bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of crucial genes and pathways associated with prostate cancer in multiple databases
Authors: Guo Hanxu , Zhang Zhichao , Wang Yuhang , Xue Sheng 
Published: June 2021

Objective Prostate cancer (PCa) is a malignant neoplasm of the urinary system. This study aimed to use bioinformatics to screen for core genes and biological pathways related to PCa. Methods The GSE5957 gene expression profiles were obtained from the Gene Expression Omnibus (GEO) database to identify differentially expressed genes (DEGs). Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses of the DEGs were constructed by R language. Furthermore, protein–protein interaction (PPI) networks were generated to predict core genes. The expression levels of core genes were examined in the Tumor Immune Estimation Resource (TIMER) and Oncomine databases. The cBioPortal tool was used to study the co-expression and prognostic factors of the core genes. Finally, the core genes of signaling pathways were determined using gene set enrichment analysis (GSEA). Results Overall, 874 DEGs were identified. Hierarchical clustering analysis revealed that these 24 core genes have significant association with carcinogenesis and development . LONRF1, CDK1, RPS18, GNB2L1 ( RACK1), RPL30, and SEC61A1 directly related to the recurrence and prognosis of PCa. Conclusions This study identified the core genes and pathways in PCa and provides candidate targets for diagnosis, prognosis, and treatment.
Retrospective study of the clinicopathological characteristics and prognosis of elderly patients with oropharyngeal squamous cell carcinoma
Authors: Li Yingbang , Jiang Bifeng , Huang Mingdi , Wang Guangwen , Bai Yunpeng , Huang Wendong 
Published: June 2021

Objective Oropharyngeal squamous cell carcinoma (OPSCC) is a malignant tumor that occurs at the tongue base, soft palate, palatine tonsil, and pharyngeal wall. Few studies of OPSCC have been performed in elderly patients. Methods Patients with human papilloma virus (HPV)-related OPSCC were extracted from the Head and Neck with HPV Status Database of the Surveillance, Epidemiology, and End Results (SEER) database between 2010 and 2016. We identified 355 patients with HPV-positive status, and we retrospectively evaluated elderly (≥65 years) and younger (30–64 years) patient groups to compare the differences. Results Of the 355 patients who were diagnosed with HPV-related OPSCC, 113 constituted the elderly group. Comparing the elderly group with the younger group, the 3-year HPV-positive overall survival (OS) rates were 62.4% and 70.2%, respectively, and the 5-year OS rates were 50.4% and 59.2%, respectively. Cox regression analysis demonstrated that tumor (T) stage and chemotherapy were prognostic factors for OS. Conclusion Elderly patients with OPSCC had different clinicopathological characteristics. T stage and chemotherapy should be priorities when evaluating the OS of elderly patients with OPSCC.
MLN4924 inhibits cell proliferation by targeting the activated neddylation pathway in endometrial carcinoma
Authors: Liu Huanrong , Bei Qiaoli , Luo Xiaoqian 
Published: June 2021

Objective To explore the neddylation pathway, found to be highly activated in various cancers, as a potential therapeutic target in endometrial carcinoma, one of the three most frequent malignant tumours in the female reproductive system. Methods Data from The Cancer Genome Atlas were analysed using online servers. Expression levels of key neddylation genes were validated by reverse-transcription polymerase chain reaction and western blots of tumour and adjacent tissues. Underlying mechanisms and the effects on cell activities of the neddylation pathway-specific inhibitor, MLN4924, were investigated in endometrial cancer cell lines. Results Key neddylation enzymes, ubiquitin conjugating enzyme E2 M ( UBC12), ubiquitin conjugating enzyme E2 F ( UBE2F), ring-box 1 ( RBX1) and ring finger protein 7 ( RBX2), were significantly overexpressed in endometrial carcinoma tissues versus normal tissues, but only UBE2F and RBX2 positively correlated with patient survival. MLN4924 significantly suppressed proliferation and colony formation in EC cells by inducing DNA re-replication, cell cycle arrest and apoptosis. Mechanism study revealed that MLN4924 induced the accumulation of cullin-RING ligase substrates in vitro. Conclusions The neddylation pathway was identified to play an important role in endometrial cancer. The neddylation specific inhibitor, MLN4924, may be a potential therapeutic drug for endometrial carcinoma.
Restless legs-like syndrome as an emergent adverse event of CGRP monoclonal antibodies: A report of two cases
Authors: González-Quintanilla Vicente , Pérez-Pereda Sara , González-Suárez Andrea , Madera Jorge , Toriello María , Pascual Julio 
Published: June 2021

Background One of the advantages of CGRP monoclonal antibodies is their excellent safety and tolerability. However, postmarketing surveillance, is essential to detect potential rare emergent adverse events. Objectives To report two patients who developed restless legs syndrome symptoms after treatment with CGRP antibodies. Methods and results Two women with chronic refractory migraine, with no significant medical antecedents, developed typical restless legs syndrome symptoms 1.5 and 4 months after starting erenumab 140 mg, respectively. In case 1 symptoms resolved when erenumab was stopped for two months but reappeared on galcanezumab. In both patients migraine attacks had dramatically decreased and no iron deficiency was found. Conclusions Even though caution is needed before establishing a causal relationship, these cases suggest that restless legs-like symptoms might be an emergent adverse event of CGRP antibodies, regardless of the mechanism of action. We propose that plastic changes in CGRP sensory fibers, which are very abundant in legs, induced by CGRP monoclonal antibodies could be the reason for restless legs syndrome development.
Comparison of Cellular Responses to TGF-β1 and BMP-2 Between Healthy and Torn Tendons
Authors: Morita Wataru , Snelling Sarah J.B. , Wheway Kim , Watkins Bridget , Appleton Louise , Murphy Richard J. , Carr Andrew J. , Dakin Stephanie G. 
Published: June 2021

Background: Tendons heal by fibrotic repair, increasing the likelihood of reinjury. Animal tendon injury and overuse models have identified transforming growth factor beta (TGF-β) and bone morphogenetic proteins (BMPs) as growth factors actively involved in the development of fibrosis, by mediating extracellular matrix synthesis and cell differentiation. Purpose: To understand how TGF-β and BMPs contribute to fibrotic processes using tendon-derived cells isolated from healthy and diseased human tendons. Study Design: Controlled laboratory study. Methods: Tendon-derived cells were isolated from patients with a chronic rotator cuff tendon tear (large to massive, diseased) and healthy hamstring tendons of patients undergoing anterior cruciate ligament repair. Isolated cells were incubated with TGF-β1 (10 ng/mL) or BMP-2 (100 ng/mL) for 3 days. Gene expression was measured by real-time quantitative polymerase chain reaction. Cell signaling pathway activation was determined by Western blotting. Results: TGF-β1 treatment induced ACAN mRNA expression in both cell types but less in the diseased compared with healthy cells ( P < .05). BMP-2 treatment induced BGN mRNA expression in healthy but not diseased cells ( P < .01). In the diseased cells, TGF-β1 treatment induced increased ACTA2 mRNA expression ( P < .01) and increased small mothers against decapentaplegic (SMAD) signaling ( P < .05) compared with those of healthy cells. Moreover, BMP-2 treatment induced ACTA2 mRNA expression in the diseased cells only ( P < .05). Conclusion: Diseased tendon–derived cells show reduced expression of the proteoglycans aggrecan and biglycan in response to TGF-β1 and BMP-2 treatments. These same treatments induced enhanced fibrotic differentiation and canonical SMAD cell signaling in diseased compared with healthy cells. Clinical Relevance: Findings from this study suggest that diseased tendon–derived cells respond differently than healthy cells in the presence of TGF-β1 and BMP-2. The altered responses of diseased cells may influence fibrotic repair processes during tendon healing.
High Rate of Initially Overlooked Kaplan Fiber Complex Injuries in Patients With Isolated Anterior Cruciate Ligament Injury
Authors: Berthold Daniel P. , Willinger Lukas , LeVasseur Matthew R. , Marrero Daniel E. , Bell Ryan , Muench Lukas N. , Kane Zenon , Imhoff Andreas B. , Herbst Elmar , Cote Mark P. , Arciero Robert A. , Edgar Cory M. 
Published: June 2021

Background: Injuries to the Kaplan fiber complex (KFC) are not routinely assessed for in the anterior cruciate ligament (ACL)-deficient knee during preoperative magnetic resonance imaging (MRI). As injuries to the KFC lead to anterolateral rotatory instability (ALRI) in the ACL-deficient knee, preoperative detection of these injuries on MRI scans may help surgeons to individualize treatment and improve outcomes, as well as to reduce failure rates. Purpose: To retrospectively determine the rate of initially overlooked KFC injuries on routine MRI in knees with isolated primary ACL deficiency. Study Design: Case series; Level of evidence, 4. Methods: Patients who underwent isolated ACL reconstruction between August 2013 and December 2019 were identified. No patient had had Kaplan fiber (KF) injury identified on the initial reading of the MRI scan or at the time of surgery. Preoperative knee MRI scans (minimum 1.5 T) were reviewed and injuries to the proximal and distal KFs were recorded by 3 independent reviewers. KF length and distance to nearby anatomic landmarks (the lateral joint line and the lateral femoral epicondyle) were measured. Additional radiological findings, including bleeding, lateral femoral notch sign, and bone marrow edema (BME), were identified to detect correlations with KFC injury. Results: The intact KFC could reliably be identified by all 3 reviewers (85.9% agreement; Kappa, 0.716). Also, 53% to 56% of the patients with initially diagnosed isolated ACL ruptures showed initially overlooked injuries to the KFC. Injuries to the distal KFs were more frequent (48.1%, 53.8%, and 43.3% by the first, second, and third reviewers, respectively) than injuries to the proximal KFs (35.6%, 47.1%, and 45.2% by the first, second, and third reviewers, respectively). Bleeding in the lateral supracondylar region was associated with KFC injuries ( P = .023). Additionally, there was a positive correlation between distal KF injuries and lateral tibial plateau BME ( P = .035), but no associations were found with the lateral femoral notch sign or other patterns of BME, including pivot-shift BME. Conclusion: KF integrity and injury can be reliably detected on routine knee MRI scans. Also, 53% to 56% of the patients presenting with initially diagnosed isolated ACL ruptures had concomitant injuries to the KFC. This is of clinical relevance, as ACL injuries diagnosed by current routine MRI examination protocols may come with a high number of occult or hidden KFC injuries. As injuries to the KFC contribute to persistent ALRI, which may influence ACL graft failure or reoperation rates, significant improvements in preoperative diagnostic imaging are required to determine the exact injury pattern and to assist in surgical decision making.
Antiphospholipid antibodies and cerebrovascular thrombosis in the pediatric population: Few answers to many questions
Authors: Hasbani Georges El , Taher Ali T , Sunji Nadine , Sciascia Savino , Uthman Imad 
Published: June 2021

Most of the knowledge in pediatric antiphospholipid syndrome (APS) is derived from studies performed on the adult population. As in adults, antiphospholipid antibodies (aPL) can contribute to thrombosis, especially cerebrovascular thrombosis, in neonates and children. Since aPL have the potential to cross the placental barrier, and since the pediatric population is prone to infections, re-testing for their positivity is essential to specify their role in cerebrovascular thrombosis. In this review, we aimed at assessing the prevalence of aPL, criteria or non-criteria, in neonatal and childhood ischemic stroke and sinovenous thrombosis trying to find an association between aPL and cerebrovascular thrombosis in the neonatal and pediatric population. Also, we looked into the effect of aPL and anticoagulants/antiplatelets on the long term neurological outcomes of affected neonates or children. The questions regarding the prevalence of aPL among pediatric patients with cerebrovascular thrombosis, the relationship between the titers of aPL and incidence and recurrence of cerebrovascular events, the predictability of the long term neurological outcomes, and the most optimal anticoagulation plan are still to be answered. However, it is crucial for clinicians to screen neonates and children with cerebrovascular thrombosis for aPL and confirm their presence if positive.
Drug- and patient-related factors are the strongest predictors of endocrine therapy adherence in breast cancer patients
Authors: Haji-Hersi Mariam F , Tilley Sophia , Shelton Caleb A , Lamb Nathan , Kamdem Landry K 
Published: June 2021

Purpose Medication non-adherence to treatment regimens can severely impact the mortality of patients afflicted with breast cancer.The purpose of this study was to identify factors that contribute to non-adherence to endocrine therapy in breast cancer treatment plans. Methods Thirty-two women with a breast cancer diagnosis were surveyed by pharmacists and pharmacy students to identify the patient- related factors (e.g. patient personal beliefs, education level), drug-related factors (e.g. patient drug allergies), socio-economic factors (e.g. patient ability to pay for the medication) and healthcare system factors (e.g. poor patient-healthcare provider relationship) that may impact non-adherence to endocrine therapy in breast cancer treatment plans. Medication adherence rates were measured using the Medication Adherence Rating Scale (MARS-8) system. Associations between adherence rate scores and clinical variables (e.g. age, tobacco use, alcohol consumption, cost of treatment, education level, personal beliefs, drug allergies, patient/provider relationship, adverse events) were carried out using Spearman Correlation, T-Test, Mann-Whitney U Test, and X2 tests. A p value of ≤ 0.05 was considered statistically significant. Results Our study found that 59% of survey respondents were non-adherent to their endocrine therapy in breast cancer treatment plans. Drug allergies ( p = 0.000069), patient ability to pay ( p = 0.005), poor personal beliefs about the prescribed therapy (p = 0.009), low education level ( p = 0.025), adverse drug events ( p = 0.026), and poor patient-provider relationship ( p = 0.05) were found to play a role in patient non-adherence to treatment. Conclusions Our study found that drug- (e.g. allergies), socio-economic (e.g. patient ability to pay), and patient-related factors (e.g. personal beliefs) are the strongest predictors of adherence among breast cancer patients undergoing endocrine therapy. These findings support the need for a better relationship between breast cancer patients and their healthcare providers, including drug experts such as pharmacists.
Clinically Meaningful Improvements in Early Morning and Late Afternoon/Evening Functional Impairment in Children with ADHD Treated with Delayed-Release and Extended-Release Methylphenidate
Authors: Wilens Timothy E. , Faraone Stephen V. , Hammerness Paul G. , Pliszka Steven R. , Uchida Cassandra L. , DeSousa Norberto J. , Sallee Floyd R. , Incledon Bev , Newcorn Jeffrey H. 
Published: June 2021

Objective: The Before School Functioning Questionnaire and Parent Rating of Evening and Morning Behavior–Revised assess early morning (BSFQ, PREMB-R AM subscale) and late afternoon/evening (PREMB-R PM subscale) functional impairment in children with ADHD. Clinically meaningful improvements were identified and applied to a trial of delayed-release and extended-release methylphenidate (DR/ER-MPH) in children with ADHD (NCT02520388) to determine if the statistically-determined improvements in functional impairment were also clinically meaningful. Method: Clinically meaningful improvements in BSFQ/PREMB-R were established post hoc by receiver operating characteristics curves, using anchors of Clinical Global Impression–Improvement (CGI-I) = 1 and CGI-I ≤ 2. Percentages of participants achieving these thresholds were calculated. Results: Thresholds for CGI-I = 1/CGI-I ≤ 2, respectively, were 27/20 (BSFQ), 5/3 (PREMB-R AM), and 9/5 (PREMB-R PM)-point decreases. More children achieved clinically meaningful improvements with DR/ER-MPH versus placebo (all p < .05). Conclusion: DR/ER-MPH increased proportions of children achieving clinically meaningful improvements in BSFQ and PREMB-R.
Follicular lymphoma of the ocular adnexa: Clinicopathological findings with flow cytometry analysis of eight cases
Authors: Mitamura Mizuho , Kase Satoru , Suzuki Yasuo , Sakaguchi Takatoshi , Suimon Yuka , Dong Yoko , Hatanaka Kanako C , Sinohara Toshiya , Kase Manabu , Ishida Susumu 
Published: June 2021

Purpose: Flow cytometry (FCM) is used to evaluate cell surface markers of various leukocyte populations quantitatively. However, little is known about the usefulness of FCM in follicular lymphoma (FL) of the ocular adnexa. The aim of this study was to evaluate the clinicopathological features and FCM results in ocular adnexal FL. Materials: This is a retrospective multicenter case study on clinical and immunohistochemical features. All tumors, surgically excised, were diagnosed based on histopathology, immunoglobulin heavy chain gene rearrangement, and FCM. The percentages (%) of B-cell markers, T-cell markers, a natural killer cell marker, and cell surface kappa/lambda measured by FCM analysis in tumor tissues were searched based on medical records. Results: This study enrolled nine tumors in eight FL patients (three men and five women). The median age at the time of initial presentation was 74 years. All the tumors surgically excised histologically exhibited cluster of differentiation (CD)10, CD20, and BCL2-positive cells. At the time of ophthalmic diagnosis, lymphomas were already disseminated throughout the body in five cases. FCM demonstrated high percentage of B-cell markers including CD10, CD19, CD20, and CD23 in all nine tumors. CD10 population was 73.5% ± 11.9% in seven out of nine tumors, while that in the other two tumors was particularly low being 11.7% ± 1.13%, which showed the relatively high T-cell lineages compared to the other seven tumors. Conclusion: For ophthalmologists involving managements of ocular adnexal tumors, FCM can provide useful information for complementing the diagnosis and understanding pathophysiology of FL.
Impact of Andrographolide and Melatonin Combinatorial Drug Therapy on Metastatic Colon Cancer Cells and Organoids
Authors: Sharda Neha , Ikuse Tamaki , Hill Elizabeth , Garcia Sonia , Czinn Steven J , Bafford Andrea , Blanchard Thomas G , Banerjee Aditi 
Published: June 2021

Background: The death rate (the number of deaths per 100 000 people per year) of colorectal cancer (CRC) has been dropping since 1980 due to increased screening, lifestyle-related risk factors, and improved treatment options; however, CRC is the third leading cause of cancer-related deaths in men and women in the United States. Therefore, successful therapy for CRC is an unmet clinical need. This study aimed to investigate the impacts of andrographolide (AGP) and melatonin (MLT) on CRC and the underlying mechanism. Methods: To investigate AGP and MLT anticancer effects, a series of metastatic colon cancer cell lines (T84, Colo 205, HT-29, and DLD-1) were selected. In addition, a metastatic patient-derived organoid model (PDOD) was used to monitor the anticancer effects of AGP and MLT. A series of bioassays including 3D organoid cell culture, MTT, colony formation, western blotting, immunofluorescence, and quantitative polymerase chain reaction (qPCR) were performed. Results: The dual therapy significantly promotes CRC cell death, as compared with the normal cells. It also limits CRC colony formation and disrupts the PDOD membrane integrity along with decreased Ki-67 expression. A significantly higher cleaved caspase-3 and the endoplasmic reticulum (ER) stress proteins, IRE-1 and ATF-6 expression, by 48 hours were found. This combinatorial treatment increased reactive oxygen species (ROS) levels. Apoptosis signaling molecules BAX, XBP-1, and CHOP were significantly increased as determined by qPCR. Conclusions: These findings indicated that AGP and MLT associated ER stress-mediated apoptotic metastatic colorectal cancer (mCRC) cell death through the IRE-1/XBP-1/CHOP signaling pathway. This novel combination could be a potential therapeutic strategy for mCRC cells.
Mental health of people with multiple sclerosis during the COVID-19 outbreak: A prospective cohort and cross-sectional case–control study of the UK MS Register
Authors: Garjani Afagh , Hunter Rachael , Law Graham R , Middleton Rodden M , Tuite-Dalton Katherine A , Dobson Ruth , Ford David V , Hughes Stella , Pearson Owen R , Rog David , Tallantyre Emma C , Nicholas Richard , Morriss Richard , Evangelou Nikos , das Nair Roshan 
Published: June 2021

Background: People with MS (pwMS) have had higher rates of anxiety and depression than the general population before the COVID-19 pandemic, placing them at higher risk of experiencing poor psychological wellbeing during the pandemic. Objective: To assess mental health and its social/lifestyle determinants in pwMS during the first wave of the outbreak in the United Kingdom. Methods: This is a community-based, prospective longitudinal cohort and cross-sectional case–control online questionnaire study. It includes 2010 pwMS from the UK MS Register and 380 people without MS. Results: The Hospital Anxiety and Depression Scale scores of pwMS for anxiety and depression during the outbreak did not change from the previous year. PwMS were more likely to have anxiety (using General Anxiety Disorder-7) and/or depression (using Patient Health Questionnaire-9) than controls during the outbreak (OR: 2.14, 95% CI: 1.58–2.91). PwMS felt lonelier (OR: 1.37, 95% CI: 1.04–1.80) reported worse social support (OR: 1.90, 95% CI: 1.18–3.07) and reported worsened exercise habits (OR: 1.65, 95% CI: 1.18–2.32) during the outbreak than controls. Conclusion: Early in the pandemic, pwMS remained at higher risk of experiencing anxiety and depression than the general population. It is important that multidisciplinary teams improve their support for the wellbeing of pwMS, who are vulnerable to the negative effects of the pandemic on their lifestyle and social support.