bluuebunny/crossref_metadata_2025_split huggingface dataset:
ML-12 MECHANISMS OF CELL DEATH INHIBITION THROUGH CHANGE IN SUBCELLULAR LOCALIZATION OF PIM-1 BY PIM1 GENE MUTATION RECURRENTLY FOUND IN PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMA
Authors: Sasaki Nobuyoshi , Ichimura Koichi , Nagane Motoo , Tomiyama Arata 
Published: December 2019

Abstract

BACKGROUNDS
In a study of Next Generation Sequencing in primary central nervous system lymphoma (PCNSL), we have previously reported several mutations of high frequency, in comparison with systemic diffuse large B cell lymphoma (DLBCL)s. Consequences of these specific mutations in PCNSL are unknown. In this study, we have analyzed the functional consequence of mutations in the PIM1 gene, observed in 100% of PCNSL patients, which encodes a serine/threonine kinase and is known to drive tumorigenesis in several malignancies.

METHODS
Four most frequent mutations of PIM1 in PCNSL, S77N, K115N, P216S, L275F, were chosen from our previous study, and each mutant was generated by site directed mutagenesis in PIM1 cDNA cloned in an expression vector. Resulting vectors were transiently transfected into human cancer cell lines. Functional studies were carried out using various biochemical methods.

RESULTS
Among the four mutants, increased phosphorylation of BCL-2 associated death promoter (BAD) at Ser112, which is a phosphorylation target of Pim-1, was observed by expression of K115N mutant compared with wild type PIM1 in Hela and Nagai cells expressing endogeneous BAD. Decreased cell death under campthothecin treatment was also observed in K115N mutant expressing Nagai cells compared with wild type PIM1-expressed cells. We also observed a significant shift in subcellular localization of Pim-1 carrying K115N mutant; from the nucleus, main sublocalization for wild type Pim-1, into the cytosol determined by immunocytochemistry and immunoblotting of nuclear and cytosolic fraction of the cells. Augmented cytosolic localization of Pim-1 carrying K115N mutant was suppressed by inhibition of glycosylation.

DISCUSSION
It is suggested that PIM1 K115N mutant may drive chemoresistance through increased BAD phosphorylation that suppresses cell death compared with wild-type PIM1 through modification of its subcellular localization, which might be regulated by its glycosylation status.
MET-05 PRELIMINARY REPORT OF RADIOTHERAPY FOR BRAIN METASTASES FROM GASTRO-INTESTINAL CANCERS USING MASK SYSTEM OF LEKSELL GAMMA KNIFE ICON
Authors: Kawabe Takuya , Sato Manabu 
Published: December 2019

Abstract

OBJECT
Leksell Gamma Knife Icon enables us to apply new methods of immobilization using mask fixation and the option of fractionated treatment. This provides exceptional accuracy and precision of radiosurgery, making it a possibility for many more disease types and many more patients to be treated.

METHODS
We retrospectively analyzed 50 patients (71 times) with brain metastases from gastro-intestinal cancers who underwent Gamma Knife Icon using mask fixation between September 25th, 2017 and June 30th, 2019 at Rakusai Shimizu Hospital. Patients with small, few, newly diagnosed, and non-eloquent area tumors were treated in a single session. If the tumor volume was larger than 5.0 ml, recurrence, or the location was in an eloquent area, we applied a fractionated schedule. If the tumor number was large, we selected a multisession schedule. The most common origin was colon (19 patients), followed by rectum (11), stomach (7), esophagus (5) and others (8).

RESULTS
13 cases were treated in a single session, 53 with fractionation, and five with multiple sessions. We selected fractionated schedules as follows; 7.0 Gy x 5Fr (5–10 ml), 4.2Gy x 10Fr (10-20ml), 3.7Gy x 10Fr (20-30ml), 3.2Gy x 10Fr (30ml-) for malignant tumors, and 2.7Gy x 10Fr for benign tumors. Median tumor number was two (1–40) and median tumor size was 8.1 (0.03–67.5) ml. Median survival times after Icon treatment was 13.5 months and local control rate after 6-month Icon treatment was 80%.

CONCLUSIONS
Although these results are limited to short periods, survival rates, local control rates and qualitative survival rated in patients unsuitable for stereotactic radiosurgery, such as those with large, recurrent, and eloquent site lesions, were within the acceptable ranges.
BT-02 MULTIDISCIPLINARY TREATMENT FOR EPENDYMOMA
Authors: Hirokawa Daisuke , Hayashi Tomoko , Sato Hironobu , Keino Dai , Yokosuka Tomoko , Gotou Hiroaki , Yamamoto Tetsuya 
Published: December 2019

Abstract

BACKGROUND
In intracranial ependymoma, the effectiveness of chemotherapy and radiation therapy is unclear, and the degree of tumor removal contributes to the improvement of life prognosis. Methods: We examined ependymoma cases treated in our institution from July 1998 to March 2017.

RESULTS
There were 18 boys and 7 girls. The average age at the time of surgery is 5.3 ± 3.6 years. The pathological diagnosis was Grade II for 8 cases and Grade III for 17 cases. Genetic analysis was performed in 16/25 cases (64%). Of the infratentorial cases, 10/11 cases (90.1%) were PFA and PFB were one case. Of the supratentorial cases, 3/5 cases (60%) were positive for RELA fusion. As chemotherapy, 19 patients were VCR + VP-16 + CDDP + CPA. Irradiation was performed in all cases, local irradiation (50.4–55.8Gy) in 22 cases (88%), and craniospinal irradiation in 2 cases (8%). The 7-year OS was 74.6 ± 9% and the 7-year PFS was 59.7 ± 10.5%. Grade III showed a short OS (p = 0.053). GTR and NTR were obtained in the first excision in 14 cases (56%), and OS and PFS were not significantly different from those in the STR group (p = 0.219, p = 0.248). GTR and NTR including 2nd-look surgery were obtained in 18 cases (72%), and significant improvement of OS was observed compared with STR group (p = 0.02). In patients with hydrocephalus preoperatively, OS tended to be short (p = 0.057), especially in cases requiring VP shunt placement, OS was significantly shortened (p = 0.017).

CONCLUSION
Even if it is not GTR or NTR at the first operation, improvement of OS is expected by total excision after chemotherapy. The importance of chemotherapy was suggested to be suppression of tumor growth until reoperation and reduction of blood loss during surgery.
BT-06 CENTRAL NERVOUS SYSTEM HEMANGIOBLASTOMA; DIFFERENCES IN CLINICAL PICTURE OF SPORADIC CASES AND VON-HIPPEL LINDAU DISEASE IN 184 CASES
Authors: Takami Hirokazu , Burns Terry , Parney Ian 
Published: December 2019

Abstract

INTRODUCTION
Central nervous system hemangioblastoma (CNS HGB) is a rare neoplasm, which predominantly arise in the posterior fossa and spinal cord. The etiology is divided into sporadic and von-Hippel Lindau (VHL) disease. The difference in clinical picture of these 2 types of HGB and differentiation of treatment have not been extensively unraveled yet.

METHODS
Retrospective analysis of consecutive, neurosurgically managed CNS HGB at Mayo Clinic, 1988–2018.

RESULTS
117 sporadic and 67 VHL HGBs were treated by Mayo Clinic. No significant difference in sex was observed. Compared with sporadic cases, VHL cases were younger (51.8 vs 36.0 years old, p&lt;0.0001), had more frequent family history (0.0 vs 41.5 %, p&lt;0.0001), and higher frequency of germline alteration (0.0 vs 84.2 %, p&lt;0.0001). Regarding imaging findings, VHL cases had multiple lesions at presentation more frequently (3.4 vs 82.1 %, p&lt;0.0001), it was more common for sporadic lesions to contain cysts (72.2 vs 51.0 %, p=0.0004), the solid portion rate in the entire lesion was larger in VHL lesions (60.2 vs 69.5 %, p=0.02), and the volume was larger in sporadic cases (15.1 vs 6.6 cc, p&lt;0.0001). Regarding treatment, 131 and 123 surgeries were performed for sporadic and VHL cases, respectively, among which the indication of surgery was preventative in 8.4 and 47.3 %, respectively (p&lt;0.0001). VHL cases had higher number of treatments per case in the follow-up (1.3 vs 2.1, p&lt;0.0001). Recurrence-free survival of sporadic cases was significantly longer than that of VHL cases (p=0.007) and overall survival was longer in sporadic cases than VHL, but not significant (p=0.07).

CONCLUSION
Clinical presentation and tumor appearance on imaging are highly dependent on the etiology. Differences in clinical manifestations require further study, but may reflect contrasting tumor biology that are tied to genetic differences.
CS-08 A CASE OF CD 57 NEGATIVE OLFACTORY GROOVE SCHWANNOMA IN WHICH SCHWANN / 2 E AND SOX10 WAS USEFUL FOR DISTINGUISHING FROM OEC TUMOR: A CASE REPORT AND REVIEW OF THE LITERATURES
Authors: Masuda Hiroyuki , Nemoto Masaaki , Matsuzaki Ryo , Matsura Chie , Terazono Sayaka , Mikai Masataka , Ando Shumpei , Harada Masasi , Kondo Kosuke , Harada Naoyuki , Sugo Nobuo 
Published: December 2019

Abstract

INTRODUCTION
In the case of the differentiate between olfactory groove schwannomas(OGS) and olfactory ensheathing cell (OEC) tumors, CD57 which is the marker which is specific for Schwann cell is useful. We experienced a case of OGS that was negative for CD57.

CASE PRESENTATION
This case was a 13-year-old girl. Medical history: She visited the pediatric department with a chief complaint of headache. On the magnetic resonance image (MRI), a tumorous lesion was found in the anterior skull base and was referred to our department. No dysosmia, visual impairment, or cafe au lait spots were observed. Past history: As a medical history, she has developed acute lymphocytic leukemia at the age of 1 and has achieved complete remission after chemotherapy. At that time, radiation treatment to the head was not performed. Neuroradiological findings: The tumor was strongly enhanced heterogeneously in Gadolinium (Gd) enhanced MRI and the angiography showed hypovascular. Progress after hospitalization: The tumor was clearly demarcated from the surrounding brain surface and adhered strongly to the cribriform plate. Eventually, all tumors were removed and the patient was discharged on the 10th postoperative day. Five years have passed since the operation, and no recurrence of the tumor has been confirmed by MRI. Pathological findings: Antoni A and Antoni B were seen by Hematoxylin & Eosin (H & E) staining. Immunostaining showed S-100 strong positive, Schwann / 2E and Sox10 positive, and CD57 negative. Discussion: In our case, CD57 (Leu7) was negative, but Schwann / 2E and Sox10 were positive, so OGS was diagnosed.

CONCLUSION
We experienced a case of OGS that was negative for CD57 (Leu7) but positive for Schwann / 2E and Sox10. For pathological differentiation between OGS and the OEC tumor, Schwann / 2E and Sox10 immunostaining would also be necessary in addition to H & E stain and CD57 (Leu7).
COT-20 PERIOPERATIVE STATUS OF SERUM D-DIMER LEVEL AND VENOUS THROMBOSIS IN PATIENTS WITH MALIGNANT BRAIN TUMOR
Authors: Shimada Daisuke , Kobayashi Keiichi , Saito Kuniaki , Matsumoto Yoshie , Iijima Shohei , Shiokawa Yoshiaki , Nagane Motoo 
Published: December 2019

Abstract

BACKGROUNDS
The patients with malignant brain tumors frequently show the hypercoagulability state and a decrease in fibrinolysis ability with an elevation in D-dimer. This is partially due to tumor-related hemiparesis or surgical stress including long-term bed-ridden positioning during and after operation,which could lead to development and extension of deep venous thrombosis (DVT) in lower extremities and eventually fatal pulmonary embolism.

METHODS
We retrospectively examined the pre- and postoperative serum D-dimer levels and DVT state in 75 consecutive patients with malignant brain tumors (i.e. glioma,malignant lymphoma; mean age 64 yo,28 females) operated at our hospital from January 2015 to April 2017. Serial D-dimer levels were measured with the latex agglutination method (Roche) at 2 days before and right after operation,postoperative day (POD) 1,3,and 7. Lower limb venous ultrasound (LVUS) or contrast CT was performed if preoperative D-dimer was 0.5μg/ml or higher.

RESULTS
Average BMI was 21.3,nine patients with diabetes mellitus,10 had recurrent diseases after chemotherapy,and 10 presented paresis in the lower extremities preoperatively while two developed transient paresis postoperatively. While two patients had prior DVT history,central and calf DVTs were identified preoperatively in one and 12 (15%) patients,respectively. Among four patients with re-elevation of D-dimer after POD 7,infection (2 patients),new DVT (2),and hemorrhagic events (gastrointestinal 2,including 1 death; epistaxis 2) developed,where a cut-off value D-dimer &gt; 1.69 yielded sensitivity 100% and specificity 80%. Intraoperative intermittent calf compression prevented perioperative pulmonary embolism in those with calf DVT.

CONCLUSIONS
Appropriate perioperative DVT managements could prevent development of pulmonary embolisms in all patients with”high-risk” malignant brain tumors. Not only D-dimer &gt; 1.5,but age of 80 or older,high preoperative D-dimer levels with calf DVT and taking DOAC may be risk factors for postoperative venous thromboembolism.
Nitrogen Fertilization Reduces Nitrogen Fixation Activity of Diverse Diazotrophs in Switchgrass Roots
Authors: Bahulikar Rahul A. , Chaluvadi Srinivasa R. , Torres-Jerez Ivone , Mosali Jagadish , Bennetzen Jeffrey L. , Udvardi Michael 
Published: December 2019

The use of synthetic nitrogen fertilizers to grow biofuel crops adds to the economic and environmental costs of biomass production. Biological nitrogen fixation provides an alternative, eco-friendly source of nitrogen for leguminous plants and some nonlegumes. With the objective of characterizing and eventually harnessing nitrogen-fixing bacteria in switchgrass roots, we assayed nitrogenase activity and surveyed nifH-expressing bacteria in roots of switchgrass grown under agricultural conditions. Plants were cultivated at two separate locations in Oklahoma in different soil types for 5 years with three nitrogen fertilizer regimes (0, 90, and 180 kg of N ha−1 year−1). Nitrogenase activity associated with roots cleaned of soil was found to be highest in plants grown with no N fertilizer and lowest or not detectable for plants grown at the highest level of N fertilizer. A total of 454 abundant nifH operational taxonomic units (OTUs) were identified in the switchgrass roots. Diversity analysis of active nifH-expressing bacteria showed that the most common orders were Burkholderiales (171 OTUs), Desulfovibrionales (55 OTUs), and Rhizobiales (44 OTUs). OTUs belonging to Azonexus, Pseudacidovorax, Desulfovibrio, Dechloromonas, and Bradyrhizobium were enriched in roots of plants grown under low nitrogen conditions. Analysis of significant OTUs showed distinct nifH-expressing microbial communities at the two field locations, as well as a unique community in roots of unfertilized soil at Frederick that exhibited the highest rates of nitrogen fixation. [Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Intensive Care Neonates and Evidence to Support the Elimination of Hats for Safe Sleep
Authors: Fulmer Megan , Zachritz Whitney , Posencheg Michael A. 
Published: December 2019

Background:
Although the incidence of sudden unexplained infant deaths has decreased over time with the use of safe sleep practices, one area that remains unclear is the safety of hats during infant sleep.

Purpose:
Decrease the risk of overheating or suffocation by removing NICU infants' hats during sleep without increasing the relative risk of hypothermia during transition to an open crib.

Methods:
Removal of hats for routine thermoregulation, beyond the initial infant resuscitation and stabilization of NICU infant was implemented in 2015. Retrospective chart audits were conducted on all NICU infants between February 2015 and December 2016. Hypothermia (≤ 97.6°F) data during transition to an open crib was collected. Exclusion criteria included concurrent diagnosis of: sepsis, hyperbilirubinemia, congenital anomaly inhibiting infants thermoregulation and noncompliance with unit guideline for weaning infant to open crib.

Findings:
Over 18 months, 2.7% of infants became hypothermic (≤ 97.6°F) during transition to open crib, requiring return to isolettes.

Implications for Practice:
Hats were found to be unnecessary in maintaining thermoneutrality after weaning infants toan open crib in our NICU. By avoiding the use of hats in an open crib, it's possible infants will avoid overheating and a risk of suffocation, creating a safer sleep environment.

Implications for Research:
The removal of hats during sleep to promote infant health should be considered for all infants.
Debates in gout management
Authors: Abhishek Abhishek 
Published: December 2019

Purpose of review
This review discusses the findings of recently published translational research studies that have the potential to directly impact on the management of gout patients.

Recent findings
Recent research suggests that treat-to-target urate-lowering treatment (ULT) alongside individualized education about gout, and shared decision making results in excellent adherence with ULT and prevents gout flares in the long term. Such interventions should preferentially be delivered face-to-face rather than remotely. The recently published CARES study raises the possibility that febuxostat increases the risk of death in people with preexisting major cardiovascular diseases, and, allopurinol should remain the first-choice ULT. There is paucity of data on the dosing of ULT for managing hyperuricaemia in gout patients with chronic kidney disease. However, recent research suggests that the dose of allopurinol can be gradually increased to above the conventional renal dose in people with chronic kidney disease without allopurinol hypersensitivity syndrome. However, additional larger studies are needed in this field.

Summary
In summary, long-term treat-to-target ULT prevents gout flares and improves quality of life. Given the recent safety concerns, gradually up-titrated allopurinol remains the first-line urate-lowering drug.
Should Thoracolumbar Junction Be Always Avoided as Upper Instrumented Vertebra in Long Instrumented Fusion for Adult Spinal Deformity?
Authors: Park Se-Jun , Lee Chong-Suh , Park Jin-Sung , Lee Kyung-Jun 
Published: December 2019

Study Design.
Retrospective study.

Objective.
The aim of this study was to investigate the risk factors for proximal junctional failure (PJF) following long instrumented fusion stopping at thoracolumbar junction (TLJ) in adult spinal deformity (ASD) and to determine which cases are suitable for TLJ stop without increasing the risk for PJF.

Summary of Background Data.
PJF following long fusion for ASD is a well-recognized complication that negatively affects clinical outcomes. Generally, the uppermost instrumented vertebra (UIV) at the TLJ is associated with the risk of PJF. Little is known about the risk factors for PJF in case with the UIV at TLJ.

Methods.
Radiographic and clinical data of 63 consecutive patients who underwent instrumented fusion from sacrum to TLJ (T11, T12, and L1) for the treatment of ASD with a minimum 2-year follow-up were analyzed to identify the risk factors for PJF, which was defined as proximal junctional angle (PJA) ≥20°, fracture at UIV or UIV+1, failure of UIV fixation, myelopathy, or ‘need for proximal extension of fusion.

Results.
During the average follow-up duration of 51.7 months, PJF developed in 23 patients (36.5%) at a mean of 9.3 months after surgery. Multivariate analysis revealed that age >70 years (odds ratio [OR]: 1.119), osteoporosis (OR: 4.459), and preoperative kyphotic PJA (OR: 1.138) were significant risk factors for the development of PJF. No PJF occurred in 14 patients lacking any risk factors. The last follow-up clinical results were significantly inferior in the PJF group than in the non-PJF group in terms of Oswestry Disability Index and Scoliosis Research Society-22 score.

Conclusion.
Age >70 years, osteoporosis, and PJA greater 0° were identified as significant risk factors for PJF. Therefore, the TLJ level can be considered as UIV selectively for patients younger than 70 years without osteoporosis and with lordotic preoperative PJA.

Level of Evidence: 3
DIABETIC MACULAR ISCHEMIA
Authors: Tsai Andrew S. H. , Gan Alfred T. L. , Ting Daniel S. W. , Wong Chee Wai , Teo Kelvin Y. C. , Tan Anna C. S. , Lee Shu Yen , Wong Tien Yin , Tan Gavin S. W. , Gemmy Cheung Chui Ming 
Published: December 2019

Purpose:
To examine the relationship between macular microvasculature parameters and functional changes in persons with diabetic retinopathy (DR).

Methods:
Cross-sectional study of 76 eyes with varying levels of DR. Optical coherence tomography angiography (OCTA) quantified superficial and deep perifoveal vessel densities and foveal avascular zone areas. Retinal sensitivity was measured using microperimetry. Optical coherence tomography angiography parameters and retinal sensitivity were correlated.

Results:
Deep perifoveal vessel density decreased with increasing severity of DR (adjusted mean 51.93 vs. 49.89 vs. 47.96, P-trend = 0.005). Superficial and deep foveal avascular zone area increased with increasing DR severity (adjusted mean: 235.0 µm2 vs. 303.4 µm2 vs. 400.9 µm2, P-trend = 0.003 [superficial]; 333.1 µm2 vs. 513.3 µm2 vs. 530.2 µm2, P-trend = 0.001 [deep]). Retinal sensitivity decreased with increasing DR severity (adjusted mean: 25.12 dB vs. 22.34 dB vs. 20.67 dB, P-trend = 0.003). Retinal sensitivity correlated positively with deep perifoveal vessel density (Pearson's ρ = 0.276, P = 0.020) and inversely with superficial foveal avascular zone area (Pearson's ρ = −0.333, P = 0.010).

Conclusion:
Alterations in retinal microvasculature can be observed with OCTA with increasing severity of DR. These changes are correlated with reduced retinal sensitivity. Optical coherence tomography angiography is useful to detect and quantify the microvasculature properties of eyes with diabetic macular ischemia.
OPTICAL COHERENCE TOMOGRAPHY AND OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FINDINGS AND VISUAL PROGNOSIS IN TWO PATIENTS WITH POSTERIOR MICROPHTHALMOS
Authors: Pineles Stacy L. , Davila-Gonzalez Juan P. , Gorin Michael , Lee Hane , Sarraf David , Velez Federico G. 
Published: December 2019

Background/Purpose:
Posterior microphthalmos is a rare ocular condition characterized by a disproportionately small posterior segment and multiple retinal abnormalities. The diagnosis can be challenging, and novel findings on optical coherence tomography (OCT) angiography may help to identify this unusual disorder. The purpose of this study is to report OCT and OCT angiography findings in two siblings with posterior microphthalmos.

Methods:
Case series at an academic eye institute including two affected siblings with posterior microphthalmos.

Results:
The results of OCT testing in two siblings with posterior microphthalmos illustrated bilateral papillomacular retinal fold and loss of the foveal depression. Optical coherence tomography angiography findings included loss of the foveal avascular zone and complete vascularization across the fovea.

Conclusion:
Unique OCT angiography findings in posterior microphthalmos are described herein. These findings may support the diagnosis of posterior microphthalmos and aid in the understanding of the pathogenesis of this disease.