bluuebunny/crossref_metadata_2025_split huggingface dataset:
External validation of a novel nomogram for diagnosis of Protein Energy Wasting in adult hemodialysis patients
Authors: Yan Danying , Wang Yi , Hu Jing , Lu Renhua , Ye Chaoyang , Liu Nanmei , Chen Dongping , Liang Weiwei , Zheng Liang , Liu Wenrui , Lan Tianying , Lan Naiying , Shao Qing , Zhuang Shougang , Ma Xiaoyan , Liu Na 
Published: August 2024

BackgroundProtein Energy Wasting (PEW) has high incidence in adult hemodialysis patients and refers to a state of decreased protein and energy substance. It has been demonstrated that PEW highly affects the quality of survival and increases the risk of death. Nevertheless, its diagnostic criteria are complex in clinic. To simplify the diagnosis method of PEW in adult hemodialysis patients, we previously established a novel clinical prediction model that was well-validated internally using bootstrapping. In this multicenter cross-sectional study, we aimed to externally validate this nomogram in a new cohort of adult hemodialysis patients.MethodsThe novel prediction model was built by combining four independent variables with part of the International Society of Renal Nutrition and Metabolism (ISRNM) diagnostic criteria including albumin, total cholesterol, and body mass index (BMI). We evaluated the performance of the new model using discrimination (Concordance Index), calibration plots, and Clinical Impact Curve to assess its predictive utility.ResultsFrom September 1st, 2022 to August 31st, 2023, 1,158 patients were screened in five medical centers in Shanghai. 622 (53.7%) hemodialysis patients were included for analysis. The PEW predictive model was acceptable discrimination with the area under the curve of 0.777 (95% CI 0.741–0.814). Additionally, the model revealed well-fitted calibration curves. The McNemar test showed the novel model had similar diagnostic efficacy with the gold standard diagnostic method (p &gt; 0.05).ConclusionOur results from this cross-sectional external validation study further demonstrate that the novel model is a valid tool to identify PEW in adult hemodialysis patients effectively.
Development of an algorithm to identify small cell lung cancer patients in claims databases
Authors: Danese Mark D. , Balasubramanian Akhila , Bebb D. Gwyn , Pundole Xerxes 
Published: August 2024

IntroductionThe treatment landscape of small cell lung cancer (SCLC) is evolving. Evidence generated from administrative claims is needed to characterize real-world SCLC patients. However, the current ICD-10 coding system cannot distinguish SCLC from non-small cell lung cancer (NSCLC). We developed and estimated the accuracy of an algorithm to identify SCLC in claims-only databases.MethodsWe performed a cross-sectional study of lung cancer patients diagnosed from 2016-2017 using the Surveillance, Epidemiology and End Results (SEER), linked with Medicare database. The analysis included two phases – data exploration (utilizing a 25% random sample) and data validation (remaining 75% sample). The SEER definition of SCLC and NSCLC were used as the gold standard. Claims-based algorithms were identified and evaluated for their sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV).ResultsThe eligible cohort included 31,912 lung cancer patients. The mean age was 76.3 years, 44.6% were male, with 9.4% having SCLC and 90.6% identified as NSCLC using SEER. The exploration analysis identified potential algorithms based on treatment data. In the validation analysis of 7,438 lung cancer patients who received systemic treatment in the outpatient setting, an etoposide-based algorithm (etoposide use in 180 days following lung cancer diagnosis) to identify SCLC showed: sensitivity 95%, specificity 95%, PPV 82% and NPV 99%.DiscussionAn etoposide treatment-based algorithm showed good accuracy in identifying SCLC patients. Such algorithms can facilitate analyses of treatment patterns, outcomes, healthcare resource and costs among treated SCLC patients, thereby bolstering the evidence-base for best patient care.
Association of the rs1042522 SNP with prostate cancer risk: a study of cancer tissues, primary tumor cultures, and serum samples from a Spanish Caucasian population
Authors: Toscano-Guerra Emily , Maggio Valentina , García Javier , Semidey Maria Eugenia , Celma Ana , Morote Juan , de Torres Inés , Giralt Marina , Ferrer-Costa Roser , Paciucci Rosanna 
Published: August 2024

BackgroundProstate cancer (PCa) is a leading cause of cancer-related deaths in European men, emphasizing the urgent need for effective risk assessment strategies. The TP53 gene, a tumor suppressor gene frequently mutated in cancer, commonly harbors the rs1042522 single nucleotide polymorphism (SNP), known as the P72R SNP, which may influence PCa susceptibility. This study investigated the prevalence of the P72R SNP in European Caucasian PCa samples and its association with PCa risk.MethodsGenotyping was conducted on 12 hormone-naïve aggressive PCa cultures (hnPCs) from untreated patients (Gleason ≥8), 11 radical prostatectomies (RP), and 94 serum samples using DNA Sanger sequencing and melting curve analysis. Comparative analysis utilized data from the GnomAD database’s European Caucasian non-cancer population.ResultsOur results demonstrate a significantly higher frequency of the P72R SNP in PCa samples and serums compared to the general European non-cancer population. A robust and statistically significant association (p &lt; 0.0001) between the SNP and prostate cancer risk was identified, with an odds ratio of 7.937 (95% CI 5.37-11.00). Notably, the G allele (R72) showed a pronounced prevalence in high Gleason score (≥8) patients, although statistical significance was not reached. These results highlight a potential association with undifferentiated and malignant PCa lesions.ConclusionThe compelling association between the P72R SNP and prostate cancer risk underscores the potential utility of this marker for the early identification of patients at risk of aggressive metastatic prostate cancer. This insight could empower further research to intervene at an early stage by offering enhanced opportunities for timely and targeted interventions.
Primary intestinal diffuse large B-cell lymphoma: novel insights and clinical perception
Authors: Chen Xiaojun , Wang Jing , Liu Yanquan , Lin Suxia , Shen Jianzhen , Yin Yue , Wang Yili 
Published: August 2024

BackgroundExtranodal Non-Hodgkin lymphoma (NHL) is more prevalent in the gastrointestinal (GI) tract than in other sites. This study aimed to explore the clinical features and prognostic factors of primary intestinal diffuse large B-cell lymphoma (PI-DLBCL), in order to provide new references for basic research and clinical diagnosis and treatment of the rare extranodal malignant lymphoma.MethodsThe clinical data of 88 patients with PI-DLBCL admitted to Fujian Medical University Union Hospital from June 2011 to June 2022 were retrospectively studied, the clinical and pathological features, diagnosis and treatment process and prognosis of PI-DLBCL were analyzed, and univariate and multivariate analysis of prognostic factors was carried out. The Kaplan-Meier method was used for survival analysis. Meanwhile, the latest literature from PubMed was retrieved to systematically discuss the research progress in the diagnosis and treatment of PI-DLBCL.ResultsAmong the 88 patients with PI-DLBCL included in this study, 60 cases were males (68.18%), 28 cases were females (31.82%), and 62 patients (70.45%) were complaining of abdominal pain, and the second most common clinical manifestation was changes in bowel habits in 16 (18.18%), with a median age of onset of 57 (17–82) years. The first-line treatment regimen was surgery combined with R-CHOP chemotherapy (56.82%). The median follow-up time was 72 (1–148) months, 51 (57.95%) of 88 patients with PI-DLBCL survived, 30 patients (34.09%) died, 7 patients (7.95%) were lost to follow-up, and the PFS rates of 1-year, 3-year and 5-year were 57.95%, 29.55% and 15.91%, and the OS rates of 1-year, 3-year and 5-year were 79.55%, 45.45% and 28.41%, respectively. The results of univariate Cox regression analysis showed that ECOG score, Lugano stage, B symptoms, IPI score, white blood cells, serum LDH, albumin, β2 microglobulin were the influencing factors of OS in PI-DLBCL patients, and ECOG score, Lugano stage, B symptoms, IPI score, white blood cells, serum LDH, albumin, β2 microglobulin were all the influencing factors of PFS in PI-DLBCL patients. The results of multivariate Cox analysis showed that Lugano stage may be an independent prognostic factor affecting OS and PFS in PI-DLBCL patients.ConclusionPI-DLBCL is more common in middle-aged and elderly men, clinical manifestations lack specificity, first-line treatment is mainly surgery combined with standard chemotherapy regimens. The Lugano stage may be an independent prognostic factor affecting OS and PFS in PI-DLBCL patients.
Suppression of NLRP3 inflammasome orchestrates the protective efficacy of tiron against isoprenaline-induced myocardial injury
Authors: Abdelrahaman Doaa , Habotta Ola A. , Taher Ehab S. , El-Ashry Eman S. , Ibrahim Iman , Abdeen Ahmed , Ibrahim Ateya M. , Ibrahim Reham M. , Anwer Hala , Mihaela Ostan , Olga Rada , Alwutayed Khairiah M. , Al-Serwi Rasha H. , El-Sherbiny Mohamed , Sorour Safwa M. , El-Kashef Dalia H. 
Published: August 2024

The major contribution of myocardial damage to global mortalities raises debate regarding the exploration of new therapeutic strategies for its treatment. Therefore, our study investigated the counteracting effect of tiron against isoprenaline (ISO)-mediated cardiac infarction in mice. Tiron was administered to mice for 7 days prior to two consecutive injections of ISO on days 8 and 9 of the treatment protocol. Tiron significantly reduced the levels of CK-MB, LDH, and AST in serum samples of ISO-challenged mice. A considerable increase in the cardiac antioxidant response was observed in tiron-treated mice, as indicated by depletion of MDA and enhancement of antioxidant activities. Furthermore, tiron induced a marked decrease in NLRP3, ASC, and caspase-1 levels accompanied by weak immune reactions of IL-1β, NF-κB, TLR4, and iNOS in the infarct cardiac tissues. Histopathological screening validated these variations observed in the cardiac specimens. Thus, tiron clearly mitigated the oxidative and inflammatory stress by repressing the NLRP3 inflammasome and the TLR4/NF-κB/iNOS signaling cascade.
Puerarin attenuates myocardial ischemic injury and endoplasmic reticulum stress by upregulating the Mzb1 signal pathway
Authors: Xue Jiaojiao , Ren Haolin , Zhang Qi , Gu Jing , Xu Qian , Sun Jiaxi , Zhang Lu , Zhou Ming-Sheng 
Published: August 2024

ObjectiveThis study investigated the role of Mzb1 in puerarin protection against heart injury and dysfunction in acute myocardial infarction (AMI) mice.MethodsC57BL/6 mice were pretreated with and without puerarin at doses of 50 mg/kg and 100 mg/kg for 14 days before establishing the AMI model. An AMI model was induced by ligating the left descending anterior coronary artery, and AC16 cardiomyocytes were treated with H2O2in vitro. Echocardiography was performed to measure cardiac function. DHE staining, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase assay, and DCFH-DA oxidative fluorescence staining were used to determine reactive oxygen species (ROS) production in vivo and in vitro. Bioinformatics analysis was used to predict potential upstream transcription factors of Mzb1.ResultsPuerarin dose-dependently reduced myocardial infarction area and injury, accompanied by the improvement of cardiac function in AMI mice. AMI mice manifested an increase in myocardial oxidative stress, endoplasmic reticulum (ER) stress, apoptosis, and mitochondrial biogenesis dysfunction, which were inhibited by pretreatment with puerarin. Puerarin also prevented Mzb1 downregulation in the hearts of AMI mice or H2O2-treated AC16 cells. Consistent with the in vivo findings, puerarin inhibited H2O2-induced cardiomyocyte apoptosis, ER stress, and mitochondrial dysfunction, which were attenuated by siRNA Mzb1. Furthermore, the JASPAR website predicted that KLF4 may be a transcription factor for Mzb1. The expression of KLF4 was partially reversed by puerarin in the cardiomyocyte injury model, and KLF4 inhibitor (kenpaullone) inhibited Mzb1 expression and affected its function.ConclusionThese results suggest that puerarin can protect against cardiac injury by attenuating oxidative stress and endoplasmic reticulum stress through upregulating the KLF4/Mzb1 pathway and that puerarin may expand our armamentarium for the prevention and treatment of ischemic heart diseases.
Metformin-mediated effects on mesenchymal stem cells and mechanisms: proliferation, differentiation and aging
Authors: Liu Xinjuan , Li Zekun , Liu Luyun , Zhang Ping , Wang Yue , Ding Gang 
Published: August 2024

Mesenchymal stem cells (MSCs) are a type of pluripotent adult stem cell with strong self-renewal and multi-differentiation abilities. Their excellent biological traits, minimal immunogenicity, and abundant availability have made them the perfect seed cells for treating a wide range of diseases. After more than 60 years of clinical practice, metformin is currently one of the most commonly used hypoglycaemic drugs for type 2 diabetes in clinical practice. In addition, metformin has shown great potential in the treatment of various systemic diseases except for type 2 diabetes in recent years, and the mechanisms are involved with antioxidant stress, anti-inflammatory, and induced autophagy, etc. This article reviews the effects and the underlying mechanisms of metformin on the biological properties, including proliferation, multi-differentiation, and aging, of MSCs in vitro and in vivo with the aim of providing theoretical support for in-depth scientific research and clinical applications in MSCs-mediated disease treatment.
Metabolite profiling of chickpea (Cicer arietinum) in response to necrotrophic fungus Ascochyta rabiei
Authors: Raman Rosy , Morris Stephen , Sharma Niharika , Hobson Kristy , Moore Kevin 
Published: August 2024

IntroductionAscochyta blight (AB) caused by the necrotrophic fungus Ascochyta rabiei is one of the most significant diseases that limit the production of chickpea. Understanding the metabolic mechanisms underlying chickpea-A.rabiei interactions will provide important clues to develop novel approaches to manage this disease.MethodsWe performed metabolite profiling of the aerial tissue (leaf and stem) of two chickpea accessions comprising a moderately resistant breeding line (CICA1841) and a highly susceptible cultivar (Kyabra) in response to one of the highly aggressive Australian A. rabiei isolates TR9571 via non-targeted metabolomics analysis using liquid chromatography-mass spectrometry.ResultsThe results revealed resistance and susceptibility-associated constitutive metabolites for example the moderately resistant breeding line had a higher mass abundance of ferulic acid while the levels of catechins, phthalic acid, and nicotinic acid were high in the susceptible cultivar. Further, the host-pathogen interaction resulted in the altered levels of various metabolites (induced and suppressed), especially in the susceptible cultivar revealing a possible reason for susceptibility against A.r abiei. Noticeably, the mass abundance of salicylic acid was induced in the aerial tissue of the susceptible cultivar after fungus colonization, while methyl jasmonate (MeJA) was suppressed, elucidating the key role of phytohormones in chickpea-A. rabiei interaction. Many differential metabolites in flavonoid biosynthesis, phenylalanine, Aminoacyl-tRNA biosynthesis, pentose and glucuronate interconversions, arginine biosynthesis, valine, leucine, and isoleucine biosynthesis, and alanine, aspartate, and glutamate metabolism pathways were up- and down-regulated showing the involvement of these metabolic pathways in chickpea-A. rabiei interaction.DiscussionTaken together, this study highlights the chickpea − A. rabiei interaction at a metabolite level and shows how A. rabiei differentially alters the metabolite profile of moderately resistant and susceptible chickpea accessions and is probably exploiting the chickpea defense pathways in its favour.
Unlocking the puzzle: non-defining mutations in SARS-CoV-2 proteome may affect vaccine effectiveness
Authors: Ulzurrun Eugenia , Grande-Pérez Ana , del Hoyo Daniel , Guevara Cesar , Gil Carmen , Sorzano Carlos Oscar , Campillo Nuria E. 
Published: August 2024

IntroductionSARS-CoV-2 variants are defined by specific genome-wide mutations compared to the Wuhan genome. However, non-clade-defining mutations may also impact protein structure and function, potentially leading to reduced vaccine effectiveness. Our objective is to identify mutations across the entire viral genome rather than focus on individual mutations that may be associated with vaccine failure and to examine the physicochemical properties of the resulting amino acid changes.Materials and methodsWhole-genome consensus sequences of SARS-CoV-2 from COVID-19 patients were retrieved from the GISAID database. Analysis focused on Dataset_1 (7,154 genomes from Italy) and Dataset_2 (8,819 sequences from Spain). Bioinformatic tools identified amino acid changes resulting from codon mutations with frequencies of 10% or higher, and sequences were organized into sets based on identical amino acid combinations.ResultsNon-defining mutations in SARS-CoV-2 genomes belonging to clades 21 L (Omicron), 22B/22E (Omicron), 22F/23A (Omicron) and 21J (Delta) were associated with vaccine failure. Four sets of sequences from Dataset_1 were significantly linked to low vaccine coverage: one from clade 21L with mutations L3201F (ORF1a), A27- (S) and G30- (N); two sets shared by clades 22B and 22E with changes A27- (S), I68- (S), R346T (S) and G30- (N); and one set shared by clades 22F and 23A containing changes A27- (S), F486P (S) and G30- (N). Booster doses showed a slight improvement in protection against Omicron clades. Regarding 21J (Delta) two sets of sequences from Dataset_2 exhibited the combination of non-clade mutations P2046L (ORF1a), P2287S (ORF1a), L829I (ORF1b), T95I (S), Y145H (S), R158- (S) and Q9L (N), that was associated with vaccine failure.DiscussionVaccine coverage associations appear to be influenced by the mutations harbored by marketed vaccines. An analysis of the physicochemical properties of amino acid revealed that primarily hydrophobic and polar amino acid substitutions occurred. Our results suggest that non-defining mutations across the proteome of SARS-CoV-2 variants could affect the extent of protection of the COVID-19 vaccine. In addition, alteration of the physicochemical characteristics of viral amino acids could potentially disrupt protein structure or function or both.
Association analyses between urinary concentrations of multiple trace elements and gastric precancerous lesions and gastric cancer in Anhui province, eastern China
Authors: Qian Shiqing , Xu Fang , Wang Min , Zhang Meng , Ding Shaopeng , Jin Guoqing , Zhang Xiaohui , Cheng Wenli , Wang Li , Zhu Yuting , Wang Wuqi , Ofosuhemaa Princess , Wang Tingting , Lin Xiao , Zhu Yu , Lv Yaning , Hu Anla , Yang Wanshui , He Gengsheng , Zhao Qihong 
Published: August 2024

BackgroundLimited epidemiological evidence suggests that exposure to trace elements adversely impacts the development of gastric precancerous lesions (GPL) and gastric cancer (GC). This study aimed to estimate the association of individual urinary exposure to multiple elements with GPL and GC.MethodsA case-control investigation was conducted in Anhui Province from March 2021 to December 2022. A total of 528 subjects (randomly sampled from 1,020 patients with GPL, 200 patients with GC, and 762 normal controls) were included in our study. Urinary levels of iron (Fe), copper (Cu), zinc (Zn), nickel (Ni), strontium (Sr), and Cesium (Cs) were measured using inductively coupled plasma mass spectrometry (ICP-MS). Four different statistical approaches were employed to explore the risk of GPL and GC with mixed exposure, including multivariate logistic regression, weighted quantile regression (WQS), quantile g-computation (Qgcomp), and the Bayesian kernel machine regression (BKMR) model.ResultsThe WQS model indicated that urinary exposure to a mixture of elements is positively correlated with both GPL and GC, with ORs for the mixture exposure of 1.34 (95% CI: 1.34-1.61) for GPL and 1.38 (95% CI: 1.27-1.50) for GC. The Qgcomp and BKMR models also demonstrated a statistically significant positive correlation between the mixture and both GPL and GC.ConclusionConsidering the limitations of case-control studies, future prospective studies are warranted to elucidate the combined effects and mechanisms of trace elements exposure on human health.
Innovation: ice cream in the recovery room rules out chylothorax after thoracic lymphadenectomy and affords same-day chest tube removal
Authors: Cerfolio Robert J. , McCormack Ashley J. 
Published: August 2024

ObjectivesEarly removal of chest tubes reduces pain and morbidity. This study aimed to remove chest tubes immediately after robotic pulmonary resection with complete thoracic lymphadenectomy by administering ice cream to rule out chylothorax.MethodsThis quality improvement study utilized prospectively gathered data from one thoracic surgeon. Patients were given 3.6 fl oz of ice cream in the recovery room within 1 h after their operation. Chest tubes were removed within 4 h if there was no chylous drainage and air leak on the digital drainage system.ResultsFrom January 2022 to August 2023, 343 patients underwent robotic pulmonary resection with complete thoracic lymphadenectomy. The median time to ingest the ice cream was 1.5 h after skin closure. The incidence of chylothorax was 0.87% (3/343). Two patients were diagnosed with chylothorax after consuming ice cream within 4 h of surgery. One patient, whose chest tube remained in place due to an air leak, had a chylothorax diagnosed on postoperative day 1 (POD1). All three patients were discharged home on POD1 with their chest tubes in place, adhering to a no-fat, medium-chain triglyceride diet. All chylothoraces resolved within 6 days. None of the remaining patients developed chylothorax postoperatively with a minimum follow-up period of 90 days.ConclusionsProviding ice cream to patients after pulmonary resection and complete thoracic lymphadenectomy is an effective and reliable technique to rule out chylothorax early in the postoperative period and facilitates early chest tube removal. Further studies are needed to ensure that this simple, inexpensive test is reproducible.