifiers: age, economic status, level of education, place of residence, and sub-national province.

Results

The prevalence of deworming medication during pregnancy was 43.8% in 2008, 72.4% in 2013, and 83.5% in 2019 in Sierra Leone. There was a decrease in age-related inequality from a difference of 3.7% in 2008 to −0.8% in 2019. Economic-related inequality increased from a difference of −8.5% in 2008 to −8.2% in 2019. Both population attributable fraction and population attributable risk were zero in all survey years for economic status, indicating no improvement in the setting average without economic-related inequality. Inequality in education increased from a difference of -8.9% in 2008 to −8.4% in 2019 and decreased from a difference of −2.6% in 2008 to –5.5% in 2019 for place of residence. Provincial inequality decreased from a difference of 29.5% in 2008 to 11.8% in 2019. The population attributable risk for province reveals that the setting average could have been 10.5 percentage points lower in 2008, 8.2 percentage points lower in 2013, and 5.9 percentage points lower in 2019 without provincial inequality.

Conclusion

The prevalence of deworming medication use during pregnancy substantially increased from 2008 to 2019 (43.8% to 83.5%) in Sierra Leone. This suggests a positive public health trend in maternal healthcare access and education. Inequalities related to economic status and education increased slightly while age-related, place of residence and provincial inequalities decreased. This indicates an inequitable distribution of this essential healthcare intervention across these stratifiers. The government and policymakers should continue efforts to raise awareness and promote the use of deworming medication during pregnancy.
Rauvolfia vomitoria phenol extract relieves pentylenetetrazol-induced seizures in Swiss mice and protects some temporal lobe structures
Authors: Ekong Moses B. , Bassey Okokon O. , Ebeh Deborah I. , Usukuma Godslove D. , Samuel Darlington C. , Bassey Rosemary B. , Peter Aniekan I. , Mbadugha Christopher C. , Okokon Jude E. , Akpanabiatu Monday I.
Published: November 2024

Background

Rauvolfia vomitoria (R. vomitoria) is a plant of economic importance due to its diverse ethnomedicinal properties, including the anticonvulsant effect. In this study, we studied the antiseizure and neuroprotective potentials of R. vomitoria extracts against pentylenetetrazol (PTZ)-induced kindling.

Methods

Twenty-five adult Swiss mice (25–30 g) were assigned to five groups (n = 5): control group, PTZ treatment group, and PTZ treatment after receiving oral R. vomitoria crude extract (100 mg/kg), R. vomitoria phenol extract (50 mg/kg) or sodium valproate (15 mg/kg) every 48 h for 28 days. Seizure scores, cognitive behavioral tests including novel object test, Y-maze test, and the elevated plus maze test, as well as brain neurochemicals and histomorphology studies, were performed.

Results

Compared with the control group, the PTZ group showed comparable body weight and durations in closed and open arms (P > 0.05), but preference for familiar objects, significant (P < 0.05) spontaneous alternation, increased monoamine oxidase activity and nitric oxide level, and Nissl chromatolysis in the temporal lobe structures including the cortex, hippocampus, and amygdala. R. vomitoria phenol extract pretreatment significantly (P < 0.05) reduced seizures, prevented adverse cognitive behaviors, decreased the nitric oxide level, and reduced the temporal lobe Nissl chromatolysis compared with the R. vomitoria crude extract pretreatment group and the sodium valproate pretreatment groups.

Conclusions

Thus, R. vomitoria phenol extract showed promising results against seizures and potential for general brain protection, suggesting that the anticonvulsant property of R. vomitoria may be attributed to its phenol constituent. More studies are needed to delineate the mechanisms of its action.
Simplified magnetic resonance index of activity score versus simple endoscopic score in Crohn's disease: prospective study
Authors: Hassan Nada Saad Mohamed Saad , Moghazy Khaled Mohamed Mourad , Salem Osama Ebada , Afifi Ahmed Hafez , Emara Doaa Mohamed , Mohamed Mohamed Masoud Radwan
Published: November 2024

Background

To evaluate the correlation between simplified MR index of activity (sMaRIA) score and simple endoscopic score (SES-CD) in Crohn's disease activity assessment. A prospective study was done on established Crohn's disease patients referred to our institution. Magnetic resonance enterography and colonoscopy were performed as an activity assessment protocol searching for activity signs through calculation of sMaRIA score and SES-CD score and correlation between them. One hundred patients were enrolled in the study in period from July 2021 to July 2022. Patients with isolated upper gastrointestinal Crohn's disease (n = 4) or performed surgery before completion of activity assessment protocol (n = 9) or dropout (n = 18) were excluded. Patients with any age group, with ileal or colonic or ileo-colonic Crohn's disease and completed the protocol were eligible for the study (n = 69).

Results

Sixty-nine patients with 345 bowel segments (five segments for each patient: ileum, right colon, transverse colon, left colon/sigmoid and rectum) were completely evaluated: 33 males and 36 females with mean age 29.16 ± 11.37 years. sMaRIA and SES-CD scores were calculated for each patient (global), and each bowel segment showed 97.50% sensitivity and 79.31% specificity at the level of global scores as well as significant positive correlation between the two scores at patient level/overall segments (rs = 0.816, p < 0.001), at ileal segments (rs = 0.704, p < 0.001) and colonic segments (right colon rs = 0.661, p ≤ 0.001, transverse colon rs = 0.586, p ≤ 0.001, left colon rs = 0.731, p < 0.001 and rectum rs = 0.786, p < 0.001). There were good inter-rater agreement between the two radiologists for the three parameters (wall thickness > 3 mm, mural edema and fat stranding) and moderate for mucosal ulcer detection with k value 0.666, 0.712, 0.712 and 0.565, respectively.

Conclusions

sMaRIA score is considered to be a reliable tool for Crohn's disease activity evaluation as compared to SES-CD.
Comparative study between effect of preoperative multimodal analgesia and pregabalin as unimodal analgesia in reduction of postoperative opioids consumption and postoperative pain in laparoscopic cholecystectomy
Authors: Kamal Yassmin M. , Wahsh Engy A. , Abdelwahab Hisham A. , ElBaz Walied A. , Hussein Hazem A. , Rabea Hoda M.
Published: November 2024

Background

Laparoscopic cholecystectomy is a popular abdominal surgery and the most common problem for patients undergoing laparoscopic cholecystectomy is the postoperative pain, and associated side effects due to opioids use for pain management and multimodal analgesia is suggested to reduce postoperative pain and need for postoperative opioids. This controlled clinical trial compares the effects of multimodal analgesia and pregabalin as unimodal analgesia on postoperative pain management, postoperative opioids consumption, and reduction of opioids accompanied adverse effects in patients undergoing laparoscopic cholecystectomy where large multicenter studies evaluating specific analgesic combinations are lacking.

Method

This comparison randomized controlled trial between multimodal analgesia approach and pregabalin as unimodal analgesia included 95 laparoscopic cholecystectomy patients that were randomly allocated to three groups using a simple randomization method where multimodal and pregabalin groups included 30 patients in each and the drugs was administered orally one hour before the incision and control group included 35 patients that did not receive any preoperative analgesia. Multimodal analgesic therapy included acetaminophen 1 g, pregabalin 150 mg and celecoxib 400 mg while pregabalin group received pregabalin 150 mg only.

Results

Multimodal group showed a significantly lower need for total opioid analgesics mean ± SD (1.33 ± 1.918) as compared to the control group mean ± SD (3.31 ± 2.784) with p-value 0.014. Pregabalin and multimodal groups showed significantly lower postoperative visual analogue scale used for pain assessment mean ± SD (3.50 ± 2.543) and mean ± SD (3.70 ± 2.231), respectively, compared to the control group mean ± SD (5.89 ± 2.857) with p-value 0.001.

Conclusion

Multimodal analgesia reduced postoperative opioids consumption more than pregabalin alone when used preoperatively in laparoscopic cholecystectomy and consequently reduced opioids associated adverse effects, but they have the same efficacy in reducing postoperative pain, so pregabalin can be used alone preoperatively in patients with contraindications for using some analgesics included in multimodal analgesia protocol. The study was registered retrospectively in clinical trials; Trial registration ID: NCT05547659.
The potential therapeutic role of Lisinopril in augmenting the striatal neuroplasticity via the striatal ACE2/Ang1-7/MAS receptor axis in 3-nitropropionic acid-induced Huntington’s disease in rats: shifting paradigms in Huntington’s disease treatment
Authors: Wanas Hanaa , Rabie Mostafa Adel , Aboulhoda Basma Emad , Ramadan Nagwa Mahmoud , Abdelwahab Sahar , Abdallah Sara Sayed Kadry , Ali Eid Nassar , Khayruddeen Leyan Nasruddeen , Elhassan Yasir Hassan , Alghabban Hadel Mahroos , Abdelsalam Shaimaa Mohamed , Khalifa Amira Karam
Published: November 2024

Background

The exact pathogenesis of Huntington’s disease (HD) remains unclear. However, mitochondrial dysfunction and oxidative stress are supposed to play a significant role. The objective of this study was to examine the possible neuroprotective effect of Lisinopril (Lisino) in a 3-nitropropionic acid-produced HD in rats.

Methods

Sixty-four rats were divided into four groups (16/group): Group (1): Normal control group, Group (2): Lisinopril control group, Group (3): 3-NP non-treated group, and Group (4): (3-NP + Lisinopril) group. Behavior assessments (open field test, rotarod test, grip strength test) were performed along with different histological and biochemical parameters.

Results

Lisinopril upregulated the expression of the ACE2/Ang1-7/MAS receptor (MasR) axis of RAS, which triggered the PI3K/Akt pathway and prompted the CREB/BDNF neurogenesis signal. Furthermore, Lisinopril remarkably downregulated the inflammatory cytokines (NF-κB, TNF-α, IFN-γ and IL-6), decreased apoptotic markers (p53, BAX/Bcl2 ratio, Cyt-c and caspase-3) and upgraded the mitochondrial TFAM content and SDH activity along with restoration of the redox mechanism by recovering SOD, catalase, GSH and Nrf2.

Conclusion

Notably, the outcomes of this study disclosed that Lisinopril could be a future neuroprotective therapeutic candidate against HD.
A fast prediction method of fatigue life for crane structure based on Stacking ensemble learning model
Authors: Zhao Jincheng , Dong Qing , Xu Gening , Li Hongjuan , Lu Haiting , Zhuang Weishan
Published: November 2024

To quickly obtain the fatigue life of cranes in service, the metal structure that determines the crane life is anchored. Meanwhile, the fast prediction method of fatigue life of crane metal structures based on the Stacking ensemble learning model is proposed. Firstly, in line with the structural stress method, the global rough model of the metal structure is established by the co-simulation technology to obtain the fatigue damage regions of the structure. The local fine model is constructed by local cutting and boundary condition transplantation to determine the critical weld at the failure regions. Secondly, through weld definition, equivalent structural stress acquisition, and fatigue life calculation, the sample data set with lifting load and trolley running position as input and fatigue life cycle times as output is constructed. Then, the Stacking integrated learning model combining gradient boosting, ridge regression, Extra Trees, and linear is built. On this basis, combined with the Miner theory, the rapid prediction of crane fatigue life is realized. Finally, the proposed method is applied to the QD40t × 22.5 m × 9 m general bridge crane. The results show that the life sample set constructed by the structural stress method is more accurate and reasonable than the nominal, hot spot, and fracture mechanics methods. The life prediction results of the Stacking integration model were improved by 6.3 to 49.2% compared to the single model. The method has theoretical and practical significance in reducing accidents and ensuring the safe operation of cranes.