bluuebunny/crossref_metadata_2025_split huggingface dataset:
JAZF1–SUZ12 endometrial stromal sarcoma forming subserosal masses with extraordinary uptake of fluorodeoxyglucose on positron emission tomography: a case report
Authors: Fujiishi Koto , Nagata Shigenori , Kano Rieko , Kubo Chiaki , Shirayanagi Maasa , Ozaki Megumi , Yamamoto Takashi , Nakanishi Katsuyuki , Kamiura Shoji , Nakatsuka Shin-ichi 
Published: October 2019

AbstractBackgroundLow-grade endometrial stromal sarcoma (ESS) is rare mesenchymal neoplasm, recently specified as harboringJAZF1–SUZ12rearrangement. TypicalJAZF1–SUZ12ESS is slow growing, in which high uptake of fluorodeoxyglucose (FDG) on positron emission tomography (PET) and subserosal masses are quite unusual.Case presentationA 69-year-old Japanese woman complained of urinary incontinence. Pelvic magnetic resonance imaging showed uterine lesions composed of (1) a 9 × 8 × 7-cm mass protruding from the right-anterior wall, (2) a 4.5-cm mass attached to the right-posterior wall, and (3) a 6.5-cm intramural mass in the fundus. FDG-PET demonstrated maximum standardized uptake value of 13.28 confined to the two subserosal masses (1 & 2) in contrast to no uptake of the intramural mass (3). She was diagnosed with a high-grade uterine sarcoma concomitant with leiomyomas and underwent total hysterectomy with bilateral salpingo-oophorectomy and pelvic lymphadenectomy. The removed uterus had three tumors—two in the right-anterior and right-posterior subserosa, respectively, and the remaining in the fundal myometrium. Microscopically, the three tumors shared morphologic features characterized by neoplastic cells similar to proliferative-phase endometrial stromal cells, in which neither round-cell component, pleomorphism, nor high mitotic activity was recognized. Nuclear cyclin D1 immunostaining was identified 50% of neoplastic cells in the two subserosal tumors (1 &2) whereas < 1% positive cells in the intramural component (3). Reverse transcriptase-polymerase chain reaction showed the same-sized electrophoretic bands indicatingJAZF1–SUZ12gene fusion shared by the three uterine tumors and a focal tumor extension into the extrauterine vein. The patient is alive without evidence of recurrence at 14 months after surgery.ConclusionsPathologists and clinicians should not exclude the possibility ofJAZF1–SUZ12ESS even when uterine subserosal masses demonstrate extraordinary FDG uptake on PET. Molecular analysis is helpful for diagnostic confirmation ofJAZF1–SUZ12ESS with a complex growth pattern.
The use or generation of biomedical data and existing medicines to discover and establish new treatments for patients with rare diseases – recommendations of the IRDiRC Data Mining and Repurposing Task Force
Authors:   on behalf of the IRDiRC Data Mining and Repurposing Task Force, Southall Noel T , Natarajan Madhusudan , Lau Lilian Pek Lian , Jonker Anneliene Hechtelt , Deprez Benoît , Guilliams Tim , Hunter Lawrence , Rademaker Carin MA , Hivert Virginie , Ardigò Diego 
Published: October 2019

Abstract
The number of available therapies for rare diseases remains low, as fewer than 6% of rare diseases have an approved treatment option. The International Rare Diseases Research Consortium (IRDiRC) set up the multi-stakeholder Data Mining and Repurposing (DMR) Task Force to examine the potential of applying biomedical data mining strategies to identify new opportunities to use existing pharmaceutical compounds in new ways and to accelerate the pace of drug development for rare disease patients. In reviewing past successes of data mining for drug repurposing, and planning for future biomedical research capacity, the DMR Task Force identified four strategic infrastructure investment areas to focus on in order to accelerate rare disease research productivity and drug development: (1) improving the capture and sharing of self-reported patient data, (2) better integration of existing research data, (3) increasing experimental testing capacity, and (4) sharing of rare disease research and development expertise. Additionally, the DMR Task Force also recommended a number of strategies to increase data mining and repurposing opportunities for rare diseases research as well as the development of individualized and precision medicine strategies.
LncRNA H19 over-expression inhibited Th17 cell differentiation to relieve endometriosis through miR-342-3p/IER3 pathway
Authors: Liu Zheying , Liu Liya , Zhong Yun , Cai Mingbo , Gao Junbi , Tan Chaoyue , Han Xiaoxiao , Guo Ruixia , Han Liping 
Published: October 2019

Abstract

Objective
To investigate the mechanism of LncRNA H19 in Th17 cell differentiation and endometrial stromal cells (ESCs) proliferation in endometriosis (EMS).

Methods
LncRNA H19, miR-342-3p and IER3 expressions were detected by qRT-PCR and western blot. The percentage of Th17 cells/CD4+ T cells was detected by flow cytometry. IL-17 level was measured by ELISA. The interaction of miR-342-3p and IER3 was confirmed by Luciferase reporter assay.

Results
LncRNA H19 and IER3 expressions were down-regulated in mononuclear cells from peritoneal fluid (PFMCs) of patients with EMS or under Th17 differentiation conditions, whereas miR-342-3p expression was up-regulated and the percentage of Th17 cells was increased in PFMCs of patients with EMS or under Th17 differentiation conditions. Over-expression of LncRNA H19 decreased IL-17 level and the percentage of Th17 cells/CD4+ T cells. Besides, we confirmed that miR-342-3p could target to IER3 and negatively regulate IER3 expression. LncRNA H19 over-expression suppressed Th17 differentiation and ESC proliferation through regulating miR-342-3p/IER3. In vivo experiments showed LncRNA H19 over-expression suppressed the growth of Th17 cell differentiation-induced endometriosis-like lesions.

Conclusion
LncRNA H19 was down-regulated in PFMC of patients with EMS or under Th17 polarizing conditions, and LncRNA H19 over-expression suppressed Th17 cell differentiation and ESCs proliferation through miR-342-3p/IER3 pathway.
Neurosurgical applications of MRI guided laser interstitial thermal therapy (LITT)
Authors: Salem Usama , Kumar Vinodh A. , Madewell John E. , Schomer Donald F. , de Almeida Bastos Dhiego Chaves , Zinn Pascal O. , Weinberg Jeffrey S. , Rao Ganesh , Prabhu Sujit S. , Colen Rivka R. 
Published: October 2019

Abstract
MRI-guided laser interstitial thermal therapy (LITT) is the selective ablation of a lesion or a tissue using heat emitted from a laser device. LITT is considered a less invasive technique compared to open surgery that provides a nonsurgical solution for patients who cannot tolerate surgery. Although laser ablation has been used to treat brain lesions for decades, recent advances in MRI have improved lesion targeting and enabled real-time accurate monitoring of the thermal ablation process. These advances have led to a plethora of research involving the technique, safety, and potential applications of LITT.
LITT is a minimally invasive treatment modality that shows promising results and is associated with decreased morbidity. It has various applications, such as treatment of glioma, brain metastases, radiation necrosis, and epilepsy. It can provide a safer alternative treatment option for patients in whom the lesion is not accessible by surgery, who are not surgical candidates, or in whom other standard treatment options have failed. Our aim is to review the current literature on LITT and provide a descriptive review of the technique, imaging findings, and clinical applications for neurosurgery.
Resveratrol modulates the Akt/GSK-3β signaling pathway in a middle cerebral artery occlusion animal model
Authors: Park Dong-Ju , Kang Ju-Bin , Shah Fawad-Ali , Koh Phil-Ok 
Published: October 2019

Abstract
Cerebral ischemia is a major cause of neurodegenerative disease. It induces neuronal vulnerability and susceptibility, and leads to neuronal cell death. Resveratrol is a polyphenolic compound that acts as an anti-oxidant. It exerts a neuroprotective effect against focal cerebral ischemic injury. Akt signaling pathway is accepted as a representative cell survival pathway, including proliferation, growth, and glycogen synthesis. This study investigated whether resveratrol regulates Akt/glycogen synthase kinase-3β (GSK-3β) pathway in a middle cerebral artery occlusion (MCAO)-induced ischemic brain injury. Adult male rats were intraperitoneally injected with vehicle or resveratrol (30 mg/kg) and cerebral cortices were isolated 24 h after MCAO. Neurological behavior test, corner test, brain edema measurment, and 2,3,5-triphenyltetrazolium chloride staining were performed to elucidate the neuroprotective effects of resveratrol. Phospho-Akt and phospho-GSK-3β expression levels were measured using Western blot analysis. MCAO injury led to severe neurobehavioral deficit, infraction, and histopathological changes in cerebral cortex. However, resveratrol treatment alleviated these changes caused by MCAO injury. Moreover, MCAO injury induced decreases in phospho-Akt and phospho-GSK-3β protein levels, whereas resveratrol attenuated these decreases. Phosphorylations of Akt and GSK-3β act as a critical role for the suppression of apoptotic cell death. Thus, our finding suggests that resveratrol attenuates neuronal cell death in MCAO-induced cerebral ischemia and Akt/GSK-3β signaling pathway contributes to the neuroprotective effect of resveratrol.
Prognostic value of trafficking of regulatory T cells to tumors in head and neck cancer patients.
Authors: Chang Hyun , Hong Hyun Jun , Kim Yongho 
Published: October 2019

104 Background: The prognostic value of regulatory T cells (Tregs) in head and neck squamous cell carcinoma (HNSCC) remains unknown. We analyzed the prognostic effect of Tregs in HNSCC with immune activity scores, which reflect the activity status of the seven-step cancer-immunity cycle. Methods: We correlated the 23 immune activity scores and clinicopathologic features of The Cancer Genome Atlas (TCGA) HNSCC using multivariate Cox regression analyses and Kaplan-Meier survival curves. The processed data of immune activity scores were obtained from TIP online tool and the clinicopathologic data were downloaded from TCGA HNSCC database. Results: Immune activity scores of “trafficking of Tregs to tumors” was significantly associated with overall survival (OS) and progression-free survival (PFS). Low activity scores of “trafficking of Tregs to tumors” resulted in shorter OS and PFS. In multivariate analysis, low scores predicted poor OS (adjusted HR = 1.87, 95% CI 1.34-2.60 ; P < 0.001) and were related with unfavorable PFS (adjusted HR = 2.04, 95% CI 1.45-2.86 ; P < 0.001). Conclusions: Immune activity scores of “trafficking of Tregs to tumors” was independent significant prognostic factor in HNSCC. Therefore, assessment of immune activity scores may be useful tools for predicting prognosis in these patients.
Deep learning analysis for automatic lung nodule detection.
Authors: Liu Xiaohua 
Published: October 2019

27 Background: The prevalence of lung cancer has been increased markedly in worldwide range with growing clinical significance, the quantitative and qualitative analysis on lung nodules has proven to be important for the early-detection of lung cancer as well as its treatment in clinical practice. However, lung lesion screening performed by radiologists can be very time-consuming and its accuracy varies depending on doctor’s individual experiences. In this study, we aim to build up a robust CAD system that automatically detects the lesion locations and quantitatively characterizes the detected lesions on CT images. Methods: Specifically, we employed the deep learning analysis for lesion detection in patients and performed image processing techniques to generate quantitative morphology features for assisting lesion diagnosis . The data collected includes 3956 lung CT series (slice thickness≤3mm) with multiple lung nodules from 15 Class-A hospitals in China , 1155 lung CT scan from Luna16 dataset as well as CT scans from Kaggle dataset (Data Science Bowl 2017). Lung nodule annotation was then performed by two experienced radiologists and further assessed by four senior associate chief physicians. The obtained CT images were randomly selected and split to construct training, validation and test dataset. After preprocessing, a pre-trained ResNet18 framework is transferred to develop a robust detection system to detect the possible lung lesion locations with corresponding probabilities. Results: The resulting detection system yields FROC of 0.4663, recall of 82.46%, precision of 36.06% for 5~30mm nodules. Each detected lesion was labeled by its bounding box and was then analyzed through image processing algorithm to generate diagnostic assisting features, including longest diameter, shortest diameter, volume, largest cross section area as well as its density type (calcify, solid, partial solid, and ground-glass opacity). Conclusions: The proposed CAD system offers a fast and convenient approach for assisting the diagnosis of lung nodule pathologies, and it is beneficial to relate our research to the current framework of lung cancer diagnosis.
Tyrosine aminoacyl-tRNA synthetase sensitizes breast cancer to chemotherapy through a necroptosis-mediated mechanism.
Authors: Ryu Han Suk 
Published: October 2019

40 Background: A complete response to chemotherapy for most cancer patients is, and there are many complications caused by this toxic therapy. Therefore, we sought to determine chemotherapy responses in breast cancer at the proteome level. Methods: Candidate proteins were filtered out by the proteomic-based multiple machine-learning algorithms. Results: The MS analysis of FFPE set yielded 6,069 protein groups. The filtered dataset resulted in 539 proteins with differential abundances. We searched for biological process in the Gene Ontology (GO) enrichment analysis in each proteomic cluster. Several immune responses process, apoptotic process, DNA replication process and aminoacylation for protein translation process primarily were represented in group with complete remission. On the other hand, cell adhesion process, cytoskeleton organization process, vesicle organization process and Golgi organization process represented in breast cancer which showed poor responses to the therapy. The machine learning approaches demonstrated the highest AUC value, 0.978 (sensitivity 1.0 and specificity 0.714) with a combination of 11 proteins. Among them the finally selected tyrosine aminoacyl-tRNA synthetase (YARS) showed AUC (AUC = 0.749) in the subsequent steps of verification using immunohistochemistry in 123 patient cohorts. We identified the predictive relevance of YARS. YARS induced tumor necroptosis was greatly enhanced when it was combined synergistically with a combination of SMAC mimetics and a BCL2 inhibitor. Conclusions: This suggested that YARS expression could serve as a new therapeutic target for improving the clinical benefits of chemotherapy.
Access to diagnostics and treatment of neuroendocrine tumors (NETs): The difference between patient perception and reality.
Authors: Leyden Simone , Kolarova Teodora , Bouvier Catherine , Caplin Martyn E. , Conroy Siobhan , Davies Philippa , Dureja Sugandha , Falconi Massimo , Ferolla Piero , Fisher George A. , Goldstein Grace , Hicks Rodney J. , Lawrence Benjamin James , Majima Yoshiyuki , Metz David C. , O'Toole Dermot , Ruszniewski Philippe B. , Wiedenmann Bertram , Hollander Ron ,   International Neuroendocrine Cancer Alliance
Published: October 2019

6 Background: The aim of this global patient survey was to better understand the needs and expectations of patients with NETs regarding access to diagnostic tools and treatment. Methods: In 2017, an online, questionnaire survey of NET patients/family members, patient advocates and healthcare professionals (HCPs) was conducted. Results: In total, 443 participants from 26 countries responded: 338 patients/families; 35 advocates; 70 HCPs. Following NET diagnosis, many patients use patient association (69%) and HCP (48%) websites to fulfill their informational needs. Patients overestimated the availability of key diagnostic tools and treatments compared to HCPs: Gallium-68-Dotatate PET/CT scan was believed available by 28% of patients vs. 14% of HCPs; fluorodeoxyglucose PET by 77% of patients vs. 64% of HCPs; peptide receptor radionuclide therapy by 58% of patients vs. 23% of HCPs; genetic test/precision medicine by 75% of patients vs. 71% of HCPs; and transplantation by 86% of patients vs. 55% of HCPs. Reasons reported by patients and advocates for unavailability of treatment were: not provided by healthcare system (28% & 67%, respectively); non-referral (19% & 33%, respectively), unable to afford treatment (18% & 57%, respectively); treatment not covered by insurance (17% & 24%, respectively); distance to treatment centre (15% & 48%, respectively). Almost a third (30%) of patients had to travel more than 300 km/186 miles for treatment or consultation with a NET specialist, while 34% of patients did not have access to an MDT and those that did may be in contact with them less than once per year (14%). In contrast, advocates and HCPs believe there is wider availability of MDTs (94% and 70%, respectively). Conclusions: Patients are increasingly well-educated about NETs and often travel considerable distances to obtain specialist treatment. However, there remains considerable disparity in what patients feel is available to them in terms of the latest tools and treatments, compared to what is there in reality. This significant difference in perception needs to be managed delicately by both advocates and healthcare professionals.
Randomized phase II clinical trial of pioglitazone plus chemotherapy versus chemotherapy alone in patients with metastatic breast cancer.
Authors: Moghareabed Reza , Hemati Simin , Akhavan Ali , Emami Hamid , Farghadani Maryam , Roayaei Mahnaz , Tavajoh Saeideh , Feizi Awat 
Published: October 2019

83 Background: Breast carcinoma is the second cause of mortality between female cancers and metastasis is the main contributing factor to the mortality in patients with breast cancer. Optimal management for visceral metastatic breast cancer (MBC) remains unknown. In this study we aimed to assess if adding pioglitazone to chemotherapy regimen can improve response in patients with MBC. Methods: This double-blind randomized clinical trial enrolled women 18 years or older with visceral MBC either previously treated with adjuvant therapy or currently are undergoing different lines of endocrine and chemotherapy regimens. The main objective of this study is to compare treatment efficacy in patients with visceral MBC taking chemotherapy plus Pioglitazone (n = 30) versus chemotherapy in addition to placebo (n = 30) over three months. The efficacy evaluated by change in radiologic response defined by the proportion of patients with stable or partial/complete radiologic response to those experienced disease progression based on Revised Recist Guideline ver (1.1). Results: Combination of pioglitazone and chemotherapy led to higher complete radiologic response (7.4% vs.0%) stable disease status (66·7% vs. 53·6%) and lower progression (22·2% vs. 35·7%) rates, however the differences were not statistically significant (P = 0.24). Clinical benefit rate (CBR, proportion of patients with complete response, partial response, or stable disease) was 77.8% in pioglitazone group vs. 64.3% in control group (p = 0.27). Subgroup analysis revealed higher efficacy but not statistically significant among diabetic woman, who had hormone-receptor–positive tumor. Furthermore, patients treated with Taxan +/-Carboplatin agents had significantly higher stable disease status, lower progression rate and higher complete response rate than the placebo group (P = 0·03). Conclusions: This is the first reported randomized clinical trial on the efficacy of pioglitazone in patients with visceral MBC which demonstrated safety and improvement of response in the subgroup of Taxan / Carboplatin chemotherapy regimen. These findings are in agreement with previous results of in vitro preclinical studies. Clinical trial information: IRCT20180124038493N1.
PD-1 blockade in neoadjuvant setting of DNA mismatch repair-deficient/microsatellite instability-high colorectal cancer.
Authors: Liu Dingxin Cancer , Li Dandan , Jiang Wu , PAN Zhizhong , Zhang Xiaoshi , Ding Peirong 
Published: October 2019

84 Background: Although PD-1 blockade has significantly improved the survival of metastatic colorectal cancer with DNA Mismatch Repair-Deficient/Microsatellite Instability-High (MSI-H), the data on neoadjuvant setting is limited. Methods: In this retrospective study, we enrolled eight patients with advanced MSI-H colorectal cancer from three hospitals. four patients are locally advanced and four are metastatic. All the patients received at least two doses of PD-1 antibody with or without chemotherapy as neoadjuvant therapy. The aim of the present study was to evaluate the short‐term efficacy and toxicities of this strategy. Results: Neoadjuvant PD-1 Blockade is well tolerated with a few immune-related side-effect profiles. All the enrolled patients had a major response in imaging and/or pathological evaluation. Five of the seven resected patients were evaluated as pathological complete response. One patient without surgery has a cCR tumor response. For the patients with radical surgery, there is no surgery-related complication observed. Conclusions: Neoadjuvant PD-1 blockade induced tumor regression with a major clinical and pathological response in advanced dMMR/MSI-H colorectal cancer. Further studies are required to evaluate the long-term effect of this strategy.
A Case of Hashimoto’s Thyroiditis with Multiple Drug Resistance and High Expression of Efflux Transporters
Authors: Yoshida Tomohiko , Nakayama Akitoshi , Tamura Ai , Higuchi Seiichiro , Sakuma Ikki , Nagano Hidekazu , Felizola Saulo Ja , Hashimoto Naoko , Takemoto Minoru , Tatsuno Ichiro , Koide Hisashi , Yokote Koutaro , Tanaka Tomoaki 
Published: October 2019

Abstract

Context
Hashimoto’s thyroiditis is the most common cause of hypothyroidism. Patients usually respond well to oral synthetic thyroxine (levothyroxine); however, for unknown reasons some individuals present with treatment-resistant Hashimoto thyroiditis. In cases of cancer and certain infectious diseases, the ATP binding cassette (ABC) transporters have been implicated in multidrug resistance, and we hypothesized and investigated a role of ABC transporters in drug-resistant Hashimoto’s thyroiditis.

Case Description
The patient whose case we report had a history of Hashimoto’s thyroiditis, immune thrombocytopenia, and refractory hypertension, with varying treatment resistance to the oral medications prescribed for each condition. In order to establish or exclude a genetic basis for her illness, we examined the patient’s gene expression profiles using peripheral blood leukocytes, and found that ABCG2/BCRPexpression was significantly high compared with healthy volunteers. Also, the increased daunomycin efflux capacity of our patient’s lymphocytes was successfully inhibited by fumitremorgin C, a specific ABCG2/BCRP inhibitor, and the patient’s level of thyroid-stimulating hormone increased by 248.6% after administration of intact levothyroxine tablets but decreased by 45.1% when tablets were crushed. Her average blood pressure decreased from 166.3/108.5 mmHg to 125.9/78.8 mmHg when switching from intact to crushed losartan tablets.

Conclusions
High expression and accelerated efflux transporter activity of ABCG2/BCRP in the small intestine are expected to contribute to the ineffectiveness of orally administered intact tablets in cases with treatment-resistant Hashimoto’s thyroiditis, and crushed tablets can be more effective for some of these patients.