bluuebunny/crossref_metadata_2025 huggingface dataset:
Data from Resistance to an Irreversible Epidermal Growth Factor Receptor (EGFR) Inhibitor in EGFR-Mutant Lung Cancer Reveals Novel Treatment Strategies
Authors: Yu Zhiwei , Boggon Titus J. , Kobayashi Susumu , Jin Cheng , Ma Patrick C. , Dowlati Afshin , Kern Jeffrey A. , Tenen Daniel G. , Halmos Balázs
Published: March 2023

Abstract
Patients with epidermal growth factor receptor (EGFR)–mutant non–small cell lung cancer derive significant clinical benefit from treatment with the EGFR tyrosine kinase inhibitors gefitinib and erlotinib. Secondary EGFR mutations such as EGFR T790M commonly lead to resistance to these agents, limiting their long-term efficacy. Irreversible EGFR inhibitors such as CL-387,785 can overcome resistance and are in clinical development, yet acquired resistance against these agents is anticipated. We carried out a cell-based, in vitro random mutagenesis screen to identify EGFR mutations that confer resistance to CL-387,785 using T790M-mutant H1975 lung adenocarcinoma cells. Mutations at several residues occurred repeatedly leading to functional resistance to CL-387,785. These variants showed uninhibited cell growth, reduced apoptosis, and persistent EGFR activation in the presence of CL-387,785 as compared with parental H1975 cells, thus confirming their role in resistance. A screen of alternative agents showed that both an alternative EGFR inhibitor and a cyclin-dependent kinase 4 inhibitor led to significant inhibition of cell growth of the resistant mutants, suggestive of potential alternative treatment strategies. These results identify novel mutations mediating resistance to irreversible EGFR inhibitors and reveal alternative strategies to overcome or prevent the development of resistance in EGFR-mutant non–small cell lung cancers. [Cancer Res 2007;67(21):10417–27]
Data from MAGE-A, mMage-b, and MAGE-C Proteins Form Complexes with KAP1 and Suppress p53-Dependent Apoptosis in MAGE-Positive Cell Lines
Authors: Yang Bing , O'Herrin Sean M. , Wu Jianqiang , Reagan-Shaw Shannon , Ma Yongsheng , Bhat Kumar M.R. , Gravekamp Claudia , Setaluri Vijayasaradhi , Peters Noel , Hoffmann F. Michael , Peng Hongzhuang , Ivanov Alexey V. , Simpson Andrew J.G. , Longley B. Jack
Published: March 2023

Abstract
The MAGE-A, MAGE-B, and MAGE-C protein families comprise the class-I MAGE/cancer testes antigens, a group of highly homologous proteins whose expression is suppressed in all normal tissues except developing sperm. Aberrant expression of class I MAGE proteins occurs in melanomas and many other malignancies, and MAGE proteins have long been recognized as tumor-specific targets; however, their functions have largely been unknown. Here, we show that suppression of class I MAGE proteins induces apoptosis in the Hs-294T, A375, and S91 MAGE-positive melanoma cell lines and that members of all three families of MAGE class I proteins form complexes with KAP1, a scaffolding protein that is known as a corepressor of p53 expression and function. In addition to inducing apoptosis, MAGE suppression decreases KAP1 complexing with p53, increases immunoreactive and acetylated p53, and activates a p53 responsive reporter gene. Suppression of class I MAGE proteins also induces apoptosis in MAGE-A–positive, p53wt/wt parental HCT 116 colon cancer cells but not in a MAGE-A–positive HCT 116 p53−/− variant, indicating that MAGE suppression of apoptosis requires p53. Finally, treatment with MAGE-specific small interfering RNA suppresses S91 melanoma growth in vivo, in syngenic DBA2 mice. Thus, class I MAGE protein expression may suppress apoptosis by suppressing p53 and may actively contribute to the development of malignancies and by promoting tumor survival. Because the expression of class I MAGE proteins is limited in normal tissues, inhibition of MAGE antigen expression or function represents a novel and specific treatment for melanoma and diverse malignancies. [Cancer Res 2007;67(20):9954–62]
Data from Ribosomal Protein S27-like, a p53-Inducible Modulator of Cell Fate in Response to Genotoxic Stress
Authors: Li Jingsong , Tan Jing , Zhuang Li , Banerjee Birendranath , Yang Xiaojing , Chau Jenny Fung Ling , Lee Puay Leng , Hande Manoor Prakash , Li Baojie , Yu Qiang
Published: March 2023

Abstract
Activation of the p53 tumor suppressor upon DNA damage elicits either cell cycle arrest or apoptosis, and the precise mechanism governing cell fate after p53 response has not been well defined. Through genomic analysis, we have identified the ribosomal protein S27-like (RPS27L) as a novel p53 transcriptional target gene. Although RPS27L mRNA levels were consistently induced after diverse p53 activating signals, its change in protein level was stimuli-dependent: it was up-regulated when cells were arrested in response to DNA-damaging agents Adriamycin or VP16 but was down-regulated when cells underwent apoptosis in response to antimetabolite agent 5-fluorouracil. RPS27L is a nuclear protein that forms nuclear foci upon DNA damage. Depletion of RPS27L resulted in deficiency in DNA damage checkpoints, leading to conversion of DNA damage–induced p53 response from cell cycle arrest to apoptosis. We further show that RPS27L positively regulates p21 protein expression. Through this mechanism, RPS27L induction by p53 facilitates p21-mediated cell cycle arrest and protects against DNA damage–induced apoptosis. Thus, RPS27L modulates DNA damage response and functions as a part of the control switch to determine cell fate to DNA damage–p53 response. [Cancer Res 2007;67(23):11317–26]
Data from Repair of 2′-C-Cyano-2′-Deoxy-1-β-d-arabino-Pentofuranosylcytosine–Induced DNA Single-Strand Breaks by Transcription-Coupled Nucleotide Excision Repair
Authors: Wang Yaqing , Liu Xiaojun , Matsuda Akira , Plunkett William
Published: March 2023

Abstract
The cytosine nucleoside analogue 2′-C-cyano-2′-deoxy-1-β-d-arabino-pentofuranosylcytosine (CNDAC) causes DNA single-strand breaks after its incorporation into DNA. This investigation sought to determine if DNA excision repair pathways were activated to repair this damage. Neither the base excision repair nor the mismatch repair pathway seemed to be involved. Cells deficient in the CSB protein, which initiates transcription-coupled nucleotide excision repair (NER) pathway (TC-NER), exhibited increased clonogenic sensitivity to CNDAC, whereas cells deficient in XPC, which initiates global genome NER, were slightly resistant relative to wild-type cells. The cells lacking either helicase XPB, which unwinds 5′ of the lesion, or endonuclease XPF, which incises 5′ to a lesion, exhibited increased clonogenic sensitivity to CNDAC, as did cells lacking the XPF partner protein ERCC1. This sensitization was independent of p53 function. Repletion of XPF restored sensitivity comparable with the wild type. In contrast, cells lacking either XPD, the 3′-helicase, or the 3′-endonuclease XPG were equally as sensitive as wild-type cells. In comparison, cells deficient in XPF were not sensitized to other cytosine nucleoside analogues, troxacitabine and cytarabine. Thus, the single-strand nick caused by CNDAC is recognized and, in part, repaired by the TC-NER pathway. NER proteins that function in the 5′ direction relative to the UV-induced lesion also participate in the repair of the CNDAC-induced nick, in contrast to proteins that process on the 3′ side of the lesion. [Cancer Res 2008;68(10):3881–9]
Data from Eradication of Solid Human Breast Tumors in Nude Mice with an Intravenously Injected Light-Emitting Oncolytic Vaccinia Virus
Authors: Zhang Qian , Yu Yong A. , Wang Ena , Chen Nanhai , Danner Robert L. , Munson Peter J. , Marincola Francesco M. , Szalay Aladar A.
Published: March 2023

Abstract
Previously, we reported that a recombinant vaccinia virus (VACV) carrying a light-emitting fusion gene enters, replicates in, and reveals the locations of tumors in mice. A new recombinant VACV, GLV-1h68, as a simultaneous diagnostic and therapeutic agent, was constructed by inserting three expression cassettes (encoding Renilla luciferase–Aequorea green fluorescent protein fusion, β-galactosidase, and β-glucuronidase) into the F14.5L, J2R (encoding thymidine kinase) and A56R (encoding hemagglutinin) loci of the viral genome, respectively. I.v. injections of GLV-1h68 (1 × 107 plaque-forming unit per mouse) into nude mice with established (∼300–500 mm3) s.c. GI-101A human breast tumors were used to evaluate its toxicity, tumor targeting specificity, and oncolytic efficacy. GLV-1h68 showed an enhanced tumor targeting specificity and much reduced toxicity compared with its parental LIVP strains. The tumors colonized by GLV-1h68 exhibited growth, inhibition, and regression phases followed by tumor eradication within 130 days in 95% of the mice tested. Tumor regression in live animals was monitored in real time based on decreasing light emission, hence demonstrating the concept of a combined oncolytic virus–mediated tumor diagnosis and therapy system. Transcriptional profiling of regressing tumors based on a mouse-specific platform revealed gene expression signatures consistent with immune defense activation, inclusive of IFN-stimulated genes (STAT-1 and IRF-7), cytokines, chemokines, and innate immune effector function. These findings suggest that immune activation may combine with viral oncolysis to induce tumor eradication in this model, providing a novel perspective for the design of oncolytic viral therapies for human cancers. [Cancer Res 2007;67(20):10038–46]
Data from Transmembrane Protein 18 Enhances the Tropism of Neural Stem Cells for Glioma Cells
Authors: Jurvansuu Jaana , Zhao Ying , Leung Doreen S.Y. , Boulaire Jerome , Yu Yuan Hong , Ahmed Sohail , Wang Shu
Published: March 2023

Abstract
The failure of current glioma therapies is mainly due to the ability of the tumor cells to invade extensively the surrounding healthy brain tissue, hence escaping localized treatments. Neural stem cells (NSC) are able to home in on tumor foci at sites distant from the main tumor mass, possibly enabling treatment of scattered glioma clusters. To make the strategy more effective, we performed a cDNA expression library screening to identify the candidate genes that once overexpressed would enhance the tropism of NSCs for gliomas. Here, we show that a previously unannotated gene, the one encoding transmembrane protein 18 (TMEM18), is one such gene. Overexpression of TMEM18 was seen in the current study to provide NSCs and neural precursors an increased migration capacity toward glioblastoma cells in vitro and in the rat brain. Functional inactivation of the TMEM18 gene resulted in almost complete loss of the migration activity of these cells. Thus, TMEM18 is a novel cell migration modulator. Overexpression of this protein could be favorably used in NSC-based glioma therapy. [Cancer Res 2008;68(12):4614–22]
Data from Methylation Silencing of Transforming Growth Factor-β Receptor Type II in Rat Prostate Cancers
Authors: Yamashita Satoshi , Takahashi Satoru , McDonell Nathalie , Watanabe Naoko , Niwa Tohru , Hosoya Kosuke , Tsujino Yoshimi , Shirai Tomoyuki , Ushijima Toshikazu
Published: March 2023

Abstract
To identify methylation-silenced genes in prostate cancers, a microarray analysis for genes up-regulated by treatment with a demethylating agent, 5-aza-2′-deoxycytidine, was performed using three rat prostate cancer cell lines. Eight genes (Aebp1, Dysf, Gas6, LOC361288, Nnat, Ocm, RGD1308119, and Tgfbr2) were re-expressed at 16-fold or more, and their promoter CpG islands were shown to be densely methylated in the cancer cell lines. From the eight genes, Tgfbr2, a key mediator of transforming growth factor-β (TGF-β) signaling that has been strongly implicated in human and rat prostate carcinogenesis, was selected, and its silencing in primary samples was analyzed further. Tgfbr2 was methylated and markedly down-regulated in three of seven 3,2′-dimethyl-4-aminobiphenyl–induced invasive adenocarcinomas in the dorsolateral lobe of the rat prostate. In humans, marked down-regulation of TGFBR2 protein was observed in 12 of 20 high-grade prostatic intraepithelial neoplasia and 36 of 60 prostate cancers. DNA methylation of the human TGFBR2 promoter CpG islands repressed transcription, if present, but neither methylation nor mutation were detected in 27 human prostate cancers analyzed. Methylation silencing of rat Tgfbr2 was associated with histone H3 lysine 9 trimethylation, whereas decreased expression of human TGFBR2 was mainly due to decreased transcription activity, sometimes in concert with histone deacetylation and H3 lysine 27 trimethylation. The identification of methylation silencing of Tgfbr2 in rat prostate cancers, in accordance with TGFBR2 down-regulation in human prostate cancers, will enable us to analyze how aberrant methylation is induced in vivo and identify factors that promote and suppress the induction of aberrant methylation. [Cancer Res 2008;68(7):2112–21]
Data from NOTCH Is Part of the Transcriptional Network Regulating Cell Growth and Survival in Mouse Plasmacytomas
Authors: Shin Dong-Mi , Shaffer Daniel J. , Wang Hongsheng , Roopenian Derry C. , Morse Herbert C.
Published: March 2023

Abstract
Aside from Myc-activating translocations characteristic of plasmacytomas (PCT), little is known about genetic factors and signaling pathways responsible for the development of spontaneous B-cell lineage lymphomas of mice. Here, we characterized the transcriptional profiles of PCT, centroblastic diffuse large B-cell lymphomas (CBL), and high-grade splenic marginal zone B-cell lymphoma (MZL++) using high-throughput quantitative reverse transcription-PCR. Expression profiles of CBL and MZL++ were strikingly similar and quite unlike that of PCT. Among the genes expressed at significantly higher levels by PCT were a number involved in NOTCH signaling, a finding supported by gene set enrichment analyses of microarray data. To investigate the importance of this pathway, NOTCH signaling was blocked in PCT cell lines by treatment with a γ-secretase inhibitor (GSI) or transduction of a dominant-negative mutant of MAML1. These treatments resulted in reduced expression of NOTCH transcriptional targets in association with impaired proliferation and increased apoptosis. GSI treatment of transformed plasma cells in a primary PCT also induced apoptosis. These results integrate NOTCH activation with oncogenic signaling pathways downstream of translocated Myc in the pathogenesis of mouse PCT, two signaling pathways also implicated in development of human multiple myeloma and T-cell lymphoblastic lymphoma. [Cancer Res 2008;68(22):9202–11]
Data from The Signatures of Autozygosity among Patients with Colorectal Cancer
Authors: Bacolod Manny D. , Schemmann Gunter S. , Wang Shuang , Shattock Richard , Giardina Sarah F. , Zeng Zhaoshi , Shia Jinru , Stengel Robert F. , Gerry Norman , Hoh Josephine , Kirchhoff Tomas , Gold Bert , Christman Michael F. , Offit Kenneth , Gerald William L. , Notterman Daniel A. , Ott Jurg , Paty Philip B. , Barany Francis
Published: March 2023

Abstract
Previous studies have shown that among populations with a high rate of consanguinity, there is a significant increase in the prevalence of cancer. Single nucleotide polymorphism (SNP) array data (Affymetrix, 50K XbaI) analysis revealed long regions of homozygosity in genomic DNAs taken from tumor and matched normal tissues of colorectal cancer (CRC) patients. The presence of these regions in the genome may indicate levels of consanguinity in the individual's family lineage. We refer to these autozygous regions as identity-by-descent (IBD) segments. In this study, we compared IBD segments in 74 mostly Caucasian CRC patients (mean age of 66 years) to two control data sets: (a) 146 Caucasian individuals (mean age of 80 years) who participated in an age-related macular degeneration (AMD) study and (b) 118 cancer-free Caucasian individuals from the Framingham Heart Study (mean age of 67 years). Our results show that the percentage of CRC patients with IBD segments (≥4 Mb length and 50 SNPs probed) in the genome is at least twice as high as the AMD or Framingham control groups. Also, the average length of these IBD regions in the CRC patients is more than twice the length of the two control data sets. Compared with control groups, IBD segments are found to be more common among individuals of Jewish background. We believe that these IBD segments within CRC patients are likely to harbor important CRC-related genes with low-penetrance SNPs and/or mutations, and, indeed, two recently identified CRC predisposition SNPs in the 8q24 region were confirmed to be homozygous in one particular patient carrying an IBD segment covering the region. [Cancer Res 2008;68(8):2610–21]
Data from Glioma Pathogenesis-Related Protein 1 Exerts Tumor Suppressor Activities through Proapoptotic Reactive Oxygen Species–c-Jun–NH2 Kinase Signaling
Authors: Li Likun , Abdel Fattah ElMoataz , Cao Guangwen , Ren Chengzhen , Yang Guang , Goltsov Alexei A. , Chinault A. Craig , Cai Wei-Wen , Timme Terry L. , Thompson Timothy C.
Published: March 2023

Abstract
Glioma pathogenesis-related protein 1 (GLIPR1), a novel p53 target gene, is down-regulated by methylation in prostate cancer and has p53-dependent and -independent proapoptotic activities in tumor cells. These properties suggest an important tumor suppressor role for GLIPR1, yet direct genetic evidence of a tumor suppressor function for GLIPR1 is lacking and the molecular mechanism(s), through which GLIPR1 exerts its tumor suppressor functions, has not been shown. Here, we report that the expression of GLIPR1 is significantly reduced in human prostate tumor tissues compared with adjacent normal prostate tissues and in multiple human cancer cell lines. Overexpression of GLIPR1 in cancer cells leads to suppression of colony growth and induction of apoptosis. Mice with an inactivated Glipr1 gene had significantly shorter tumor-free survival times than either Glipr1+/+ or Glipr1+/− mice in both p53+/+ and p53+/− genetic backgrounds, owing to their development of a unique array of malignant tumors. Mechanistic analysis indicated that GLIPR1 up-regulation increases the production of reactive oxygen species (ROS) leading to apoptosis through activation of the c-Jun–NH2 kinase (JNK) signaling cascade. Thus, our results identify GLIPR1 as a proapoptotic tumor suppressor acting through the ROS-JNK pathway and support the therapeutic potential for this protein. [Cancer Res 2008;68(2):434–43]
Data from Subtypes of Breast Cancer Show Preferential Site of Relapse
Authors: Smid Marcel , Wang Yixin , Zhang Yi , Sieuwerts Anieta M. , Yu Jack , Klijn Jan G.M. , Foekens John A. , Martens John W.M.
Published: March 2023

Abstract
We explored whether the five previously reported molecular subtypes in breast cancer show a preference for organ-specific relapse and searched for molecular pathways involved. The “intrinsic” gene list describing the subtypes was used to classify 344 primary breast tumors of lymph node–negative patients. Fisher exact tests were used to determine the association between a tumor subtype and a particular site of distant relapse in these patients who only received local treatment. Modulated genes and pathways were identified in the various groups using Significance Analysis of Microarrays and Global Testing. Bone relapse patients were most abundant in the luminal subtypes but were found less than expected in the basal subtype. The reverse was true for lung and brain relapse patients with the remark that absence of lung relapse was luminal A specific. Finally, a pleura relapse, although rare, was found almost exclusively in both luminal subtypes. Many differentially expressed genes were identified, of which several were in common in a subtype and the site to which the subtype preferentially relapsed. WNT signaling was up-regulated in the basal subtype and in brain-specific relapse, and down-modulated in the luminal B subtype and in bone-specific relapse. Focal adhesion was found up-regulated in the luminal A subtype but down-regulated in lung relapse. The five major molecular subtypes in breast cancer are evidently different with regard to their ability to metastasize to distant organ(s), and share biological features and pathways with their preferred distant metastatic site. [Cancer Res 2008;68(9):3108–14]
Data from TGFBI Deficiency Predisposes Mice to Spontaneous Tumor Development
Authors: Zhang Ye , Wen Gengyun , Shao Genze , Wang Cuidong , Lin Chyuansheng , Fang Hongbo , Balajee Adayabalam S. , Bhagat Govind , Hei Tom K. , Zhao Yongliang
Published: March 2023

Abstract
Loss of TGFBI, a secreted protein induced by transforming growth factor-β, has been implicated in cell proliferation, tumor progression, and angiogenesis by in vitro studies. However, in vivo antitumor functions of TGFBI as well as the underlying molecular mechanism are not well understood. To these aims, we have generated a mouse model with disruption of TGFBI genomic locus. Mice lacking TGFBI show a retarded growth and are prone to spontaneous tumors and 7,12-dimethylbenz(a)anthracene–induced skin tumors. In relation to wild-type (WT) mouse embryonic fibroblasts (MEF), TGFBI−/− MEFs display increased frequencies of chromosomal aberration and micronuclei formation and exhibit an enhanced proliferation and early S-phase entry. Cyclin D1 is up-regulated in TGFBI−/− MEFs, which correlates with aberrant activation of transcription factor cyclic AMP–responsive element binding protein (CREB) identified by chromatin immunoprecipitation and luciferase reporter assays. TGFBI reconstitution in TGFBI−/− cells by either retroviral infection with WT TGFBI gene or supplement with recombinant mouse TGFBI protein in the culture medium leads to the suppression of CREB activation and cyclin D1 expression, and further inhibition of cell proliferation. Cyclin D1 up-regulation was also identified in most of the tumors arising from TGFBI−/− mice. Our studies provide the first evidence that TGFBI functions as a tumor suppressor in vivo. [Cancer Res 2009;69(1):37–44]
Risk Factors for Intraoperative Hypothermia during Holmium Laser Enucleation of the Prostate
Authors: Morishige Sae , Ohyama Takehiro , Fujita Nobuko , Kameda Megumi , Yonekura Yuuki , Endo Fumiyasu , Abe Seiki
Published: March 2023

Introduction: Holmium laser enucleation of the prostate (HoLEP) is considered a size-independent gold standard for benign prostatic hyperplasia (BPH), and there is no upper limit of prostate weight that can be treated. Tissue retrieval can be time-consuming in cases of significant prostatic enlargement, which may lead to intraoperative hypothermia. As there are few studies on perioperative hypothermia in HoLEP, we conducted a retrospective study of patients who underwent HoLEP at our hospital. Methods: The data of 147 patients who underwent HoLEP at our hospital were retrospectively collected and analyzed for the occurrence of intraoperative hypothermia (temperature <36°C); age, body mass index (BMI), anesthesia method, body temperature, total fluid infusion, operation time, and irrigation fluid were the explanatory variables. Results: Intraoperative hypothermia was observed in 46 of 147 patients (31.3%). Simple logistic regression analysis showed that age (odds ratio [OR]: 1.07, 95% confidence interval [CI]: 1.01–1.13, p = 0.021), BMI (OR: 0.84, 95% CI: 0.72–0.96, p = 0.017), spinal anesthesia (OR: 4.92, 95% CI: 1.86–14.99, p = 0.002), and surgical time (OR: 1.04, 95% CI: 1.01–1.06, p = 0.006) were predictors of hypothermia. The decrease in body temperature was more pronounced with longer-duration surgery and reached 0.58°C at 180 min. Conclusion: General anesthesia, instead of spinal anesthesia, is recommended in high-risk patients with advanced age or low BMI to avoid intraoperative hypothermia during HoLEP. Two-stage morcellation may be considered for large adenomas, when a prolonged operative time and hypothermia are anticipated.
Component-Resolved Analyses for Diagnosis of Food Allergies in Infants and Young Children in Southern China
Authors: An Nairui , Gan Hui , Huang Zhifeng , Zhang Teng , Cheng Zhangkai J. , Zhu Huiqing , Liu Tingting , Lin Xiaomin , Sun Baoqing
Published: March 2023

Introduction: Chicken eggs and cow’s milk are two of the most common foods that cause allergic reactions in infants and young children, and there is a lack of precise diagnostic methods to identify the allergic state of these patients. The recently developed food allergen component-resolved diagnosis (CRD) may be a more accurate diagnosis method for food allergies. Methods: One hundred children sensitized to egg white and milk crude extracts and diagnosed with or suspected allergic disease were included. The specific immunoglobulin E (sIgE) (s) of animal food allergen crude extracts (egg yolk, milk, shrimp, crab, cod, beef) and the main components of egg white and milk were tested. The sensitization characteristics, cross-reactivity, and clinical relevance were analyzed. Results: The results of egg white-sensitized patients showed that ovalbumin (Gal d 2) had the highest positive rate of 100%. Compared with other pairwise combinations of egg allergens, the combination of egg white and Gal d 2 had higher diagnostic accuracy, with an AUC of 0.876 (95% CI: 0.801–0.951), a sensitivity of 88.9%, and a specificity of 75.9%. The positive rates of beta-lactoglobulin (Bos d 5) and alpha-lactoglobulin (Bos d 4) in the milk-sensitized children were comparable, 92% and 91%, respectively. The combination of crude milk extract and Bos d 4 had the highest diagnostic accuracy, with an AUC of 0.969 (95% CI: 0.938–0.999), a sensitivity of 100%, and a specificity of 82.7%. Conclusion: Among these subjects, our study found the main allergenic component of egg white was Gal d 2, and the main allergenic components of milk were Bos d 4 and Bos d 5. CRD may help identify egg/milk allergies and non-allergies.
Early Predictors of Infected Pancreatic Necrosis in Severe Acute Pancreatitis: Implications of Neutrophil to Lymphocyte Ratio, Blood Procalcitonin Concentration, and Modified CT Severity Index
Authors: Zhu Qing-Yun , Li Ruo-Meng , Zhu Yun-Peng , Hao Dong-Liang , Liu Yan , Yu Jing , Yang Xue , Zhang Yu-Shi , Lin Tian-Jiao , Yan Xu , Zuo Jian-Xin , Pan Xin-Ting
Published: March 2023

Background: Infected pancreatic necrosis (IPN) accounts for 30% mortality in severe acute pancreatitis (SAP). Early prediction of IPN occurrence is critical for prophylactic measures to be taken. This study aimed to evaluate the predicting value for IPN of combined markers at early stages of SAP. Methods: The clinical records of 324 SAP patients admitted within 48 h after disease onset were retrospectively analyzed. As potential predictors, the neutrophil to lymphocyte ratio (NLR), blood procalcitonin (PCT) concentration on the 1st, 4th, and 7th day post admission, as well as modified computerized tomography severity index (MCTSI) on the 5–7th day post admission, were extracted. Correlations between these features with IPN were analyzed using logistic regression, and predictive values were estimated using the receiver operating characteristic curve analyses. Results: NLR, PCT, body mass index, and MCTSI were significantly higher in the IPN group (p < 0.001) compared to the control, among which NLR, PCT, and MCTSI were identified as independent predictors for IPN in logistic regression model. Combination of these parameters yielded significant predicting values with an area under curve of 0.92, sensitivity of 97.2%, and specificity of 77.2% in receiver operating characteristic curve analysis. Conclusion: Combination of NLR, PCT, MCTSI might facilitate the prediction of IPN occurrence in SAP patients.
A Missense Pathogenic Variant in a Conserved Region of CNTNAP2 Is Associated with Obesity, Seizures, and Language Impairment in a Pakistani Family
Authors: Naudhani Sara , Ahmad Adeel , Khan Bazai Fariya , Pervez Muhammad Tariq , Zafar Azqa , Shah Sajjad Ali , Raheem Nafeesa , Baloch Abdul Hameed , Mushtaq Muhammad , Daud Shakeela
Published: March 2023

Introduction: In a consanguineous family, seven siblings born in three sibships showed a syndromic disorder characterized by obesity, seizures, and language impairment phenotypes, which appeared at early age or developed during early childhood. Methods: By whole-exome sequencing and subsequent Sanger sequencing, a novel homozygous missense variant (c.3371 T>A [p.Ile1124Asn]) in exon 20 of the CNTNAP2 gene was identified. Results: The pathogenic variant in this family is located within one of the laminin G-like 4 domains of CASPR2 and may cause loss of hydrophobic interactions of CASPR2 with its partner proteins. Single nucleotide and copy number variants in this gene have previously been related to Gilles de la Tourette syndrome, cortical dysplasia-focal epilepsy syndrome, schizophrenia, Pitt-Hopkins syndrome, and autism spectrum, attention deficit hyperactivity, and obsessive compulsive disorders. Yet, few studies described patients with CNTNAP2 variants showing diet-induced obesity. Conclusion: This report expands the phenotypic spectrum of this rare syndrome and provides deeper insights by documenting the clinical features and genetic findings of the patients.
Association between Polyunsaturated Fatty Acid Intake and Eczema in Children and Adolescents
Authors: Zhang Bin , Li Ping , Fu Peijun
Published: March 2023

Introduction: Eczema is a common allergic skin condition among children and adolescents, and polyunsaturated fatty acids (PUFAs) are a kind of fatty acid which were reported to be associated with reduced risk of eczema. Previous studies explored different types of PUFAs with various age groups of children and adolescents, and the influence of confounding factors such as medicine use was not considered. In the present study, we aimed to identify the associations between PUFAs and the risk of eczema in children and adolescents. These findings of our study might help better understand the associations between PUFAs and eczema. Methods: This cross-sectional study collected the data of 2,560 children and adolescents aged 6–19 years from National Health and Nutrition Examination Surveys (NHANES) between 2005 and 2006. Total PUFA, omega-3 (n-3), including octadecatrienoic acid/18:3, octadecatrienoic acid/18:4, eicosapentaenoic acid/20:5, docosapentaenoic acid/22:5, and docosahexaenoic acid/22:6, omega-6 (n-6), including octadecatrienoic acid/18:2 and eicosatetraenoic acid/20:4, total n-3 intake, total n-6 intake, and n-3/n-6 were main variables in this study. Univariate logistic regression was applied for identifying potential confounders for eczema. Univariate and multivariate logistic regression analysis were conducted to explore the associations between PUFAs and eczema. Subgroup analysis was performed on subjects with different ages, and patients complicated with other allergic diseases, allergy, and medicine use or not. Results: In total, there were 252 (9.8%) subjects who had eczema. After adjusting for confounding factors including age, race, poverty to income ratio (PIR), medicine use, hay fever, sinus infection, body mass index (BMI), serum total immunoglobulin E (IgE) antibody, and IgE, we observed that eicosatetraenoic acid/20:4 (OR = 0.17, 95% CI: 0.04–0.68) and total n-3 (OR = 0.88, 95% CI: 0.77–0.99) were linked with decreased risk of eczema in children and adolescents. Eicosatetraenoic acid/20:4 was correlated with decreased risk of eczema in participants without hay fever (OR = 0.82, 95% CI: 0.70–0.97) and medicine use (OR = 0.80, 95% CI: 0.68–0.94) or with allergy (OR = 0.75, 95% CI: 0.59–0.94). Total n-3 intake was associated with a reduced risk of eczema with the adjusted OR of 0.84, 95% CI: 0.72–0.98) in participants without hay fever. In those without sinus infection, octadecatrienoic acid/18:4 was linked with decreased risk of eczema (OR = 0.83, 95% CI: 0.69–0.99). Conclusion: N-3 and eicosatetraenoic acid/20:4 might be associated with the risk of eczema in children and adolescents.
Surgical Approaches for Possible Positions of an Olfactory Implant to Stimulate the Olfactory Bulb
Authors: Menzel Susanne , Konstantinidis Iordanis , Valentini Marco , Battaglia Paolo , Turri-Zanoni Mario , Sileo Giorgio , Monti Giulia , Castelnuovo Paolo Giocondo Maria , Hummel Thomas , Macchi Alberto
Published: March 2023

Introduction: Current scientific developments seem to allow for an “olfactory implant” in analogy to cochlear implants. However, the position and surgical approaches for electrical stimulation of the olfactory system are unclear. Methods: In a human anatomic cadaver study, we investigated different endoscopic approaches to electrically stimulate the olfactory bulb (OB) based on the following considerations: (1) the stimulating electrode should be close to the OB. (2) The surgical procedure should be as non-invasive and safe as possible and (3) as easy as possible for an experienced ENT surgeon. Results: In summary, the endoscopic intracranial positioning of the electrode via a widened ostium of the fila olfactoria or a frontal sinus surgery like a Draf IIb procedure is a good option in terms of patients’ risk, degree of difficulty for ENT surgeons, and position to the OB. Endoscopic intranasal positioning appeared to be the best option in terms of patient risk and the degree of difficulty for ENT surgeons. Although a bigger approach to the OB using a drill and the combined intranasal endoscopic and external approach enabled a close placement of the electrode to the OB, they do not seem relevant in practice due to their higher invasiveness. Conclusion: The study suggested that an intranasal positioning of a stimulating electrode is possible, with placements beneath the cribriform plate, extra- or intracranially, applying elegant surgical techniques with low or medium risk to the patient and a close placement to OB.
Accreditation Impact on Quality of Healthcare Organization Services and Culture in a Tertiary Hospital in Saudi Arabia
Authors: Babakkor Mohammed A. , Kattan Waleed M.
Published: March 2023

Introduction: While accreditation is thought to promote healthcare quality, a literature review revealed a scarcity of studies conducted in Saudi Arabia addressing the relationship between accreditation and better care quality and healthcare organization culture. Objectives: This research examined the accreditation effect on care quality and culture presented in King Abdullah Medical City (KAMC), as a healthcare organization, from the perspective of healthcare workers. Methods: The study design is a cross-sectional quantitative using anonymous and self-administered questionnaire for data collection from healthcare employees. The total number of participants was 218. Descriptive analysis was used, including means, range, and standard deviation. Also, the χ2 test was used for the association between the variables. Results: The result of the study showed that most of the dimensions associated with quality of care received high ratings. It revealed a significant beneficial association between employees’ perceptions of accreditation and quality of care across all these dimensions. The most dominant culture at KAMC was a group type demonstrated KAMC to be a personal environment. It revealed a strong relationship between employees’ views of the accreditation effect and a group culture type. Conclusion: This study’s findings matched those of a literature review that revealed a relation between accreditation and quality. Accreditation can help foster an organizational culture changing toward a culture that values skill development, cooperation, outcomes quality, and customer satisfaction. Accreditation processes have been found to promote a long-lasting and sustained improvement in quality of care and culture change. It demonstrated the crucial leadership influences in reaching this goal.
Changes in QT Interval in Maintenance Hemodialysis Patients: Pre-Dialysis, One Hour after Initiation of Dialysis, and Post-Dialysis
Authors: Nguyen Van Thanh , Pham Bui Van , Le Thao Thi Thu , Vo Chien Duc , Nguyen Dung Quang , Tran Nguyen Ngoc
Published: March 2023

Introduction: This study aimed to evaluate the effects of dialysis on change of QT interval in pre-dialysis, 1 h after dialysis initiation, and post-dialysis period in patients on maintenance dialysis (MHD). Methods: An observational prospective study was conducted, including 61 patients, on thrice-weekly MHD ≥3 months, and without acute diseases, at the Nephrology-Dialysis Department of a tertiary hospital in Vietnam. The exclusive criteria were atrial fibrillation, atrial flutter, branch block, prolonged QT recorded in medical history, and taking antiarrhythmic drugs lengthening QT interval before entering the study. Twelve-lead electrocardiographs and blood chemistries were done simultaneously before, 1 h after initiation, and after the dialysis session. Results: The proportion of patients with prolonged QT interval increased significantly from 44.3% in pre-dialysis to 77% 1 h after dialysis initiation and 86.9% in post-dialysis session. Immediately after dialysis, the QT and QTc intervals on all 12 leads were significantly longer. Post-dialysis levels of potassium, chloride, magnesium, and urea decreased significantly from 3.97 (0.7), 98.6 (4.7), 1.04 (0.2), and 21.4 (6.1) to 2.78 (0.4), 96.6 (2.5), 0.87 (0.2), and 6.33 (2.8) mmol/L, respectively, whereas the calcium increased significantly from 2.19 (0.2) to 2.57 (0.2) mmol/L. There were significant differences in the potassium level at the dialysis initiation and its speed of reduction between the group without and with prolonged QT interval. Conclusions: There was an increased risk of prolonged QT interval in MHD patients regardless of the absence of the previous abnormal QT interval. Notably, this risk increased rapidly 1 h after the initiation of dialysis.
Examination of the Effect of Switching Dialysis Membranes on the Immune Response to Influenza Virus Vaccination in Hemodialysis Patients
Authors: Tomo Tadashi , Takei Mitsuo , Matsuyama Makoto , Matsuyama Iehisa , Matsuyama Kazuhiro
Published: March 2023

Introduction: In this study, we examined the effect of switching dialysis membranes on the response to influenza virus vaccination in HD patients. Methods: This study consisted of two phases. In phase 1, antibody titers were measured and compared between HD patients and healthy volunteers (HVs) before and after vaccination against influenza virus. Using antibody titers 4 weeks after vaccination, HD patients and HVs were classified according to seroconversion (i.e., antibody titers against all four strains were >20-fold) or non-seroconversion (i.e., antibody titer against at least one strain was <20-fold). In the phase 2, we examined whether the change in the dialysis membrane from a polysulfone (PS) to a polymethyl methacrylate (PMMA) membrane affected the response to vaccination in HD patients without seroconversion in response to the vaccine the previous year. Patients with seroconversion and non-seroconversion were classified as responders and nonresponders, respectively. Additionally, we compared clinical data. Results: In the phase 1, 110 HD patients and 80 HVs were enrolled, and their seroconversion rates were 58.6% and 72.5%, respectively. In the phase 2, 20 HD patients without seroconversion in response to the vaccine the previous year were enrolled, and the dialyzer membrane was changed to PMMA 5 months before annual vaccination. After annual vaccination, 5 and 15 HD patients were categorized as responders and nonresponders, respectively. In the responders, β2-microglobulin, white blood cell counts, platelet counts, and serum albumin levels (Alb) were all higher than in the nonresponders. Conclusion: The responsiveness to vaccination against influenza virus was lower in HD patients compared with HVs. Changing the dialysis membrane from PS to PMMA appeared to affect the response to vaccination in HD patients.
Case Series of Frontal Fibrosing Alopecia and Fibrosing Alopecia in a Pattern Distribution: Is There a Familial Correlation?
Authors: Gavazzoni Dias Maria Fernanda Reis , Lofeu Cury Amanda , Vilar Enoi Aparecida Guedes , Peixoto Patricia Guimarães , Ekelem Chloe
Published: March 2023

Introduction: Frontal Fibrosing Alopecia (FFA) and Fibrosing Alopecia in a Pattern Distribution (FAPD) are two distinct entities of cicatricial pattern hair loss that share histological features of perifollicular lichenoid inflammation associated with concentric fibrosis. Although the pathophysiology of FFA and FAPD are still unknown, recently published reports of familial cases indicate a possible genetic correlation. Case Presentation: We report 6 cases of familial alopecia composed of mothers and daughters: five with FFA and one with FAPD. We describe clinical, trichoscopy and histological correlation in cases of familial alopecia. Conclusions: These cases of mother and daughter disease association suggest a potential benefit of and role for performing systematic scalp examinations of all first-degree relatives of patients with pattern cicatricial alopecia.
Is There a Link Between Diabetes Mellitus and Cancer?
Authors: Hill Alyson
Published: March 2023

The number of new cases of cancer is increasing each year, and rates of diabetes mellitus are also increasing dramatically over time. It is not an unusual occurrence for an individual to have both cancer and diabetes at the same time, given they are both individually common, and that one condition can increase the risk of the other. In this manuscript, we use national-level diabetes (Virtual Diabetes Register) and cancer (New Zealand Cancer Registry) data on nearly five million individuals over 44 million person-years of follow-up to examine the occurrence of cancer amongst a national prevalent cohort of patients with diabetes. We completed this analysis separately by cancer for the 24 most commonly diagnosed cancers in Aotearoa New Zealand, and then compared the occurrence of cancer among those with diabetes to those without diabetes. We found that the rate of cancer was highest amongst those with diabetes for 21 of the 24 most common cancers diagnosed over our study period, with excess risk among those with diabetes ranging between 11% (non-Hodgkin's lymphoma) and 236% (liver cancer). The cancers with the greatest difference in incidence between those with diabetes and those without diabetes tended to be within the endocrine or gastrointestinal system, and/or had a strong relationship with obesity. However, in an absolute sense, due to the volume of breast, colorectal and lung cancers, prevention of the more modest excess cancer risk among those with diabetes (16%, 22% and 48%, respectively) would lead to a substantial overall reduction in the total burden of cancer in the population. Our findings reinforce the fact that diabetes prevention activities are also cancer prevention activities, and must therefore be prioritised and resourced in tandem.
Non-Pharmacological Interventions to Improve Physical Function in Patients with End-Stage Renal Disease: A Network Meta-Analysis
Authors: Zhao Qian , He Yapeng , Wu Ning , Wang Lili , Dai Jinghua , Wang Juzi , Ma Ji
Published: March 2023

Introduction: Chronic kidney disease is estimated to become the fifth leading cause of death globally by 2040. Due to the high incidence of fatigue in patients with end-stage renal disease without reliable pharmacological treatments, more and more studies on non-pharmacological interventions to improve physical function appear; which might be the best approach remains unknown. This study aimed to compare and rank the efficacy of all known non-pharmacological interventions on improving physical function from multiple outcomes for adults with end-stage renal disease. Methods: This systematic review and network meta-analysis included searches of PubMed, Embase, CINAHL, and Cochrane Library from inception to September 1, 2022, for randomized controlled trials of non-pharmacological interventions to improve physical function in adults with end-stage renal disease. Literature screening, data extraction, and quality appraisal were performed systematically by two independent reviewers. The frequentist random-effect network meta-analysis was adopted to pool the evidence from five outcomes, namely, 6-min walk test, handgrip strength, knee extension strength, physical component summary, and mental component summary, respectively. Results: A total of 1,921 citations were identified by this search, of which 44 eligible trials enrolled 2,250 participants, and 16 interventions were identified. All subsequent figures refer to comparisons with usual care. For increasing walking distance, the combined resistance and aerobic exercise with virtual reality or music were the most effective interventions, with a mean difference plus 95% confidence interval of 90.69 (8.92–172.46) and 92.59 (23.13–162.06), respectively. Resistance exercise with blood flow restriction (8.13, 0.09–16.17) was the best treatment to improve handgrip strength. Combined resistance and aerobic exercise (11.93, 3.63–20.29) and whole-body vibration (6.46, 1.71–11.20) were associated with improving knee extension strength. For life quality, all treatment effects did not show statistically significant differences. Conclusions: It was found via network meta-analysis that combined resistance and aerobic exercise is the most effective intervention. Besides, if virtual reality or music is added to the training, there will be better results. Resistance exercise with blood flow restriction and whole-body vibration might be good alternative treatments for improving muscle strength. None of the interventions improved quality of life, suggesting a need for alternative interventions in this regard. The results of this study contribute evidence-based data to decision-making.
Algumas observações sobre o actinote morio oberthuer, 1917. (Lep. Heliconiidae, Acraeinae)
Authors: D'Almeida R. Ferreira
Published: March 2023

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Mobil Alışverişlerde Algılanan Hizmet Kalitesinin Müşteri Memnuniyeti, Tekrar Satın Alma Niyeti ve Tavsiye Etme Niyeti Üzerindeki Etkisinin İncelenmesi
Authors: BORA SEMİZ Buket
Published: March 2023

Bu çalışmanın amacı, mobil alışverişlerde hizmet kalitesinin müşteri memnuniyeti, müşteri memnuniyetinin de tekrar satın alma niyeti ve tavsiye etme niyeti üzerindeki etkisinin incelenmesidir. Bu bağlamda 18.05.2022- 25.06.2022 tarihleri arasında Google Formlar aracılığıyla çeşitli sosyal medya kanallarında linkler dağıtılarak daha önce mobil alışveriş yapmış 18 yaş ve üzeri 503 katılımcıdan kolayda örnekleme yöntemiyle veri toplanmıştır. SPSS ve AMOS paket programları aracılığıyla analizler gerçekleştirilmiştir. Araştırma sonucuna göre, katılımcılar ayda birkaç kez mobil alışveriş yapmakta ve en çok Trendyol uygulamasını kullanmaktadır. Yapısal eşitlik modellemesi sonucunda da algılanan hizmet kalitesinin algılanan kullanım kolaylığı, güven ve müşteri hizmetleri boyutlarının müşteri memnuniyeti üzerinde etkisinin olduğu, müşteri memnuniyetinin ise tavsiye etme niyeti ve tekrar satın alma niyeti üzerinde etkisi olduğu görülmüştür.
Güvenlikçi Devletin Güçlenmesi Örneği: Türkiye’de 1980 Sonrasında Askeri İdarenin Büyümesi
Authors: ERKEN Baki
Published: March 2023

Bu makale, Türkiye’de 1980 sonrasında ordu ve daha geniş kapsamda askeri idare konusunda güvenlikçi devlet anlayışı bakış açısı ile kurumsal boyutta bir incelemeyi kapsamaktadır. 20. yüzyılda Batı’da güvenlikçi devletin güçlenmesi söz konusudur. Güvenlikçi devletin en önemli yansıması kurumsal boyutta orduda görülmektedir. Türkiye’de 1980 sonrasında askeri idarenin büyümesi güvenlikçi devletin güçlenmesinin önemli bir örneğidir. Bu makale, güvenlikçi devlet anlayışı doğrultusunda Türkiye’de 1980 sonrasında askeri idarenin büyüdüğünü göstermek ve büyümenin nasıl gerçekleştiğini açıklamak amacındadır. Türkiye’de 1980 sonrasında askeri idarenin kurumsal büyümesi üç boyutta ya da alanda gerçekleşmiştir: askeri kurumlar, ordu yapılanması ve askeri personel. Askeri kurumlar çoğalırken ordu yapılanması büyümüş ve askeri personelin statüsü güçlenmiştir. Sonuçta, güçlü devlet geleneği devam etmiş ve sivil siyasal iktidarın gücü ordu karşısında azalmıştır. Yöntemler olarak, makalede kaynak taraması ve veri analizi kullanılmıştır.