bluuebunny/crossref_metadata_2025_split huggingface dataset:
PLP1 may serve as a potential diagnostic biomarker of uterine fibroids
Authors: Cai Lei , Liao Zhiqi , Li Shiyu , Wu Ruxing , Li Jie , Ren Fang , Zhang Hanwang 
Published: October 2022

Objective: We aim to identify the crucial genes or potential biomarkers associated with uterine fibroids (UFs), which may provide clinicians with evidence about the diagnostic biomarker of UFs and reveal the mechanism of its progression.Methods: The gene expression and genome-wide DNA methylation profiles were obtained from Gene Expression Omnibus database (GEO). GSE45189, GSE31699, and GSE593 datasets were included. GEO2R and Venn diagrams were used to analyze the differentially expressed genes (DEGs) and extract the hub genes. Gene Ontology (GO) analysis was performed by the online tool Database for Annotation, Visualization, and Integrated Discovery (DAVID). The mRNA and protein expression of hub genes were validated by RT-qPCR, western blot, and immunohistochemistry. The receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value.Results: We detected 22 DEGs between UFs and normal myometrium, which were enriched in cell maturation, apoptotic process, hypoxia, protein binding, and cytoplasm for cell composition. By finding the intersection of the data between differentially expressed mRNA and DNA methylation profiles, 3 hub genes were identified, including transmembrane 4 L six family member 1 (TM4SF1), TNF superfamily member 10 (TNFSF10), and proteolipid protein 1 (PLP1). PLP1 was validated to be up-regulated significantly in UFs both at mRNA and protein levels. The area under the ROC curve (AUC) of PLP1 was 0.956, with a sensitivity of 79.2% and a specificity of 100%. Conclusion: Overall, our results indicate that PLP1 may be a potential diagnostic biomarker for uterine fibroids.
A method of large DNA fragment enrichment for nanopore sequencing in region 22q11.2
Authors: Lei Yu-Qing , Xu Liang-Pu , Cao Hua , Wang Xin-Rui 
Published: October 2022

Background: 22q11.2 deletion syndrome (22q11.2DS) is a disorder caused when a small part of chromosome 22 is missing. Diagnosis is currently established by the identification of a heterozygous deletion at chromosome 22q11.2 through chromosomal microarray analysis or other genomic analyses. However, more accurate identification of the breakpoint contributes to a clearer understanding of the 22q11.2 deletion syndrome.Methods: In this study, we present a feasible nanopore sequencing method of 22q11.2 deletion. This DNA enrichment method—region-specific amplification (RSA)—is able to analyze the 22q11.2 deletion by specific amplification of an approximately 1-Mb region where the breakpoint might exist. RSA introduces universal primers into the target region DNA by a Y-shaped adaptor ligation and a single primer extension. The enriched products, completed by amplification with universal primers, are then processed by standard ONT ligation sequencing protocols.Results: RSA is able to deliver adequate coverage (&gt;98%) and comparable long reads (average length &gt;1 Kb) throughout the 22q11.2 region. The long nanopore sequencing reads, derived from three umbilical cord blood samples, have facilitated the identification of the breakpoint of the 22q11.2 deletion, as well as by Sanger sequencing.Conclusion: The Oxford Nanopore MinION sequencer can use RSA to sequence the target region 22q11.2; this method could also be used for other hard-to-sequence parts of the genome.
Exploring the molecular mechanisms and shared gene signatures between rheumatoid arthritis and diffuse large B cell lymphoma
Authors: Li Haoguang , Yu Le , Zhang Xiuling , Shang Jingjing , Duan Xinwang 
Published: October 2022

The relationship between rheumatoid arthritis (RA) and diffuse large B-cell lymphoma (DLBCL) is well characterized, but the molecular mechanisms underlying this association have not been clearly investigated. Our study aimed to identify shared gene signatures and molecular mechanisms between RA and DLBCL. We selected multiple Gene Expression Omnibus (GEO) datasets (GSE93272, GSE83632, GSE12453, GSE1919) to obtain gene expression levels and clinical information about patients with RA and DLBCL. Weighted gene co-expression network analysis (WGCNA) was used to research co-expression networks associated with RA and DLBCL. Subsequently, we performed enrichment analysis of shared genes and screened the most significant core genes. We observed expression of the screened target gene, galectin 2 (LGALS2), in DLBCL patients and its impact on patient prognosis. Finally, we analyzed the molecular functional mechanism of LGALS2 and observed its relationship with the immune response in DLBCL using single-sample Gene Set Enrichment Analysis (ssGSEA). WGCNA recognized two major modules for RA and DLBCL, respectively. Shared genes (551) were identified for RA and DLBCL by observing the intersection. In addition, a critical shared gene, LGALS2, was acquired in the validation tests. Next, we found that the expression level of LGALS2 gradually decreased with tumor progression in DLBCL and that increased expression of LGALS2 predicted a better prognosis for DLBCL patients. ssGSEA revealed that LGALS2 is involved in immune-related pathways and has a significant regulatory effect on human immune responses. Additionally, we observed that LGALS2 is closely related to the sensitivity of multiple chemotherapeutic drugs. There is extremely little research on the molecular mechanism of correlation between RA and DLBCL. Our study identified that LGALS2 is a potential therapeutic target and an immune-related biomarker for patients with RA and DLBCL.
Sentiment analysis of tweets on alopecia areata, hidradenitis suppurativa, and psoriasis: Revealing the patient experience
Authors: Lee Irene Tai-Lin , Juang Sin-Ei , Chen Steven T. , Ko Christine , Ma Kevin Sheng-Kai 
Published: October 2022

BackgroundChronic dermatologic disorders can cause significant emotional distress. Sentiment analysis of disease-related tweets helps identify patients’ experiences of skin disease.ObjectiveTo analyze the expressed sentiments in tweets related to alopecia areata (AA), hidradenitis suppurativa (HS), and psoriasis (PsO) in comparison to fibromyalgia (FM).MethodsThis is a cross-sectional analysis of Twitter users’ expressed sentiment on AA, HS, PsO, and FM. Tweets related to the diseases of interest were identified with keywords and hashtags for one month (April, 2022) using the Twitter standard application programming interface (API). Text, account types, and numbers of retweets and likes were collected. The sentiment analysis was performed by the R “tidytext” package using the AFINN lexicon.ResultsA total of 1,505 tweets were randomly extracted, of which 243 (16.15%) referred to AA, 186 (12.36%) to HS, 510 (33.89%) to PsO, and 566 (37.61%) to FM. The mean sentiment score was −0.239 ± 2.90. AA, HS, and PsO had similar sentiment scores (p = 0.482). Although all skin conditions were associated with a negative polarity, their average was significantly less negative than FM (p &lt; 0.0001). Tweets from private accounts were more negative, especially for AA (p = 0.0082). Words reflecting patients’ psychological states varied in different diseases. “Anxiety” was observed in posts on AA and FM but not posts on HS and PsO, while “crying” was frequently used in posts on HS. There was no definite correlation between the sentiment score and the number of retweets or likes, although negative AA tweets from public accounts received more retweets (p = 0.03511) and likes (p = 0.0228).ConclusionThe use of Twitter sentiment analysis is a promising method to document patients’ experience of skin diseases, which may improve patient care through bridging misconceptions and knowledge gaps between patients and healthcare professionals.
The SON2A2 score: A novel grading scale for predicting hemorrhage and outcomes after thrombolysis
Authors: Ren Yu , He Zhongxiang , Du Xiaoyan , Liu Jie , Zhou Li , Bai Xue , Chen Yue , Wu Bowen , Song Xiaosong , Zhao Libo , Yang Qin 
Published: October 2022

ObjectivesThis study aimed to develop a score including novel putative predictors for predicting the risk of sICH and outcomes after thrombolytic therapy with intravenous (IV) recombinant tissue-type plasminogen activator (r-tPA) in acute ischemic stroke patients.MethodsAll patients with acute ischemic stroke treated with IV r-tPA at three university-based hospitals in Chongqing, China, from 2014 to 2019 were retrospectively studied. Potential risk factors associated with sICH (NINDS criteria) were determined with multivariate logistic regression, and we developed our score according to the magnitude of logistic regression coefficients. The score was validated in another independent cohort. Area under the receiver operating characteristic curve (AUC-ROC) was used to assess the performance of the score. Calibration was evaluated using the Hosmer–Lemeshow goodness-of-fit method.ResultsThe SON2A2 score (0 to 8 points) consisted of history of smoking (no = 1, yes = 0, β = 0.81), onset-to-needle time (≥3.5 = 1,&lt;3.5=0, β = 0.74), NIH Stroke Scale on admission (&gt;10 = 2, ≤10 = 0, β = 1.22), neutrophil percentage (≥80.0% = 1, &lt;80% = 0, β = 0.81), ASPECT score (≤11 = 2, &gt;11 = 0, β = 1.30), and age (&gt;65 years = 1, ≤65 years = 0, β = 0.89). The SON2A2 score was strongly associated with sICH (OR 1.98; 95%CI 1.675–2.34) and poor outcomes (OR 1.89; 95%CI 1.68–2.13). AUC-ROC in the derivation cohort was 0.82 (95%CI 0.77–0.86). Similar results were obtained in the validation cohort. The Hosmer–Lemeshow test revealed that predicted and observed event rates in derivation and validation cohorts were very close.ConclusionThe SON2A2 score is a simple, efficient, quick, and easy-to-perform scale for predicting the risk of sICH and outcome after intravenous r-tPA thrombolysis within 4.5 h in patients with ischemic stroke, and risk assessment using this test has the potential for early and personalized management of this disease in high-risk patients.
Preoperative peripheral blood inflammatory markers especially the fibrinogen-to-lymphocyte ratio and novel FLR-N score predict the prognosis of patients with early-stage resectable extrahepatic cholangiocarcinoma
Authors: Li Shijie , Zhang Xingli , Lou Changjie , Gu Yuanlong , Zhao Juan 
Published: October 2022

BackgroundSystemic inflammation is important in the development of extrahepatic cholangiocarcinoma (ECC). The aim of this study was to compare the prognostic power of preoperative peripheral blood inflammatory markers and the novel FLR-N score in patients with resectable ECC.MethodsA total of 140 patients with resectable ECC and 140 healthy controls (HCs) were recruited for the study. The Mann−Whitney U test was used to evaluate the differences in inflammatory markers between groups. Kaplan−Meier and Cox regression analyses were used to evaluate the prognostic power of preoperative fibrinogen, albumin, prealbumin, bilirubin, neutrophils, lymphocytes, monocytes, platelets, fibrinogen-to-lymphocyte ratio (FLR), fibrinogen-to-albumin ratio (FAR), fibrinogen-to-prealbumin ratio (FPR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), FLR-neutrophil (FLR-N) score, and CA19-9 in patients with resectable ECC. Nomogram was developed based on the results of multivariate Cox analyses.ResultsPatients with resectable ECC had significantly higher levels of neutrophils, monocytes, fibrinogen, FLR, FAR, FPR, NLR, PLR, and MLR and lower levels of lymphocytes, albumin, and prealbumin than HCs (all P &lt; 0.01). Albumin, prealbumin, and FPR had a good ability to distinguish between ECC patients with total bilirubin &lt; 34 µmol/L and HCs (AUCs of 0.820, 0.827, and 0.836, respectively). Kaplan−Meier analysis showed that high neutrophil, fibrinogen, FLR, FAR, PLR, MLR, and FLR-N score values were associated with poor survival in patients with resectable ECC. Multivariate analyses indicated that neutrophils (P = 0.022), FLR (P = 0.040), FLR-N score (P &lt; 0.0001), and positive lymph node metastasis (P = 0.016) were independent factors for overall survival (OS). Nomogram were developed to predict OS for patients with ECC.ConclusionThe prognostic roles of inflammatory markers in patients with resectable ECC were different. The preoperative neutrophil count, FLR and FLR-N score could serve as noninvasive markers for predicting the prognosis of resectable ECC.
Serum cytokines predict efficacy and toxicity, but are not useful for disease monitoring in lung cancer treated with PD-(L)1 inhibitors
Authors: Schindler Hannah , Lusky Fabienne , Daniello Lea , Elshiaty Mariam , Gaissmaier Lena , Benesova Karolina , Souto-Carneiro Margarida , Angeles Arlou Kristina , Janke Florian , Eichhorn Florian , Kazdal Daniel , Schneider Marc , Liersch Stephan , Klemm Sarah , Schnitzler Paul , Stenzinger Albrecht , Sültmann Holger , Thomas Michael , Christopoulos Petros 
Published: October 2022

IntroductionPD-(L)1 inhibitors (IO) have improved the prognosis of non-small-cell lung cancer (NSCLC), but more reliable predictors of efficacy and immune-related adverse events (irAE) are urgently needed. Cytokines are important effector molecules of the immune system, whose potential clinical utility as biomarkers remains unclear.MethodsSerum samples from patients with advanced NSCLC receiving IO either alone in the first (1L, n=46) and subsequent lines (n=50), or combined with chemotherapy (ICT, n=108) were analyzed along with age-matched healthy controls (n=15) at baseline, after 1 and 4 therapy cycles, and at disease progression (PD). Patients were stratified in rapid progressors (RP, progression-free survival [PFS] &lt;120 days), and long-term responders (LR, PFS &gt;200 days). Cytometric bead arrays were used for high-throughput quantification of 20 cytokines and other promising serum markers based on extensive search of the current literature.ResultsUntreated NSCLC patients had increased levels of various cytokines and chemokines, like IL-6, IL-8, IL-10, CCL5, G-CSF, ICAM-1, TNF-RI and VEGF (fold change [FC]=1.4-261, p=0.026-9x10-7) compared to age-matched controls, many of which fell under ICT (FC=0.2-0.6, p=0.014-0.002), but not under IO monotherapy. Lower baseline levels of TNF-RI were associated with longer PFS (hazard ratio [HR]= 0.42-0.54; p=0.014-0.009) and overall survival (HR=0.28-0.34, p=0.004-0.001) after both ICT and IO monotherapy. Development of irAE was associated with higher baseline levels of several cytokines, in particular of IL-1β and angiogenin (FC=7-9, p=0.009-0.0002). In contrast, changes under treatment were very subtle, there were no serum correlates of radiologic PD, and no association between dynamic changes in cytokine concentrations and clinical outcome. No relationship was noted between the patients’ serologic CMV status and serum cytokine levels.ConclusionsUntreated NSCLC is characterized by increased blood levels of several pro-inflammatory and angiogenic effectors, which decrease under ICT. Baseline serum cytokine levels could be exploited for improved prediction of subsequent IO benefit (in particular TNF-RI) and development of irAE (e.g. IL-1β or angiogenin), but they are not suitable for longitudinal disease monitoring. The potential utility of IL-1/IL-1β inhibitors in the management and/or prevention of irAE in NSCLC warrants investigation.
Papillary renal neoplasm with reverse polarity with a favorable prognosis: Two cases report and literature review
Authors: Yuzhi Zuo , Zhen Liang , Yu Xiao , Boju Pan , Weigang Yan , Xingcheng Wu 
Published: October 2022

BackgroundPapillary Renal Neoplasm (PRN) with polarity inversion is a less common subtype of kidney cancer with an apparently recognizable morphology, distinct immunohistochemical profiles, and frequent KRAS mutations. It has been estimated to account 4% of previously diagnosed PRN.Case presentationThis is a retrospective case report of two patients diagnosed with PRNRP. Two males were found to have kidney mass accidentally through imaging examination in clinic. Both of the patients had no obvious discomfort and abnormal test indicators. Subsequently, they underwent partial nephrectomy in our center by the same surgeon and followed up closely with an impressive clinical outcome. The pathology reports indicated that their pathological features were consistent with PRNRP. The HE staining showed a monolayer of papillary or tubular structures, with small nuclei away from the cytoplasmic top of the basement membrane. The immunohistochemical results were GATA3 (+), vimentin (-).ConclusionOur case reports and literature review suggested that PRNRP should be separated from traditional PRN and partial nephrectomy is a robust modality for PRNRP. The morphological, immunohistochemical, and genetic information of the cases we presented would provide important material for PRNRP to become a distinct category with benign clinical outcome.
Disparities in access to care among patients with appendiceal or colorectal cancer and peritoneal metastases: A medicare insurance-based study in the United States
Authors: Aquina Christopher T. , Brown Zachary J. , Beane Joal D. , Ejaz Aslam , Cloyd Jordan M. , Eng Oliver S. , Monson John R.T. , Ruff Samantha M. , Kasumova Gyulnara G. , Adam Mohamed O. , Obeng-Gyasi Samilia , Pawlik Timothy M. , Kim Alex C. 
Published: October 2022

BackgroundPrior studies attempting to identify disparities in the care of patients with appendiceal (AC) or colorectal cancer (CRC) with peritoneal metastasis (PM) are limited to single-institution, highly selected patient populations. This observational cohort study sought to identify factors associated with specialty care for Medicare beneficiaries with AC/CRC-PM.Materials and methodsPatients &gt;65 years old in the United States diagnosed with AC/CRC and isolated PM were identified within the Medicare Standard Analytic File (2013-2017). Mixed-effects analyses assessed patient factors associated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) and outpatient consultation with a peritoneal surface malignancy (PSM) surgeon, and Cox proportional-hazards analysis compared 3-year overall survival (OS) between patients receiving CRS/HIPEC versus systemic therapy alone.ResultsAmong 7,653 patients, only 250 (3.3%) underwent CRS/HIPEC. Among those individuals who did not undergo CRS/HIPEC (N=7,403), only 475 (6.4%) had outpatient consultation with a PSM surgeon. Patient factors independently associated with lower odds of CRS/HIPEC and PSM surgery consultation included older age, greater comorbidity burden, higher social vulnerability index, and further distance from a PSM center (p&lt;0.05). CRS/HIPEC was independently associated with better 3-year OS compared with systemic therapy alone (HR=0.29, 95%CI=0.21-0.38).ConclusionAn exceedingly small proportion of Medicare beneficiaries with AC/CRC-PM undergo CRS/HIPEC or even have an outpatient consultation with a PSM surgeon. Significant disparities in treatment and access to care exist for patients with higher levels of social vulnerability and those that live further away from a PSM center. Future research and interventions should focus on improving access to care for these at-risk patient populations.
Zebrafish as a platform to evaluate the potential of lipidic nanoemulsions for gene therapy in cancer
Authors: Cascallar María , Hurtado Pablo , Lores Saínza , Pensado-López Alba , Quelle-Regaldie Ana , Sánchez Laura , Piñeiro Roberto , de la Fuente María 
Published: October 2022

Gene therapy is a promising therapeutic approach that has experienced significant groth in recent decades, with gene nanomedicines reaching the clinics. However, it is still necessary to continue developing novel vectors able to carry, protect, and release the nucleic acids into the target cells, to respond to the widespread demand for new gene therapies to address current unmet clinical needs. We propose here the use of zebrafish embryos as an in vivo platform to evaluate the potential of newly developed nanosystems for gene therapy applications in cancer treatment. Zebrafish embryos have several advantages such as low maintenance costs, transparency, robustness, and a high homology with the human genome. In this work, a new type of putrescine-sphingomyelin nanosystems (PSN), specifically designed for cancer gene therapy applications, was successfully characterized and demonstrated its potential for delivery of plasmid DNA (pDNA) and miRNA (miR). On one hand, we were able to validate a regulatory effect of the PSN/miR on gene expression after injection in embryos of 0 hpf. Additionally, experiments proved the potential of the model to study the transport of the associated nucleic acids (pDNA and miR) upon incubation in zebrafish water. The biodistribution of PSN/pDNA and PSN/miR in vivo was also assessed after microinjection into the zebrafish vasculature, demonstrating that the nucleic acids remained associated with the PSN in an in vivo environment, and could successfully reach disseminated cancer cells in zebrafish xenografts. Altogether, these results demonstrate the potential of zebrafish as an in vivo model to evaluate nanotechnology-based gene therapies for cancer treatment, as well as the capacity of the developed versatile PSN formulation for gene therapy applications.
A tool for screening potentially inappropriate prescribing in Chinese children
Authors: Li Siyu , Huang Liang , Zeng Linan , Yu Dan , Jia Zhi-Jun , Cheng Guo , Zhang Lingli 
Published: October 2022

Background: More than half of adverse drug events in pediatric patients are avoidable and blocking medication errors at the prescribing stage might be one of the most effective preventive measures.Objective: To form a tool (a series of criteria) for detecting potentially inappropriate prescriptions in children, promote clinical rational drug use and reduce risks of medication in children.Methods: Potentially inappropriate prescription propositions for children were collected through a systematic review. Then, the Delphi technique was adopted to form the final criteria. Panelists were asked to use a 5-point Likert scale to rate their agreement with each potentially inappropriate prescription proposition and were encouraged to add new propositions based on their clinical experience and knowledge. After 2 rounds of Delphi survey and propositions were fully revised and improved, the final criteria for identifying potentially inappropriate prescriptions in children were formed.Results: The final criteria for identifying potential inappropriate prescriptions in children has 136 propositions, which were divided into “criteria for children with non-specific diseases/conditions” (71 propositions: 68 for potentially inappropriate medication, 3 for potential prescribing omission) and “criteria for children with specific diseases/conditions” (65 propositions: 55 for potentially inappropriate medication, 10 for potential prescribing omission), according to whether the proposition was about identifying specific risks associated with one drug in children with a specific other diseases/conditions that do not exist in children with other diseases/conditions.Conclusion: A tool for screening potentially inappropriate prescriptions in children is formed to detect potentially inappropriate medication and prescribing omission in pediatrics and is available to all medical professionals liable to prescribe or dispense medicines to children.