bluuebunny/crossref_metadata_2025_split huggingface dataset:
Receptor protein tyrosine phosphatase delta is not essential for synapse maintenance or transmission at hippocampal synapses
Authors: Han Kyung Ah , Lee Hee-Yoon , Lim Dongseok , Shin Jungsu , Yoon Taek Han , Liu Xinran , Um Ji Won , Choi Se-Young , Ko Jaewon 
Published: June 2020

AbstractMembers of the leukocyte common antigen-related receptor protein tyrosine phosphatase (LAR-RPTP) family, comprising PTPσ, PTPδ and LAR, are key hubs for presynaptic assembly and differentiation in vertebrate neurons. However, roles of individual LAR-RPTP members have not been investigated using member-specific conditional knockout mice. Here, we show that loss of PTPδ had no overt effect on synapse development in mouse cultured hippocampal neurons. Moreover, loss of PTPδ in presynaptic CA1 hippocampal neurons did not influence neurotransmitter release in subicular pyramidal neurons, suggesting that PTPδ is not critical for presynaptic function in vivo. Our results demonstrate that PTPδ is not essential for synapse maintenance or transmission, at least in the mouse hippocampus, and underscore the importance of using sophisticated genetic approaches to confirm the roles of synaptic proteins.
The lncRNA LAMP5-AS1 drives leukemia cell stemness by directly modulating DOT1L methyltransferase activity in MLL leukemia
Authors: Wang Wen-Tao , Chen Tian-Qi , Zeng Zhan-Cheng , Pan Qi , Huang Wei , Han Cai , Fang Ke , Sun Lin-Yu , Yang Qian-Qian , Wang Dan , Luo Xue-Qun , Sun Yu-Meng , Chen Yue-Qin 
Published: June 2020

Abstract
Background
Mixed-lineage leukemia (MLL) gene rearrangements trigger aberrant epigenetic modification and gene expression in hematopoietic stem and progenitor cells, which generates one of the most aggressive subtypes of leukemia with an apex self-renewal. It remains a challenge to directly inhibit rearranged MLL itself because of its multiple fusion partners and the poorly annotated downstream genes of MLL fusion proteins; therefore, novel therapeutic targets are urgently needed.

Methods
qRT-PCR, receiver operating characteristic (ROC), and leukemia-free survival analysis were used to validate LAMP5-AS1 (LAMP5 antisense 1) expression and evaluate its clinical value. We performed in vitro and in vivo experiments to investigate the functional relevance of LAMP5-AS1 in MLL leukemia progression and leukemia cell stemness. RNA electrophoretic mobility shift assays (EMSA), histone methyltransferase assay, RNA pull-down assay, and RNA fluorescence in situ hybridization (FISH) were used to validate the relationship between LAMP5-AS1 and the methyltransferase activity of DOT1L. The downstream ectopic target genes of LAMP5-AS1/DOT1L were validated by the chromatin immunoprecipitation (ChIP) and western blot.

Results
We discovered that a long noncoding RNA (lncRNA) LAMP5-AS1 can promote higher degrees of H3K79 methylation, followed by upregulated expression of the self-renewal genes in the HOXA cluster, which are responsible for leukemia stemness in context of MLL rearrangements. We found that LAMP5-AS1 is specifically overexpressed in MLL leukemia patients (n = 58) than that in the MLL-wt leukemia (n = 163) (p < 0.001), and the patients with a higher expression level of LAMP5-AS1 exhibited a reduced 5-year leukemia-free survival (p < 0.01). LAMP5-AS1 suppression significantly reduced colony formation and increased differentiation of primary MLL leukemia CD34+ cells. Mechanistically, LAMP5-AS1 facilitated the methyltransferase activity of DOT1L by directly binding its Lys-rich region of catalytic domain, thus promoting the global patterns of H3K79 dimethylation and trimethylation in cells. These observations supported that LAMP5-AS1 upregulated H3K79me2/me3 and the transcription of DOT1L ectopic target genes.

Conclusions
This is the first study that a lncRNA regulates the self-renewal program and differentiation block in MLL leukemia cells by facilitating the methyltransferase activity of DOT1L and global H3K79 methylation, showing its potential as a therapeutic target for MLL leukemia.
Hsa_circ_0003998 promotes epithelial to mesenchymal transition of hepatocellular carcinoma by sponging miR-143-3p and PCBP1
Authors: Song Li-na , Qiao Guang-lei , Yu Jian , Yang Chun-mei , Chen Ying , Deng Zhou-feng , Song Li-hua , Ma Li-jun , Yan Hong-li 
Published: June 2020

Abstract
Background
Circular RNAs (circRNAs) play a critical regulatory role in cancer progression. However, the underlying mechanisms of circRNAs in hepatocellular carcinoma (HCC) metastasis remain mostly unknown.

Methods
Has_circ_0003998 (circ0003998) was identified by RNAs sequencing in HCC patients with /without portal vein tumor thrombus (PVTT) metastasis. The expression level of circ0003998 was further detected by in situ hybridization on tissues microarray (ISH-TMA) and qRT-PCR in 25 HCC patients with PVTT metastasis. Moreover, the 25 HCC patients with PVTT metastasis and 50 HCC patients without PVTT metastasis were recruited together to analyze the correlation between circ0003998 expression and HCC clinical characteristics. Transwell, migration and CCK8 assays, as well as nude mice model of lung or liver metastasis were used to evaluate the role of circ0003998 in epithelial to mesenchymal transition (EMT) in HCC. The regulatory mechanisms of circ0003998 in miR-143-3p and PCBP1 were determined by dual-luciferase reporter assay, nuclear-cytoplasmic fractionation, fluorescent in situ hybridization, RNA pull- down, microRNA sequence, western blot and RNA immunoprecipitation.

Results
Compared with adjacent normal liver tissues (ANL), circ0003998 expression was significantly upregulated in PVTT tissues and HCC tissues, and its expression correlates with the aggressive characteristics of HCC patients. Further assays suggested that circ0003998 promoted EMT of HCC both in vitro and in vivo. Mechanistically, our data indicated that circ0003998 may act as a ceRNA (competing endogenous RNA) of microRNA-143-3p to relieve the repressive effect on EMT-related stimulator, FOSL2; meanwhile, circ0003998 could bind with PCBP1-poly(rC) binding protein 1 (PCBP1) to increase the expression level of EMT-related genes, CD44v6.

Conclusion
Circ0003998 promotes EMT of HCC by circ0003998/miR-143-3p/FOSL2 axis and circ0003998 /PCBP1/CD44v6 axis.
Long non-coding RNA THOR promotes ovarian Cancer cells progression via IL-6/STAT3 pathway
Authors: Ge Jing , Han Tao , Shan Lili , Na Jing , Li Ya , Wang Jun 
Published: June 2020

Abstract
Background
Ovarian cancer (OC) is one of the most common malignant tumors in the world. The prognosis of OC remains poor due to the advanced stage and distant metastasis at the time of diagnosis. Recently, a novel lncRNA, THOR (testis-associated highly conserved oncogenic long non-coding RNA), was characterized in human cancers and shown to exhibit an oncogenic role. However, the role of THOR in OC remains unclear.

Methods
RT-PCR and western blot analysis were used to detect the expression of THOR, p-STAT3 and IL-6. The impact of THOR on OC proliferation, metastasis and self-renewal was investigated in vitro and in vivo. The prognostic value of THOR was determined in OC patient cohorts.

Results
In this study, our results find that THOR is markedly upregulated in human OC tissues and predicts the poor prognosis of OC patients. Functional studies have revealed that knockdown of THOR inhibits the growth, metastasis and self-renewal of OC cells. Mechanistically, THOR drives OC cell progression via the IL-6/STAT3 signaling. Moreover, the specific STAT3 inhibitor S3I-201 or IL-6R inhibitor tocilizumab diminish the discrepancy in the growth, metastatic and self-renewal capacity between THOR-silenced OC cells and control cells, which further confirm that IL-6/STAT3 is required in THOR-driven OC cells progression.

Conclusion
Our findings reveal that THOR could promote OC cells growth, metastasis and self-renewal by activating IL-6/STAT3 signaling and may be a good predictive factor and therapeutic target.
Pure dysgerminoma of the ovary: CT and MRI features with pathological correlation in 13 tumors
Authors: Zhao Shuhui , Sun Fan , Bao Lei , Chu Caiting , Li Haiming , Yin Qiufeng , Guan Wenbin , Wang Dengbin 
Published: June 2020

Abstract
Background
To investigate the spectrum of CT and MRI findings of dysgerminoma of the ovary.

Methods
CT and MRI imaging of 12 patients with 13 histologically proven dysgerminomas of the ovary were retrospectively reviewed. Patients, ages ranged from 6 ~ 27 years (mean, 17.2 years). Two observers evaluated the following CT and MRI features of the tumor by consensus: (i) location, shape, and size; (ii) attenuation, T2 signal intensity, and ADC value; (iii) patterns of contrast enhancement; (iv) presence of fibrovascular septa; (v) presence of necrosis, hemorrhage, and calcification; (vi) presence of “ovarian vascular pedicle” sign. We also noted the extent or stage of the tumors.

Results
75% lesions arised in the right ovary. Bilateral ovaries were involved in one case. Tumors displayed as a purely or predominantly solid mass (mean size, 17.0 ± 7.8 cm). Ten tumors were shaped multilobulated. The mean ADC value of lesions was 0.830 ± 0.154 × 10− 3 mm2/s. Characteristic fibrovascular septa were observed in all lesions. Among them, classic septa were present in 69% lesions. They were thin, hypointense on T2WI with a linear intense enhancement indicating the blood vessels in septa. Due to the stromal edema, fibrovascular septa may become thick even amorphous in shape, hyperintense on T2WI and even low attenuation on CT with a slight enhancement except for a bright blood vessel on the edge. Massive necrosis was observed only in one lesion. Calcification was present in 3 of the 5 tumors on CT. “Ovarian vascular pedicle” sign was present in 12 lesions. Lymphadenopathy, retroperitoneal spread, and distant metastases combined with an implantation in Douglas’ cul-de-sac were present in one patient respectively.

Conclusion
On CT and MR images, ovarian dysgerminoma often appears as a large solid mass. The edematous condition of characteristic fibrovascular septa can be well displayed by imaging which then can guide the radiologists to make an accurate diagnosis. Calcifications often occur in the tumor. Nonspecific low ADC value and “ovarian vascular pedicle” sign may narrow the differential diagnosis.
Clinical inertia is the enemy of therapeutic success in the management of diabetes and its complications: a narrative literature review
Authors: Andreozzi F. , Candido R. , Corrao S. , Fornengo R. , Giancaterini A. , Ponzani P. , Ponziani M. C. , Tuccinardi F. , Mannino D. 
Published: June 2020

AbstractDiabetes mellitus is a chronic disease characterized by high social, economic and health burden, mostly due to the high incidence and morbidity of diabetes complications. Numerous studies have shown that optimizing metabolic control may reduce the risk of micro and macrovascular complications related to the disease, and the algorithms suggest that an appropriate and timely step of care intensification should be proposed after 3 months from the failure to achieve metabolic goals. Nonetheless, many population studies show that glycemic control in diabetic patients is often inadequate. The phenomenon of clinical inertia in diabetology, defined as the failure to start a therapy or its intensification/de-intensification when appropriate, has been studied for almost 20 years, and it is not limited to diabetes care, but also affects other specialties. In the present manuscript, we have documented the issue of inertia in its complexity, assessing its dimensions, its epidemiological weight, and its burden over the effectiveness of care. Our main goal is the identification of the causes of clinical inertia in diabetology, and the quantification of its social and health-related consequences through the adoption of appropriate indicators, in an effort to advance possible solutions and proposals to fight and possibly overcome clinical inertia, thus improving health outcomes and quality of care.
Immunohistochemical expression of Cyclin D1 among Sudanese patients diagnosed with benign and malignant prostatic lesions
Authors: Ahmed Eiman Siddig , Elnour Lubna S. , Hassan Rowa , Siddig Emmanuel E. , Chacko Mintu Elsa , Ali Eman T. , Mohamed Mona A. , Munir Abdalla , Muneer Mohamed S. , Mohamed Nouh S. , Edris Ali M. M. 
Published: June 2020

Abstract
Objectives
Prostate cancer (PC) is common cancer worldwide. Several markers have been developed to differentiate between benign prostatic hyperplasia (BPH) from PC. A descriptive retrospective hospital-based study aimed at determining the expression of Cyclin D1 in BPH and PC. The study took place at different histopathology laboratories in Khartoum state, Sudan, from December 2016 to January 2019. Formalin-fixed paraffin-embedded blocks were sectioned and fixed in 3-aminopropyltriethoxysilane coated slides incubated into primary antibody for Cyclin D1. The assessment of immunoreactivity of Cyclin D1 of each section was done using the Gleason scoring system.

Results
A total of 153 males’ prostate sections included in this study, of them, 120 (78.4%) were PC, and 33 (21.6%) were BPH. Their age ranged from 45 to 88 years, mean age was 66.19 ± 8.599. 142 (92.8%) did not have a family history of PC, while 11 (7.2%) patients reported having a family history. The Gleason scoring showed a total of 81 (52.9%) patients with high-grade and 39 (25.5%) with low-grade. 118 (97.5%) patients had PC showed positive results for Cyclin D1, while BPH was 3 (2.5%). P value < 0.001. Cyclin D1 staining was associated with high-grade Gleason score and perineural invasion, P value 0.001.
A rare case of anaphylaxis to Indian jujube (Ziziphus Mauritiana Lam)
Authors: Aberumand Babak , Borici-Mazi Rozita 
Published: June 2020

Abstract
Background
Indian jujube (Ziziphus Mauritiana Lam) is a sweet fruit from a tree native to tropical and subtropical regions of Asia and India. A few case reports have implicated Indian jujube to cause latex-fruit syndrome. We present the first case of an anaphylactic reaction to this fruit in a patient with no latex allergy.

Case presentation
A 55-year-old male was referred to the Outpatient Allergy Clinic at Queen’s University for evaluation of anaphylaxis caused by ingestion of Indian jujube. He presented to the Emergency Department (ED) with scalp pruritus, dyspnea and generalized urticaria, which occurred two hours after he had consumed a homemade candied fruit cocktail consisting of Indian jujube, water, Thai and Indian sweetener. In the ED, he was treated with epinephrine, intravenous diphenhydramine and steroids. He did not have any previous history of environmental or food allergies but had consumed this fruit frequently since childhood. In clinic, he underwent skin-prick testing with a saline slurry of candied jujube, which resulted in a positive wheal and flare response with appropriate controls. On subsequent visit, skin-prick tests were performed with saline slurries of the Thai and Indian sweetener used to make the cocktail. Both tests were negative when applied to a healthy volunteer. Skin-prick testing to latex allergen and latex specific IgE were both negative. He was diagnosed with an IgE-mediated anaphylactic reaction to the Indian jujube fruit. He was advised to avoid consumption of Indian jujubes and carry an epinephrine autoinjector.

Conclusions
Anaphylaxis secondary to Indian jujube ingestion is an extremely rare phenomenon in patients without a latex allergy. A possible allergy to Indian jujube should be taken into consideration when working up anaphylaxis, especially in patient of Asian and Indian descent who have ceased regular consumption of the fruit.
Atypical case of hantavirus infection in Sri Lanka mimicking leptospirosis: a case report
Authors: Dalugama Chamara , Nanayakkara Madushi , Rathnayaka Nimanthi , Medagama Arjuna 
Published: June 2020

AbstractBackgroundHantavirus infection is an emerging zoonotic infection which has two characteristic patterns of presentation: hantavirus pulmonary syndrome and hemorrhagic fever with renal syndrome. The clinical presentation of hantavirus infection closely mimics leptospirosis.Case presentationThis case report describes a previously apparently well 36-year-old Sri Lankan Sinhalese man who presented with an acute febrile illness with myalgia, with liver involvement in the form of transaminitis, cardiac involvement in the form of myocarditis, acute kidney injury, and pulmonary involvement. He was initially managed as severe leptospirosis with multiorgan dysfunction with antibiotics, steroids, and N-acetyl cysteine. A diagnosis of acute hantavirus infection was made subsequently. He made an uneventful recovery.ConclusionHantavirus infections need to considered in the differential diagnosis of patients presenting with acute febrile illness with multiorgan involvement. Larger studies are needed to evaluate the seroprevalence of hantavirus in Sri Lanka because it could be an emerging serious public health problem.
Time-dependent selected reaction monitoring-based GC-MS/MS method for estimation of genotoxic impurities in new antibacterial agent: alalevonadifloxacin mesylate
Authors: Ahirrao Vinod K. , Jadhav Rajiv A. , Rane Vipul P. , Bhamare Harshal R. , Yeole Ravindra D. 
Published: June 2020

AbstractAlalevonadifloxacin mesylate (ALA), pro-drug of levonadifloxacin is a new antibiotic approved in India to treat infections caused by Gram-positive bacteria. Alkyl mesylates (AMs) are known genotoxic impurities (GTI’s) formed in drug substances isolated as mesylate salts. Time-dependent selected reaction monitoring (t-SRM)-based gas chromatography tandem mass spectrometry (GC-MS/MS) method has been developed for trace estimation of AMs, namely, methyl methane sulfonate (MMS), ethyl methane sulfonate (EMS) and isopropyl methane sulfonate (IMS) in ALA. Liquid-liquid extraction (LLE) procedure using dichloromethane (DCM) as an extracting solvent was employed to extract AMs from the drug substance. Automatic selective reaction monitoring (auto-SRM) tool was applied to identify the most intense SRM pair of the ions to achieve the highest sensitivity. The method was validated in terms of specificity, linearity, sensitivity, precision, and accuracy. The limit of quantitation (LOQ) for the MMS, EMS and IMS were 5, 10, and 20 ng/g of ALA, respectively. For all analytes, the correlation coefficient (R) were greater than 0.9975 in the concentration range of 3.0–260 ng/mL. Mean recovery of all analytes was in the range of 91.77 to 97.65%.
Potentials of truffles in nutritional and medicinal applications: a review
Authors: Lee Heayyean , Nam Kyungmin , Zahra Zahra , Farooqi Muhammad Qudrat Ullah 
Published: June 2020

AbstractTruffles, the symbiotic hypogeous edible fungi, have been worldwide regarded as a great delicacy because of their unique flavor and high nutritional value. By identifying their bioactive components such as phenolics, terpenoids, polysaccharides, anandamide, fatty acids, and ergosterols, researchers have paid attention to their biological activities including antitumor, antioxidant, antibacterial, anti-inflammatory, and hepatoprotective activities. In addition, numerous factors have been investigating that can affect the quality and productivity of truffles to overcome their difficulty in culturing and preserving. To provide the information for their potential applications in medicine as well as in functional food, this review summarizes the relevant literature about the biochemical composition, aromatic and nutritional benefits, and biological properties of truffles. Besides, various factors affecting their productivity and quality as well as the preservation methods are also highlighted.
Resection of pancreatic and splenic metastases from alveolar soft part sarcoma: a case report
Authors: Arakawa Satoshi , Asano Yukio , Kawabe Norihiko , Nagata Hidetoshi , Kondo Yuka , Furuta Shinpei , Shimura Masahiro , Hayashi Chihiro , Ochi Takayuki , Kamio Kenshiro , Kawai Toki , Yasuoka Hironobu , Higashiguchi Takahiko , Ishihara Shin , Ito Masahiro , Imaeda Yoshihiro , Horiguchi Akihiko 
Published: June 2020

Abstract
Background
We present a case of pancreatic and splenic metastases following alveolar soft part sarcoma (ASPS), which was successfully treated by surgery.

Case presentation
A 41-year-old male was referred to our hospital in 2012. Computed tomography (CT) showed the presence of a pancreatic tumor. In 2002, the patient had undergone surgical resection of an ASPS of the anal region. In 2009, during follow-up, CT revealed lung metastases, which prompted surgical resection of the lung, followed by resection of the head skin in 2011. Abdominal ultrasonography (US) revealed the presence of isodense masses sized 34 mm in the pancreatic head and 60 mm within the spleen. The contrast-enhanced US revealed a solitary lesion with enhancement. Contrast-enhanced CT revealed solitary lesions with enhancement within the pancreatic head, spleen, and liver. The patient underwent metastasectomies from the pancreas, spleen, and liver. The patient was discharged on postoperative day 22 without recurrence for 18 months after metastasectomy. Twelve years after primary resection and 2 years after metastasectomy, the patient died as a consequence of multiple metastases.

Conclusions
We have presented a rare case of pancreatic and spleen metastases from ASPS. Resection by radical metastasectomy was successful without morbidity. Thus, for improved survival of patients with multiple metastases from ASPS, metastasectomy may be indicated. If multiple metastases are resectable, surgical approaches may be the preferred treatment.
Reducing instruments in a vitrectomy surgical tray: cost savings and results from a major academic hospital
Authors: Grodsky Jacob D. , Theophanous Christos N. , Schechet Sidney A. , Veldman Peter B. , Hariprasad Seenu M. 
Published: June 2020

Abstract
Background
Unused or rarely used instruments in standard surgical trays can unnecessarily increase costs. Prior studies have demonstrated the practicality and cost savings of reduced instrument tray sizes in various subspecialties. This study describes results and estimated cost savings from a reduced instrument tray used for vitrectomy surgery at a large, tertiary academic medical center.

Methods
Common usage patterns of vitrectomy instruments by one retina surgeon were reviewed and a reduced instrument vitrectomy tray was created and implemented in successive vitrectomy surgeries. Need for opening the previously utilized larger tray was recorded. Estimated cost savings of the new trays were calculated based upon per instrument sterilization, processing, and instrument replacement costs.

Results
New vitrectomy trays including just 7 instruments (89% reduction compared to original trays) were created and implemented in 189 successive cases. The original tray was never opened. Estimated cost savings from saved sterilization and processing resources is approximately $9588 per year. Assuming 5- and 10-year lifespan per instrument, annual cost avoidance is projected at $7886 and $15,772, respectively. Other indirect benefits relevant to healthcare quality were also noted.

Conclusion
A reduced instrument tray can be successfully implemented for vitrectomy surgery and can result in significant indirect benefits as well as direct cost savings from reduced sterilization costs. Our study highlights the substantial impact made by evaluating the usage pattern and making appropriate instrument tray changes for just one retina surgeon. Applying these same methods to other surgeons and specialties can have significant implications on healthcare costs and quality.