bluuebunny/crossref_metadata_2025 huggingface dataset:
A Critical Discourse Analysis of Feminine and Masculine Identity in August Wilson’s Pittsburg Cycle
Authors: Torki Baghbaderani Fatemeh
Published: December 2024

In his collection of ten plays, The Pittsburg Cycle, August Wilson (1945-2005) presents the social dynamism of African Americans across the twentieth century America. In his plays, many newly freed African slaves move to the North, hoping to shape their identity as respectable citizens of great worth. They are, however, reckoned as foreigners in a new habitus. Since they have lost contact with their past heritage and have no access to their social codes as a source of power, they search for means through which they can concretize the song they carry within themselves as a sign of their true African heritage. Through the theory of critical discourse analysis, this article focuses on Michel Foucault’s theory of discourse to study, analyze, and compare the discourse of both male and female characters of the plays. According to the age-old western tradition, male discourse represents power, assurance, and certainty in contrast to female discourse imbued with characteristics opposite to the mentioned ones. This article aims to explore how Wilson subverts the male and female discourse to create a nongendered African soul, who embodies characteristics of both sexes.
Assessing speaking proficiency of English teachers through self-assessment test: East Wollega zone in focus
Authors: Baisa Girma Abate , Worabu Rufael Disasa , Belachew Teshale Tefera
Published: December 2024

This study addresses the significant role of English speaking proficiency in the teaching-learning process, particularly considering the questionable speaking abilities of English teachers. The research aims to assess the speaking proficiency of English teachers in the East Wollega Zone. Employing a convergent parallel mixed design, blending quantitative and qualitative data methods, self-assessment tests, and classroom observations were utilized for data collection, and 101 participants for self-assessment and 15 respondents for classroom observations were selected using simple random sampling method. Findings indicate a prevalent trend of low speaking proficiency among English teachers, supported by both self-assessment data (mean= 2.3, standard deviation= 0.62) and classroom observation records. While gender did not significantly influence self-assessment scores, significant differences were noted among education qualification levels and teaching experience groups. Multiple regression analysis revealed a moderate association (R2= 44.1%) between independent and dependent variables. The study concludes with implications underscoring the urgent need to enhance English teachers’ speaking competency, particularly in first-cycle primary schools in the East Wollega Zone, emphasizing the potential to elevate the quality of the teaching-learning process and improve students' language acquisition and overall educational outcomes.
Discovering the power of Discord: Members’ experiences and their performances in learning English
Authors: Sufi M. Iqbal Farabi , Afrida Nina , Meutia Cut Intan , Daulay Sholihatul Hamidah
Published: December 2024

Discord has experienced a recent surge in its utilization for educational purposes. Numerous communities have embraced Discord servers as a means to foster and support learning activities. Many studies discuss Discord in learning English, but there is a lack of extensive academic research focusing on a member’s experiences in using Discord. Most studies on broader online language learning communities and other digital platforms, but only a few studies investigate Discord application from an overview of this phenomenon, this study aimed to determine how the members’ experience in using the Discord application as contributed to facilitating English learning and to describe the performances of Discord in fostering English. a qualitative method with a phenomenological study applied in this research. twenty members who have been using Discord for a year and more than a year and are interested in learning English became the sample by purposive random sampling. Data was gathered from unstructured interviews and participant observation online. The results from the observation demonstrated that the efficacy of Discord can be seen from the function of features, it supports English online learning through seven crucial features that users can leverage: voice channels, text channels, direct messages, screen sharing, resource sharing, bot integrations, and notifications and reminders. Data from the interview showed members’ experiences said Discord can help them in mastering English. As a result, the implications of the research can guide the development of more effective, engaging, and inclusive Discord-based learning communities, ultimately enhancing the overall learning experience and outcomes for participants.
Acute mortality event in false pilchards Harengula clupeola after salinomycin and amprolium treatment for myxozoan (Enteromyxum leei) infection
Authors: Farmer K , Perry SM , Meredith A , Woodyard ET , Rosser TG , Stilwell JM , Delaune AJ
Published: December 2024

This report documents complications in false pilchard Harengula clupeola and scad Decapterus macarellus associated with a salinomycin (60 mg kg-1) and amprolium (100 mg kg-1) gel feed treatment, along with prolonged temperature increase, for an Enteromyxum leei outbreak in a salt water, mixed species, public aquarium exhibit. Shortly after administration, a mass mortality event ensued where hundreds of false pilchards and a few scad died. Medicated gel feed was noted within the gastrointestinal tracts of all affected fish. Microscopic lesions consistently involved myodegeneration and necrosis of the gastric muscularis layer and myocardium. Salinomycin was detected in multiple tissues while amprolium was largely limited to the stomach. Based upon the clinical, pathological, and toxicologic findings, the mortality event was attributed to salinomycin toxicity. False pilchards and scad were the only species affected, suggesting a species-specific sensitivity.
Asuhan Keperawatan Jiwa Pasien Defisit Perawatan Diri dengan masalah Personal Hygiene menggunakan terapi Token Ekonomi
Authors: Kesuma Rafika Putri , Nauli Fathra Annis , Nelma Ulia
Published: December 2024

Terapi token ekonomi merupakan terapi prilaku dengan penerapan memberikan reward pada pasien yang dapat meningkatkan kebersihan diri. Beberapa penelitian terkait terapi token ekonomi untuk meningkatkan kemampuan kebersihan diri sudah banyak terbukti keefektifannya. Pentingnya penelitian ini dilakukan untuk menganalisis asuhan keperawatan pada pasien defisit perawatan diri  dengan masalah personal hygiene. Terapi ini diberikan secara tatap muka pada Tn. F (33 tahun) dan Tn. A (28 tahun) selama 7 hari dengan frekuensi 1 kali sehari dengan waktu 30 menit. Ners muda juga mengobservasi kegiatan harian yang sudah dijadwalkan dan menggunakan instrumen observasi defisit perawatan diri (PPNI, 2018). Hasil setelah implementasi yang dilakukan terdapat peningkatan pemahaman serta mampu melakukan perawatan diri seperti kegiatan mandi, menggosok gigi, potong kuku, berpakaian, eliminasi, dan cara makan yang baik dan benar. Pada pasien I dengan nilai skor rata-rata pre test yaitu 16.71 dan nilai skor rata-rata post test yaitu 17.85. Dan pada Tn. A didapatkan nilai skor rata-rata pre test yaitu 13.28 dan nilai skor rata-rata post test yaitu 15. Berdasarkan hasil penerapan asuhan keperawatan ini disarankan kepada perawat jiwa dapat mengintervensikan terapi token ekonomi ini dalam penatalaksanaan pasien dengan defisit perawatan diri.
Beyond the glass ceiling, more 'housework'? Womens' work assignment, performance and influence in political institutions
Authors: Boulaziz Louisa
Published: December 2024

Women remain under-represented in many political institutions. To what extent does the under-representation of women impact their performance, and the amount influence they have within political institutions? I argue that women have a harder time getting (s)elected because of gender-based selection bias and that those women who are (s)elected perform, on average, better than their male counterparts. Yet, women have less influence because gender-based selection bias may also exist within the institutions to which women have been (s)elected to serve. I empirically assess my argument in the context of the Court of Justice of the European Union. I find that women judges are assigned the judicial “housework”, while male judges are assigned the groundbreaking cases, resulting in a gender gap in influence. Yet, my results also show that women perform on average better than their male counterparts and complete their cases faster.
Pneumococcal carriage in a large Sicilian sample population: impact on the current epidemiological scenario and implications for future vaccination strategies
Authors: Amodio Emanuele , Tramuto Fabio , De Francisci Valerio , Genovese Dario , Guzzetta Valeria , Pisciotta Vincenzo , Santino Arianna , Randazzo Giulia , Trapani Giulio , Vella Giuseppe , Vitale Francesco
Published: December 2024

Introduction

Streptococcus pneumoniae is a prevalent and virulent global pathogen, with colonization being considered a precondition for pneumococcal disease. Understanding colonization is critical for gaining insights into transmission dynamics and developing effective interventions. This study aimed to determine the prevalence of nasopharyngeal colonization and serotype distribution in the Sicilian population.

Methods

Observational study randomly selecting samples belonging to Sicilian individuals whose nasopharyngeal swabs were collected between February 1, 2020, and December 31, 2022. Pneumococcal colonization was determined using PCR for the pneumococcal autolysin (LytA) gene, and positive samples were serotyped.

Results

The study sample consisted of 1,196 individuals, with 17.4% testing positive for the LytA gene. Pneumococcal colonization rates fell from birth to 24 years, with a peak in 0-4-year-olds (aOR=6.9; p<0.001). Colonization was higher in colder months, particularly in December (aOR=2.9, p<0.05) and February (aOR=4, p<0.05). Serotypes 22F and 24ABF exhibited strong colonization and an invasive pneumococcal disease (IPD) risk, whereas serotypes 4, 6AB, 9VA, and 13 had high colonization but a low IPD risk. Serotypes 3 and 8 exhibited considerable IPD risk but low colonization.

Conclusion

Our findings provide insights into pneumococcal colonization mechanisms, influencing serotype prevalence, colonization risk variables, and serotype comparisons for colonization and pathogenicity propensity.
Assessing the impact of gut microbiota and metabolic products on acute lung injury following intestinal ischemia-reperfusion injury: harmful or helpful?
Authors: Wang Qiong , Yu Zi-Hang , Nie Liang , Wang Fei-Xiang , Mu Guo , Lu Bin
Published: December 2024

Ischemia-reperfusion injury (IRI) is a common and clinically significant form of tissue damage encountered in medical practice. This pathological process has been thoroughly investigated across a variety of clinical settings, including, but not limited to, sepsis, organ transplantation, shock, myocardial infarction, cerebral ischemia, and stroke. Intestinal IRI, in particular, is increasingly recognized as a significant clinical entity due to marked changes in the gut microbiota and their metabolic products, often described as the body’s “second genome.” These changes in intestinal IRI lead to profound alterations in the gut microbiota and their metabolic outputs, impacting not only the pathology of intestinal IRI itself but also influencing the function of other organs through various mechanisms. Notable among these are brain, liver, and kidney injuries, with acute lung injury being especially significant. This review seeks to explore in depth the roles and mechanisms of the gut microbiota and their metabolic products in the progression of acute lung injury initiated by intestinal IRI, aiming to provide a theoretical basis and directions for future research into the treatment of related conditions.
Assessment of genetic structure and trait associations of Watkins wheat landraces under Egyptian field conditions
Authors: Elkot Ahmed Fawzy , Nassar Ahmed E. , Elmassry Elsayed L. , Forner-Martínez Macarena , Awal Rajani , Wingen Luzie U. , Griffiths Simon , Alsamman Alsamman M. , Kehel Zakaria
Published: December 2024

Background

Wheat landraces represent a reservoir of genetic diversity that can support wheat improvement through breeding. A core panel of 300 Watkins wheat landraces, as well as 16 non-Watkins landraces and elite wheat cultivars, was grown during the 2020–2021 and 2021–2022 seasons at four Agricultural Research Stations in Egypt, Gemmiza, Nubaria, Sakha, and Sids, to evaluate the core panel for agromorphological and yield-related traits. The genetic population structure within these genotypes were assessed using 35,143 single nucleotide polymorphisms (SNPs).

Results

Cluster analyses using Discriminant Analysis of Principal Components (DAPC) and k-means revealed three clusters with moderate genetic differentiation and population structure, possibly due to wheat breeding systems and geographical isolation. The best ancestry was k = 4, but k = 2 and k = 3 were also significant. A genome-wide association study (GWAS) identified clustered marker trait associations (MTAs) linked to thousand kernel weight on chromosome 5A, plant height on chromosomes 3B and 1D, days to heading on chromosomes 2A, 4B, 5B and 1D, and plant maturity on chromosomes 3A, 2B, and 6B. In the future, these MTAs can be used to accelerate the incorporation of beneficial alleles into locally adapted germplasm through marker-assisted selection. Gene enrichment analysis identified key genes within these loci, including Reduced height-1 (Rht-A1) and stress-related genes.

Conclusion

These findings underscore significant genetic connections and the involvement of crucial biological pathways.
Fatty acid traits mediate the effects of uric acid on cancers: a Mendelian randomization study
Authors: Li Jianing , Zhang Yongsheng , Fu Tong , Wang Songyan , Cai Hongbo , Xu Fenghua , Xing Guoli , Tong Ying
Published: December 2024

Introduction

Previous findings on the association between uric acid (UA) levels and cancer risk are conflicting. Moreover, the mechanisms underlying the interactions between UA levels, fatty acid traits, and cancer outcomes remain complex; it is still unclear whether elevated UA levels influence fatty acid traits and, thereby, contribute to an increased cancer risk. Therefore, we aimed to investigate the association between UA levels and cancer risk, with a specific focus on the potential mediating role of fatty acid traits.

Methods

We employed a Mendelian randomization (MR) analysis utilizing genetic data from large-scale genome-wide association studies to assess the causal relationships among UA levels, fatty acid traits, and cancer risk. The primary method used was the inverse variance-weighted approach alongside Bayesian-weighted Mendelian randomization. Other MR models were also applied for comparison. Sensitivity analyses, based on various statistical assumptions, were also performed to evaluate the robustness of the findings. A two-step MR analysis was conducted to explore the mediating effects of fatty acid traits on the relationship between UA levels and cancer risk.

Results and Discussion

Elevated UA levels were associated with an increased risk of in situ neoplasms, cervical cancer, and invasive mucinous ovarian cancer, while they were linked to a decreased risk of cancers of the eye and adnexa, small cell lung cancer, bronchus and lung cancer, respiratory system and intrathoracic organ cancers, as well as lung cancer. Mediation analysis revealed that fatty acid traits, particularly the docosahexaenoic acid/trans fatty acid ratio, mediated the relationship between UA levels and lung cancer risk. These findings underscore the potential of fatty acid traits to mediate the association between UA levels and cancer risk, offering new insights for targeted interventions and potentially improving clinical outcomes.
Video tracking of single cells to identify clustering behavior
Authors: Korsnes Mónica Suárez , Ramberg Håkon André , Taskén Kristin Austlid , Korsnes Reinert
Published: December 2024

Cancer cell clustering is a critical factor in metastasis, with cells often believed to migrate in groups as they establish themselves in new environments. This study presents preliminary findings from an in vitro experiment, suggesting that co-culturing cells provides an effective method for observing this phenomenon, even though the cells are grown as monolayers. We introduce a novel single-cell tracking approach based on graph theory to identify clusters in PC3 cells cultivated in both monoculture and co-culture with PC12 cells, using 66-h time-lapse recordings. The initial step consists of defining “linked” pairs of PC3 cells, laying the foundation for the application of graph theory. We propose two alternative definitions for cell pairings. The first method, Method 1, defines cells as “linked” at a given time t if they are close together within a defined time period before and after t. A second potential alternative method, Method 2, pairs cells if there is an overlap between the convex hulls of their respective tracks during this time period. Pairing cells enables the application of graph theory for subsequent analysis. This framework represents a cell as a vertex (node) and a relation between two cells as an edge. An interconnected set of high-degree nodes (nodes with many connections or edges) forms a subgraph, or backbone, that defines a patch (cluster) of cells. All nodes connected to this backbone are part of the subgraph. The backbone of high-degree nodes functions as a partition (or cut) of the initial graph. Two consecutive clusters in the video are considered to share the same identity if the following cluster contains at least p = 75 % of the cells from the preceding cluster, and the mean positions of their cells are within △r = 75μm. PC3 cells grown in co-culture appear to form persistent clusters exceeding 10 cells after 40–50 h incubation following seeding. In contrast, PC3 cells cultured alone (mono-culture) did not exhibit this behavior. This approach is experimental and requires further validation with a broader dataset.
Quantification of PD-L1 expression and tumor mutational burden in biologically distinct advanced pancreatic cancers responding to pembrolizumab: case reports
Authors: Li Kevin Y. , Lowy Andrew M. , Fanta Paul
Published: December 2024

Background

The advent of checkpoint therapy is one of the most important recent advancements in cancer therapy. Though checkpoint therapy is a mainstay in some cancers, it has been largely ineffective in treating cancers of the pancreas. Pancreatic ductal adenocarcinoma and pancreatic neuroendocrine tumors are seldom responsive to checkpoint inhibition.

Case presentations

Here we present two cases of advanced pancreatic cancers that either failed to respond or recurred following conventional treatments. Tissue from each tumor was sequenced and analyzed for PD-L1 expression. Each patient was started on checkpoint blockade after assessing for a predictive biomarker, either the combined positive score or the tumor mutational burden. In each case, checkpoint blockade led to durable radiographic responses.

Conclusions

We therefore propose that it is reasonable to assess combined positive score and tumor mutational burden in refractory or recurrent pancreatic cancers when initiation of ICB is being considered.
Hyper-fractionated radiotherapy as a bridging strategy to enhance CAR-T efficacy by regulating T-cell co-stimulatory molecules in relapsed/refractory diffuse large B-cell lymphoma
Authors: Ruan Jing , Zhou Daobin , Zhang Yan , Zhao Danqing , Wei Chong , Hu Ke , Zhang Fuquan , Hou Xiaorong , Zhang Wei
Published: December 2024

Background

Bridging therapy can prevent patients from disease progression while waiting for CAR-T cell preparation. Hyper-fractionated radiotherapy can achieve an effective target dose within a short period, minimize radiation damage, and may modify immune environment compared to conventional radiotherapy.

Aims

This study aims to investigate the efficacy and safety of bridging hyper-fractionated radiotherapy in combination with CAR-T therapy for relapsed/refractory diffuse large B-cell lymphoma. The potential mechanisms were explored.

Methods

This is a prospective pilot study. After T-cell collection, the patients underwent hyper-fractionated radiotherapy at lesion sites with 1.5 Gy twice daily for 10 days before CAR-T cell infusion. Peripheral blood immune cell subsets and quantitative serum proteomics were assessed before radiotherapy and after radiotherapy before CAR-T cell infusion.

Results

A total of 13 patients have been enrolled. The median follow-up time was 6 (3–24) months after CAR-T infusion. At 3-month follow-up, 9/13(69%) patients had CR, 1/13(8%) patient had PR, 1/13(8%) patient remained SD, and 2/13(15%) patients died of disease progression. The local recurrence rate was 1/13(8%). Seven patients have been followed up for more than 6 months, and they remain in CR. The median PFS and OS were not reached. No grade 3–4 CRS or ICANS were reported. After hyper-fractionated radiotherapy, peripheral PD1+CD8+T/T ratio significantly decreased while quantitative serum proteomics profiling showed a decrease in sCD28.

Conclusion

Hyper-fractionated radiotherapy can rapidly control tumor progression sites without delaying the infusion time. This approach can improve the ORR and does not increase the incidence of CRS and ICANS. The mechanism may be related to the regulation of T-cell co-stimulatory molecules, which demands further exploration.
Validation of the clinical assessment scale for autoimmune encephalitis in a severe autoimmune encephalitis cohort
Authors: He Yu , Li Fangfang , Yang Ali , Yu Chen , Wang Yifan , Zhao Jing , Zang Weizhou
Published: December 2024

Objective

The Clinical Assessment Scale for Autoimmune Encephalitis (CASE) is a novel tool tailored specifically for evaluating the severity of autoimmune encephalitis (AE). However, its application in severe AE patients is limited. This study aimed to evaluate the reliability and validity of the CASE and explore its clinical significance in a severe AE cohort.

Methods

The relevant clinical characteristics, laboratory data, and prognosis of patients diagnosed with severe AE between April 2017 and April 2023 were collected. The CASE and modified Rankin scale (mRS) were performed at admission, discharge, and 1-year follow-up, respectively. The reliability of CASE was validated by calculating the Cronbach’s alpha value. The validity was evaluated by calculating the Spearman’s rank correlation with the corresponding mRS. Univariate and multivariate logistic regression were utilized to identify risk factors for poor prognosis.

Results

A total of 140 patients were recruited for the study. The CASE scale presented great internal consistency, with Cronbach’s α value of 0.768 for the total score. The Spearman’s rank correlation analysis revealed strong criterion validity between CASE and mRS, with coefficients of 0.68, 0.92, and 0.95 at admission, discharge, and 1-year follow-up, respectively (all p < 0.001). ROC analysis identified CASE score at admission served as a promising predictive marker for clinical response to treatment, with an AUC of 0.67 (95% CI: 0.57-0.77, p = 0.003). The optimal cut-off point was 22.5. At 1-year follow-up, 72/140 (51.4%) patients achieved good functional status (mRS, 0-2). Multivariate logistic regression confirmed that higher CASE scores on admission and older age at onset were associated with poor short-term as well as 1-year prognosis, respectively. In addition, no clinical response to treatment (OR = 40.499; 95% CI: 7.077-231.746, p < 0.001) and longer duration of hospitalization (OR = 1.071; 95% CI: 1.017-1.128, p = 0.010) were associated with poor function states at 1-year follow-up.

Conclusion

The CASE has proven suitable for evaluating disease severity and prognosis in severe AE patients. Besides, CASE score, age at disease onset, hospital stays, and response to immunotherapy are identified as independent risk factors for unsatisfactory prognosis in severe AE patients.
Harnessing m1A modification: a new frontier in cancer immunotherapy
Authors: Wang Xinru , Ma Xiaoqing , Chen Siyu , Fan Minyan , Jin Chenying , Chen Yushi , Wang Shaodong , Wang Zhiying , Meng Fei , Zhang Chengwan , Yang Lin
Published: December 2024

N1-methyladenosine (m1A) modification is an epigenetic change that occurs on RNA molecules, regulated by a suite of enzymes including methyltransferases (writers), demethylases (erasers), and m1A-recognizing proteins (readers). This modification significantly impacts the function of RNA and various biological processes by affecting the structure, stability, translation, metabolism, and gene expression of RNA. Thereby, m1A modification is closely associated with the occurrence and progression of cancer. This review aims to explore the role of m1A modification in tumor immunity. m1A affects tumor immune responses by directly regulating immune cells and indirectly modulating tumor microenvironment. Besides, we also discuss the implications of m1A-mediated metabolic reprogramming and its nexus with immune checkpoint inhibitors, unveiling promising avenues for immunotherapeutic intervention. Additionally, the m1AScore, established based on the expression patterns of m1A modification, can be used to predict tumor prognosis and guide personalized therapy. Our review underscores the significance of m1A modification as a burgeoning frontier in cancer biology and immuno-oncology, with the potential to revolutionize cancer treatment strategies.
Total Alkaloids of Rhizoma Corydalis regulates gut microbiota and restores gut immune barrier to ameliorate cognitive dysfunction in diabetic rats
Authors: Qi Yazhi , Li Jun , Tang Ya , Cao Rui , Gao Yishu , Xu Qiang , Han Yusheng
Published: December 2024

Background and objectives

Given the widespread dysbiosis of gut microbiota in patients with T2DM, it has been found that the microbiota-gut-brain axis plays an influential regulatory role in diabetic cognitive dysfunction, and improving gut dysbiosis may be a potential strategy for treating diabetic cognitive dysfunction. Total Alkaloids of Rhizoma Corydalis (TAC) is the main active component extracted from Rhizoma Corydalis. Pharmacological studies have demonstrated its significant pharmacological effects on the cardiovascular and cerebrovascular systems, and berberine, the main component of TAC, has a certain regulatory effect on gut microbiota.

Materials and methods

Rats were randomly divided into Control group, Model group, TAC-low group, TAC-mid group and TAC-high group. Cognitive function of diabetic rats was evaluated through behavioral testing using the Morris water maze experiment. The relative abundance of gut bacteria in rat feces was determined via 16S rRNA analysis. IHC and Western blot techniques were employed to assess IL-22, IL-23, Reg3g, ZO-1, occludin 1 expression in the colon tissue; GPX4, xCT, NLRP3, Caspase-1 p20, GSDMD-N were detected in the hippocampus.

Results

The cognitive function of diabetic rats decreased significantly. TAC demonstrated a significant reduction in inflammatory factors in serum, hippocampus, and colon, thus alleviating inflammation. Additionally, it effectively decreased ferroptosis induced by NLRP3 and reduced pathological damage in the hippocampus of diabetic rats. After treatment, the differential microbiota such as Lachnoclotridium and Bacteroides. TAC improved gut barrier permeability and integrity in rats while remodeling gut mucosal homeostasis. Moreover, pyroptosis and ferroptosis caused by the inflammatory cascade in the rat hippocampus were also significantly inhibited.

Conclusion

The combination of high lipid and high glucose with STZ can result in gut microbiota disturbance, damage gut immune barrier, decreased gut mucosal permeability and integrity, aggravated gut inflammation, further spread inflammatory factors to brain tissue, cause inflammatory cascade reaction of encephalopathy, and ultimately resulting in neuronal ferroptosis and cognitive dysfunction in diabetes mellitus. Our study suggests that TAC may regulate gut microbiota, restore gut immune homeostasis, improve gut barrier permeability and integrity, inhibit brain tissue inflammatory cascade, reduce neuronal ferroptosis, and thus improve diabetes. This provides new targets for its treatment strategy.
Gatifloxacin hydrochloride confers broad-spectrum antibacterial activity against phytopathogenic bacteria
Authors: Huang Yanxia , Peng Bin , Li Chenhui , Wu Yuqin , Zeng Zixian , Tariq Moh , Jiang Lin , Li Shun-xiang , Wu Dousheng
Published: December 2024

Bacterial diseases pose significant threats to agriculture and natural ecosystems, causing substantial crop losses and impacting food security. Until now, there has been a less efficient control strategy against some bacterial diseases such as bacterial wilt, caused by Ralstonia solanacearum. In this study, we screened a library of 58 microorganism-derived natural products for their antibacterial activity against R. solanacearum. Gatifloxacin hydrochloride exhibited the best inhibitory effect with an inhibition rate of 95% at 0.0625 mg/L. Further experiments demonstrate that gatifloxacin hydrochloride inhibits R. solanacearum growth in a concentration-dependent manner, with the minimum inhibitory concentration of 0.125 mg/L. Treatment with 0.5 mg/L of gatifloxacin hydrochloride killed more than 95% of bacteria. Gatifloxacin hydrochloride significantly inhibited biofilm formation by R. solanacearum. Gatifloxacin hydrochloride also shows good antibacterial activity against Pseudomonas syringae pv. tomato DC3000 and Xanthomonas campestris pv. vesicatoria. Exogenous application of gatifloxacin hydrochloride suppressed disease development caused by R. solanacearum and P. syringae. In summary, our results demonstrate the great potential of microorganism-derived compounds as broad-spectrum antibacterial compounds, providing alternative ways for the efficient control of bacterial plant diseases.
Mortality of chronic disorders of consciousness in adults and adolescents – a retrospective community based study from Salzburg, Austria
Authors: Schnetzer Laura , Prüwasser Tanja , Bergmann Jürgen , Zimmermann Georg , Kronbichler Martin , Leis Stefan , Trinka Eugen
Published: December 2024

Introduction

Epidemiological data on disorders of consciousness (DoC) is rare and very heterogeneous due to difficulties in case ascertainment and differences in health care pathways between countries. This study reports data on mortality and survival time for DoC patients in Salzburg, Austria.

Methods

All patients with DoC were registered in the health care region of Salzburg North, Austria between 2007 and 2022 and their death data retrieved from the Statistik Austria. The 1- and 5-year mortality was calculated, also in relation to several explanatory variables (age, sex, etiology, diagnosis, CRS-R score, improvement). Furthermore, the incidence, survival functions using the Kaplan–Meier estimator and a Cox-Regression were calculated.

Results

The mean annual incidence is 2.2 DoC/100.000 inhabitants in the Salzburg North region. The crude 1- and 5-year mortality rates were 25.9 and 55.1%, respectively, and the median survival of DoC patients based on the Kaplan–Meier estimator was 6.3 years. Moreover, the mortality was lower in women and in younger patients, those of traumatic etiology, and those with higher CRS-R scores, better diagnosis or an improvement of diagnosis until discharge from hospital.

Conclusion

This article gives a rare insight into epidemiological data on DoC and shows which factors influence the mortality of these patients. Moreover, it is the first community based study on mortality of DoC in Salzburg, Austria.
A real-world study: third-line treatment options for metastatic colorectal cancer
Authors: Wu Chen , Li Shuai , Hou Xinfang
Published: December 2024

Background

Numerous third-line treatment options exist for colorectal cancer. This study aims to assess the efficacy and safety of third-line therapies, including TKIs (fruquintinib, regorafenib) combined with PD-1 inhibitors, and trifluridine/tipiracil combined with bevacizumab, in patients with refractory microsatellite stable metastatic colorectal cancer who have progressed or are intolerant following standard first- and second-line treatments.

Materials and methods

This retrospective analysis collected data from patients with microsatellite stable advanced colorectal adenocarcinoma, diagnosed through histopathology and treated at Henan Provincial Cancer Hospital from May 2019 to April 2023. We compared the efficacy and safety of fruquintinib combined with PD-1 inhibitors, regorafenib combined with PD-1 inhibitors, and trifluridine/tipiracil combined with bevacizumab.

Results

Among 60 eligible patients with refractory microsatellite stable metastatic colorectal adenocarcinoma, 29 (48.3%) received fruquintinib combined with PD-1 inhibitors, 15 (25%) received regorafenib combined with PD-1 inhibitors, and 16 (26.7%) received trifluridine/tipiracil combined with bevacizumab. The average follow-up period was 12.6 months (ranging from 2.3 to 37.6 months). After third-line treatment, the overall objective response rate (ORR) was 8.6%, and the disease control rate (DCR) was 78.6%. The median overall survival (OS) for the regorafenib, fruquintinib, and trifluridine/tipiracil groups was 19.2 months, 14.0 months, and 16.2 months, respectively, with no statistically significant differences observed. However, there were statistically significant differences in progression-free survival (PFS); the median PFS for the regorafenib group was 6.3 months, for the fruquintinib group was 4.2 months, and for the trifluridine/tipiracil group was 5.4 months. Pairwise comparisons indicated that the PFS for the regorafenib group was similar to that for the trifluridine/tipiracil group, both of which were superior to the fruquintinib group. Cox univariate regression analysis revealed that the presence of liver and peritoneal metastases was associated with PFS in third-line treatment.

Conclusion

In the third-line treatment of colorectal cancer, regorafenib combined with PD-1 inhibitors and trifluridine/tipiracil combined with bevacizumab showed superiority over fruquintinib combined with PD-1 inhibitors in terms of PFS, but no statistically significant difference in OS was noted among the three groups.
The use of alpha-adrenergic antagonists in pediatric nephrolithiasis: a systematic review
Authors: Haddad Firas , Farhat Walid A. , Cannon Shannon
Published: December 2024

Objective

To evaluate existing clinical evidence for the efficacy of alpha blockers in the management of pediatric stone disease.

Methods

We conducted a systematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Cohort and randomized control trials of patients less than 18 years old with kidney stones managed with alpha-adrenergic antagonists were included. Outcomes included stone expulsion time, stone passage rate, mean number of pain episodes, and mean need for analgesics. We performed data extraction of the selected articles, and results were assimilated and synthesized qualitatively. Data extraction and risk of bias assessment was conducted by two independent reviewers.

Results

Of 257 relevant studies, 9 studies with 1,039 patients were included. Six studies measured stone expulsion time, with 5 studies noting statistically significant decreases in stone expulsion time for the treatment group compared to the control. Seven studies measured the stone expulsion rate, and 5 reported a statistically significant increased expulsion rate in the treatment group. Four studies reported a decrease in the mean number of pain episodes in the treatment group and two studies showed a decreased analgesic requirement compared to control. Two studies found alpha blockers not superior to watchful waiting after shock wave lithotripsy. Risk of bias was high in some studies, primarily due to incomplete reporting on methodology and study design.

Conclusions

Alpha blockers are supported by a growing body of evidence to be effective against nephrolithiasis in children, however large-scale, well-designed studies are needed to confirm these findings.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=330068, PROSPERO (CRD42022330068).
Literature review of the clinical features of sulfasalazine-induced drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome (DRESS/DIHS)
Authors: Liu Ya , Wang Danxia , Wu Shiwei , Liu Xiang , Xiao Can
Published: December 2024

Background

Sulfasalazine (SSZ) is commonly prescribed for the treatment of ulcerative colitis, rheumatoid arthritis, and ankylosing spondylitis. However, it can also trigger a severe drug reaction known as Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) or Drug-Induced Hypersensitivity Syndrome (DIHS). This article aims to analyze the clinical characteristics of DRESS/DIHS induced by SSZ and provide evidence for clinical diagnosis, treatment, and prevention.

Methods

We gathered relevant literature on SSZ-induced DRESS/DIHS published from 1 January 2005, to 21 July 2024, by searching both English and Chinese databases.

Results

Thirty-nine patients (15 males and 24 females) were included in the study, with a median age of 47 years (range: 11–82 years). Following SSZ administration, the median onset time of DRESS/DIHS was 28 days (range: 10–60 days). These patients exhibited clinical symptoms such as fever (100%), rash (100%), digestive system responses (38.5%), and edema (35.9%). Organ involvement was observed in 38 patients, with commonly affected organs being lymph nodes (78.9%), liver (94.7%), kidney (15.8%), heart (13.2%), and lung (7.9%). All patients had hematological abnormalities, primarily eosinophilia (69.2%) and atypical lymphocytosis (35.9%). Additional hematological changes included agranulocytosis (5.1%), hemophagocytic syndrome (5.1%), and pancytopenia (2.6%). Virus reactivation occurred in 21 patients (53.8%). The primary treatment for DRESS/DIHS due to SSZ is the immediate cessation of the drug, followed by systemic corticosteroid administration. Alternative treatments such as cyclosporine, intravenous immunoglobulin (IVIG), mycophenolate mofetil, cyclophosphamide, and rituximab require further investigation to establish their efficacy.

Conclusion

SSZ may lead to DRESS/DIHS. To make a conclusive diagnosis, healthcare providers should conduct a thorough assessment by examining the patient’s clinical presentation, conducting physical evaluations, and analyzing laboratory findings. Immediate discontinuation of SSZ is recommended, and corticosteroids are often considered an efficacious treatment for DRESS/DIHS.
Efficacy of Oroxylin A in ameliorating renal fibrosis with emphasis on Sirt1 activation and TGF-β/Smad3 pathway modulation
Authors: Li Guangzhuang , Xian Sentao , Cheng Xianchao , Hou Yunhua , Jia Wenqing , Ma Yukui
Published: December 2024

Introduction

Renal fibrosis poses a serious threat to human health. At present, there are few types of traditional Chinese medicine used to treat this disease, and Oroxylin A (OA), as a natural product with multiple biological activities, is expected to be used for the treatment of renal fibrosis.

Methods

The tolerance of osteoarthritis and its impact on renal fibrosis were studied through ADMET, Lipinski’s filter, establishment of a unilateral ureteral obstruction (UUO) model, and molecular docking.

Results

OA has good drug tolerance. Compared with the sham group, UUO mice that did not receive OA treatment showed severe tubular dilation and atrophy, extracellular matrix (ECM) deposition, and inflammatory cell infiltration in their kidneys, while OA-treated mice showed significant improvement in these symptoms. OA treatment remarkably restrained the accumulation of fibronectin and α-SMA. Moreover, OA treatment remarkably decreased the abnormal upregulation of inflammatory factors (IL-1β, IL-6, and TNF-α) in the obstructed kidney of UUO mice. Sirtuin1 (Sirt1) expression was markedly diminished in the kidneys of UUO mice and TGF-β1-induced HK-2 cells, whereas this reduction was largely reversed after OA treatment. The results support that OA exerts antifibrotic effects partly through the promotion of the activity of Sirt1. In in vitro results, OA treatment markedly inhibited the activation of Smad3 in UUO mice, thereby ameliorating renal fibrosis. OA could form hydrogen bonds with key the amino acid ASN226 in Sirt1, thereby activating Sirt1, which might also be the reason why OA could resist renal fibrosis.

Discussion

Our study indicated that OA might exert anti-renal fibrosis effects through the activation of Sirt1 and the suppression of the TGF-β/Smad3 signaling pathway.
Efficacy and safety of oral propranolol and topical timolol in the treatment of infantile hemangioma: a meta-analysis and systematic review
Authors: Huang Xiaoye , Si Wenyue , Zou Zhili , Li Binyao , Mu Yide , Zhong Wei , Yang Kaiying
Published: December 2024

Background

Propranolol, a nonselective β-blocker, is the first-line treatment for infantile hemangioma (IH). Topical timolol has recently been proposed as a novel IH treatment with fewer adverse effects. This study was conducted to compare the efficacy and safety of oral propranolol and topical timolol for treating IH.

Methods

Studies were included after searching PubMed, Embase, Web of Science, and the Cochrane Library via the keywords of “propranolol”, “timolol”, “infantile hemangioma” and their synonyms. A meta-analysis with pooled odds ratios was performed using the fixed-effect model.

Results

Seven articles with 2071 patients were included in this meta-analysis. Compared with topical timolol, oral propranolol had a greater response rate (OR = 2.12, P < 0.001), but it was also associated with a greater risk of adverse events (OR = 2.31, P < 0.001). For superficial IH, timolol demonstrated similar efficacy to propranolol (OR = 1.28, P = 0.34) but with fewer adverse events (OR = 2.30, P = 0.001). Additionally, compared with topical timolol, propranolol at a dosage of 2 mg/kg/d had a better response rate (OR = 2.62, P < 0.001), whereas the 1.0∼1.5 mg/kg/d propranolol group showed no significant difference (OR = 1.34, P = 0.38).

Conclusion

Oral propranolol presents superior therapeutic efficacy in the treatment of IH compared to topical timolol. However, topical timolol can serve as an alternative to oral propranolol for treating superficial IH, providing similar efficacy with fewer adverse effects. Additionally, propranolol at a dosage of 2 mg/kg/d offers greater efficacy with a comparable safety profile, whereas the 1.0∼1.5 mg/kg/d propranolol dosage shows no significant difference in efficacy compared to timolol but is associated with more adverse events.

Systematic Review Registration

https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42024603724, identifier CRD42024603724.
The use of microbial rhodopsin proteins in differential photodetection
Authors: Reissig Louisa , Buchanan Kirstin , Lindner Thea , Kurihara Marie , Chan Po-Chuan , Kibowski Falk , Kojima Keiichi , Dalgleish Simon , Awaga Kunio , Sudo Yuki
Published: December 2024

Transferring information using light signals, and detecting these signals, is not only a cornerstone of modern technology, but has been essential for organisms since evolution provided them with proteins - the cell’s custom-built tools - capable of light to energy conversion or photo-sensing. In this study, the use of diverse representatives of the photoactive protein family of microbial rhodopsins as the active material in differential photodetector devices has been investigated. By modifying the internal parameters of the detectors, such as rhodopsin kind, salinity and pH, as well as by tuning the external environment, such as temperature, we could increase the responsivity and speed of our devices by over 2 orders of magnitude, compared to a previously reported proof-of-concept device, to the µA/W and kHz range, respectively. The characteristic differential photodetector transient signal shape could be stably observed for temperatures up to 70°C and related to features in the protein’s cyclic reaction upon light activation, with the changes in photocurrent shape and polarity concomitantly providing information about the protein used in the device. Furthermore, this study demonstrates that the use of proteins - the cell’s molecular machines - instead of simple organic semiconductor materials can add secondary sensor functionalities to the device if the stimulus (here through temperature and pH) has sufficient effect on the photocurrent signal to allow calibration.
A comparative study of the quality differences and seasonal dynamics of flavonoids between the aerial parts and roots of Scutellaria barbata
Authors: Cheng Yijie , Cao Wenxin , Guo Ru , Chen Ruihuan , Li Xiaofan , Qian Da , Xu Jingyuan
Published: December 2024

Introduction

Scutellaria barbata D. Don is a widely cultivated Chinese herbal medicine known for its medicinal properties. However, differences in the spatial distribution of metabolites, accumulation patterns of flavonoids, and pharmacological activities between the aerial parts and roots of S. barbata still remain unclear, posing challenges for its standardized cultivation and quality control. This study aimed to elucidate the quality differences between these plant parts and clarify their seasonal variations.

Methods

The chemical profiles were qualitatively analyzed by UPLC-QTOF-MS/MS. The accumulation patterns of total flavonoids, scutellarin and baicalin in different parts of S. barbata were quantitatively analyzed by UV and HPLC respectively. The differences of pharmacological efficacy were evaluated by antioxidant assays and CCK-8 assay.

Results

In this research, there were 46 compounds identified in S. barbata that included 44 flavonoids. The aerial parts primarily accumulate flavonoids with 4′-hydroxyl group, while the root mainly accumulate flavonoids without this group. Additionally, the accumulation and variation of flavonoid components were seasonally dependent, with the aerial parts reaching peak content in spring during vigorous vegetative growth and the roots accumulating most flavonoids in autumn. The extracts from both parts exhibited antioxidant activity and inhibitory effects on cancer cell proliferation, with notable differences between them.

Discussion

This study provides valuable insights into the quality differences and seasonal dynamics of the different parts of S. barbata, offering a reference for standardized harvesting and quality control.