bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

BackgroundWheat 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).ResultsCluster 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.ConclusionThese 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

IntroductionPrevious 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.MethodsWe 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.
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

BackgroundThe 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 presentationsHere 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.ConclusionsWe 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

BackgroundBridging 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.AimsThis 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.MethodsThis 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.ResultsA 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.ConclusionHyper-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

ObjectiveThe 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.MethodsThe 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.ResultsA 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 &lt; 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 &lt; 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.ConclusionThe 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.
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 objectivesGiven 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 methodsRats 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.ResultsThe 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.ConclusionThe 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.
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

IntroductionEpidemiological 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.MethodsAll 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.ResultsThe 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.ConclusionThis 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

BackgroundNumerous 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 methodsThis 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.ResultsAmong 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.ConclusionIn 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

ObjectiveTo evaluate existing clinical evidence for the efficacy of alpha blockers in the management of pediatric stone disease.MethodsWe 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.ResultsOf 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.ConclusionsAlpha 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 Registrationhttps://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

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

IntroductionRenal 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.MethodsThe 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.ResultsOA 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.DiscussionOur 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.