bluuebunny/crossref_metadata_2025_split huggingface dataset:
ML-14 Re-challenge and maintenance therapy of methotrexate for elderly PCNSL patients with low scored KPS
Authors: Yamaguchi Takashi , Nagayama Rie , Gomi Akira , Kawai Kensuke 
Published: November 2020

Abstract
Purpose: The delayed neuronal toxicity after high dose methotrexate (HD-MTX) followed by radiotherapy (RT) is a serious problem for elderly primary CNS lymphoma patients. We started maintenance therapy (MT) with MTX after achieving complete remission (CR) to defer RT for elderly and poor Karnofsky Performance Scale (KPS) patients.
Methods: We performed HD-MTX (3.5g/m2) therapy until achieving CR for the patients over 70 years whose KPS were equal to or less than 60%. After having CR, 3 courses of MT of MTX (3g/patient) for 3 weeks were introduced every 3–4 months for 2 years. At the time of recurrence, HD-MTX was repeated. But when CR was not achieved by HD-MTX alone, RT was introduced. Moreover, additional use of rituximab was considered if patients’ condition became better.
Results: Number of patients was 9. Median age, median KPS, and median follow up periods were 73y.o. (71–78), 40% (30–60), and 14.0 months (1–55), respectively. CR rate was 78% and two patients were not achieved CR due to the adverse events (AEs) which were acute tubular necrosis and pneumocystis pneumonia. But meanwhile, there was no AE by MT. Median OS, median PFS, median time of radiation free period and delayed neuronal toxicity were 19.5 months (95%CI 3-NA), 5.0 months (95%CI 2–22), 2.5 months, and 8.2 months, respectively.
Discussion: The results of this study might be inferior to other reports of elderly patients due to poor median KPS. And low introduction rate of MT was undesirable. However, once MT was introduced, MT itself was safe and easy to manage and the long-term prognosis was excellent.
Conclusion: Rechallenge of HD-MTX and maintenance therapy of MTX might be promising but the problems of some serious AEs and low CR rate with HD-MTX alone should be resolved.
ML-18 Clinical diagnosis for suspected primary central nervous system lymphoma patients without histopathological confirmation
Authors: Osawa Sho , Horiguchi Keishi , Tosaka Masahiko , Yoshimoto Yuhei 
Published: November 2020

Abstract
Background: The gold standard of the diagnosis of primary central nervous system lymphoma (PCNSL) is the histopathological diagnosis by biopsy surgery. However, we experience some cases with a high risk of biopsy surgery or difficulty in general anesthesia. We perform radiation and chemotherapy without histopathological confirmation for such patients based on imaging findings, ophthalmological evaluation, and cerebrospinal fluid examinations. In this study, we investigated clinical diagnosis and outcomes for patients suspected PCNSL.
Method: From April 2016 to December 2019, all adult brain tumor patients that were diagnosed with PCNSL without histopathological confirmation and underwent radiation and/or chemotherapy were included. The following criteria were retrospectively analyzed. 1) Intraorbital lymphoma, 2) SUVmax&gt;12 in 18F FDG-PET, 3) ADCmean&lt;0.98×10–3 mm2/s in MRI diffusion-weighted images, 4) tumor to normal ratio &gt;1 in late phase of 123I IMP SPECT, 5) CSF β2 microglobulin &gt;2.1 mg/l, 6) CSF sIL2R &gt;77 U/ml, 7) Improvement of imaging findings or clinical symptoms by steroid.
Result: 9 suspected PCNSL patients were included. 8 patients were positive for 3 or more above criteria. All these patients achieved CR by initial treatment with radiation or chemotherapy which indicated appropriate diagnosis for PCNSL. The remaining 1 patient was SD by radiotherapy, which was an atypical clinical course of PCNSL. The above criteria were positive in 2 and negative in 3. There were no examinations that could be performed in all cases before the treatment.
Conclusion: Some useful markers for the diagnosis of PCNSL have been reported. However, all have limited sensitivity and specificity. Each examinations are also restricted by patient, institution and time. The combination of the useful examinations will improve the diagnostic accuracy of PCNSL.
CS-01 Rapid Recurrence and Anaplastic Transformation of a Pilocytic Astrocytoma in an Elderly Patient
Authors: Tanaka Toshihide , Teshigawara Akihiko , Tochigi Satoru , Hasegawa Yuzuru , Takei Jun , Akasaki Yasuharu , Murayama Yuichi , Yokoo Hideaki 
Published: November 2020

Abstract
BACKGROUND: Rapid recurrence of a pilocytic astrocytoma with anaplastic transformation is extremely rare. The case of an elderly patient with a cerebellar pilocytic astrocytoma with anaplastic transformation during short-term follow-up is reported. CASE DESCRIPTION: An 83-year-old woman presented initially with dizziness and a gait deviation to the right. Magnetic resonance imaging (MRI) demonstrated a homogeneously enhanced mass in the right cerebellar hemisphere, and the tumor was subtotally removed by right suboccipital craniotomy. Histological examination showed that the tumor cells contained eosinophilic cytoplasm and spindle-shaped processes with Rosenthal fibers and eosinophilic granular bodies, diagnosed as a typical pilocytic astrocytoma (PA). The MIB-1 index was less than 1%. The patient did not receive postoperative adjuvant radiation and chemotherapy. Two months after surgery, MRI showed growth of the residual tumor adjacent to the fourth ventricle, causing obstructive hydrocephalus. She underwent surgery again, and the tumor was totally removed. Histological findings showed mitotic cells and increased cellularity compared with the primary tumor, which was compatible with anaplastic transformation of PA with a MIB-1 index of 50%. Postoperatively, she was observed with best supportive care without postoperative adjuvant therapy. Nine months after the second operation, she died due to tonsillar herniation and obstructive hydrocephalus caused by a recurrent tumor. An autopsy was performed. CONCLUSION: It is extremely rare, as in the present case, that a cerebellar PA in an elderly patient recurs rapidly with anaplastic transformation, despite deferred postoperative adjuvant therapy including radiation and chemotherapy A novel molecular-targeted therapy is needed for anaplastic PA showing aggressive biological behavior.
COT-04 Circulating biomarker for glioblastoma and primary central nervous system lymphoma -Next Generation Sequencing of small noncoding RNA-
Authors: Onishi Shumpei , Yamasaki Fumiyuki , Takano Motoki , Yonezawa Ushio , Sugiyama Kazuhiko , Tahara Hidetoshi 
Published: November 2020

Abstract
Objective: Glioblastoma (GBM) and Primary Central Nervous System Lymphoma (PCNSL) are common intracranial malignant tumors. They sometimes present similar radiological findings and diagnoses could be difficult without surgical biopsy. For improving the current management, development of non-invasive biomarkers are desired. In this study, we explored the differently expressed circulating small noncoding RNA (sncRNA) in serum for specific diagnostic tool of GBM and PCNSL. Material & Methods: Serum samples were obtained from three groups: 1) GBM patients (N=26), 2) PCNSL patients (N=14) 3) healthy control (N=114). The total small RNAs were extracted from serum. The whole expression profiles of serum sncRNAs were measured using Next-Generation Sequencing System. We analyzed serum levels of sncRNAs (15–55 nt) in each serum samples. The difference of sncRNAs expression profile among three groups were compared. Data analysis was performed by logistic regression analysis followed by leave-one-out cross-validation (LOOCV). The accuracy of diagnostic models of sncRNAs combination were evaluated by receiver operating characteristic (ROC) analysis. Results: We created the combination models using three sncRNA in each models based on the logistic regression analysis. The model 1 (based on sncRNA-X1, X2 and X3) enabled to differentiate GBM patients form healthy control with a sensitivity of 92.3% and a specificity of 99.2% (AUC: 0.993). The model 2 (based on sncRNA-Y1, Y2 and Y3) enabled to differentiate PCNSL patients form healthy control with a sensitivity of 100% and a specificity of 93.9% (AUC: 0.984). The model 3 (based on sncRNA-Z1, Z2 and Z3) enabled to differentiate GBM patients form PCNSL patients with a sensitivity of 92.3% and a specificity of 78.6% (AUC: 0.920). Conclusion: We found three diagnostic models of serum sncRNAs as non-invasive biomarkers potentially useful for detection of GBM and PCNSL from healthy control, and for differentiation GBM from PCNSL.
COT-05 Experience of fertility preservation in 3 male cases and 1 female case with high-grade glioma
Authors: Nakayama Noriyuki , Yamada Tetsuya , Yano Hirohito , Kato Yuki , Iwama Toru 
Published: November 2020

Abstract
High-grade glioma (HGG) has a low survival rate, and fertility preservation (FP) has rarely been discussed in the field of Japanese neurosurgery. We report on 4 reproductive patients, including 2 male patients who became biological fathers. Case 1 was a 23-year-old man with anaplastic oligodendroglioma (AO) of the right frontal lobe. Temozolomide maintenance therapy (TMZ-MT) was completed 42 courses after the initial surgery for economic reasons. 21 months later, a local recurrent lesion appeared, so TMZ-MT was restarted after removal this lesion. When he married at 32 years old, the couple wished a desire for childbearing. The TMZ-MT was stopped at 47 courses from the resumption and they aimed for spontaneous pregnancy. At 5 months after discontinuation of TMZ-MT, Gd-enhanced lesions increased again, so we changed the course to in vitro fertilization and resumed TMZ-MT. The couple had a biological baby at his 33 years and 10 months old. Case 2 was a 33-year-old married man with AO of the right parietal lobe. After partial removal, the FP information was explained and cryopreservation of sperm was performed. As of 23 months after the first operation, he became a biological father by in vitro fertilization. Case 3 was a 31-year-old married man with diffuse midline glioma (H3K27M mutant) in the cervical spinal cord. After partial removal, we provided FP information in the same manner, but the couple did not chose cryopreservation of sperm due to his mRS 5. Case 4 was a 24-year-old female with anaplastic astrocytoma of the brain stem. FP information was provided after stereotactic biopsy, but she chose to start radiochemotherapy without cryopreservation of eggs. Patients of reproductive age with HGG, especially oligodendroglial tumors who have a higher survival rate than astrocytic tumors, should be positively informed about FP before treatment begins.
Identifying the Best Questions for Rapid Screening of Secondhand Smoke Exposure Among Children
Authors: Ksinan Albert J , Sheng Yaou , Do Elizabeth K , Schechter Julia C , Zhang Junfeng (Jim) , Maguire Rachel L , Hoyo Cathrine , Murphy Susan K , Kollins Scott H , Rubin Bruce , Fuemmeler Bernard F 
Published: November 2020

Abstract

Introduction
Many children suffer from secondhand smoke exposure (SHSe), which leads to a variety of negative health consequences. However, there is no consensus on how clinicians can best query parents for possible SHSe among children. We employed a data-driven approach to create an efficient screening tool for clinicians to quickly and correctly identify children at risk for SHSe.

Methods
Survey data from mothers and biospecimens from children were ascertained from the Neurodevelopment and Improving Children’s Health following Environmental Tobacco Smoke Exposure (NICHES) study. Included were mothers and their children whose saliva were assayed for cotinine (n = 351 pairs, mean child age = 5.6 years). Elastic net regression predicting SHSe, as indicated from cotinine concentration, was conducted on available smoking-related questions and cross-validated with 2015–2016 National Health and Nutrition Examination Survey (NHANES) data to select the most predictive items of SHSe among children (n = 1670, mean child age = 8.4 years).

Results
Answering positively to at least one of the two final items (“During the past 30 days, did you smoke cigarettes at all?” and “Has anyone, including yourself, smoked tobacco in your home in the past 7 days?”) showed area under the curve = .82, and good specificity (.88) and sensitivity (.74). These results were validated with similar items in the nationally representative NHANES sample, area under the curve = .82, specificity = .78, and sensitivity = .77.

Conclusions
Our data-driven approach identified and validated two items that may be useful as a screening tool for a speedy and accurate assessment of SHSe among children.

Implications
The current study used a rigorous data-driven approach to identify questions that could reliably predict SHSe among children. Using saliva cotinine concentration levels as a gold standard for determining SHSe, our analysis employing elastic net regression identified two questions that served as good classifier for distinguishing children who might be at risk for SHSe. The two items that we validated in the current study can be readily used by clinicians, such as pediatricians, as part of screening procedures to quickly identify whether children might be at risk for SHSe.
Effect of environmental enrichment devices on behavior of individually housed beef heifers
Authors: Bruno Kelsey , DeSocio Elizabeth , White Jason , Wilson Blake K 
Published: November 2020

Abstract
In research settings, certain experimental designs may require cattle to be housed individually. Individual housing of cattle may make the animals more susceptible to boredom and result the development of undesirable behaviors. The objective of this trial was to investigate the effects of different environmental enrichment devices (EED) on the behavior and feed intake of heifers. Twenty mixed-breed single-sourced heifers were used in a completely random design. Heifers were housed individually (3.05 m × 3.66 m) with the ability to have physical contact with adjacent heifers. Heifers were randomly assigned to one of the four EED treatments, including a jolly ball (JLY), a broom head (SRCH), a 182 cm 5-knot rope (RP), or a Pas-a-Fier roller (RLR). Behavior was recorded using 8 h long daily instantaneous scan sampling in 30 min intervals over three periods: 7 d prior to EED addition (PR), 7 d with EED (EDP), and 7 d after removing EED (PST). Standing, laying, eating, drinking, and exploratory behaviors were evaluated. Exploratory behaviors included: interaction with water trough, feed bunk, water pipe, pen gate, pen wall, EED, grooming, or allogrooming. Rumination behavior was also recorded during each observation time. Time standing and standing bouts were greatest for RP (P &lt; 0.05), while JLY and RLR spent the most time lying down (P &lt; 0.05). All heifers spent the majority of observation times lying down, followed by solely standing (P &lt; 0.05). Heifers on the RP treatment interacted the most with their EED, followed by SRCH (P &lt; 0.001). Rumination increased during EDP compared to PR (P &lt; 0.001). These results suggest that a RP suspended from the ceiling in the pen may be used most frequently by individually housed beef heifers.
High Prevalence of Molecular Markers of Plasmodium falciparum Resistance to Sulphadoxine–Pyrimethamine in Parts of Ghana: A Threat to ITPTp-SP?
Authors: Afutu Leslie L , Boampong Johnson N , Quashie Neils B 
Published: November 2020

Abstract

Malaria in pregnancy is a huge public health problem as it is the cause of maternal anaemia, still birth, premature delivery, low birth weight among others. To tackle this problem, WHO recommended the administration, during pregnancy, of intermittent preventive treatment with sulphadoxine–pyrimethamine (IPTp-SP). The introduction of this policy is likely to create SP drug pressure which may lead to the emergence of parasite strains resistant to the drug. This study investigated the prevalence of the molecular markers of SP resistance as pointers to potential failure of IPTp-SP among pregnant women attending antenatal clinic, women at the point of baby delivery and out patients department (OPD) attendees. The study was conducted in health facilities located in parts of Ghana. Prevalence of mutations in dhfr and dhps genes of Plasmodium falciparum was determined using the method described by Duraisingh et al. The outcome of the study indicated the presence of high prevalence of strains of P.falciparum with the resistant alleles of the dhfr or dhps genes in the three categories of participants. There was a high prevalence of triple mutations (IRN) in the dhfr gene of P.falciparum isolates: 71.4% in peripheral blood of antenatal attendees; 74.1% in placenta cord blood of delivering mothers and 71.1% in OPD attendees. Quintuple mutations were only found in 2 (0.5%) isolates from OPD attendees. This observation might have occurred due to the increased use of SP for IPTp among others. There is the need for an interventional measure in order to protect pregnant women and their unborn children.

Lay summary
When pregnant women get infected with the malaria parasites they are exposed to all manner of dangers including pre-term delivery, still birth, maternal anaemia and low birth weight. Taking sulphadoxine–pyrimethamine (SP) at predetermined periods during pregnancy, referred to as ‘intermittent preventive treatment with SP’ (IPTp-SP)’ helps to curtail these problems. However, the frequent taking of these drugs is likely to create SP drug pressure which may lead to the emergence of parasite strains that are not readily killed by the drugs. In order to ascertain this phenomenon and advice stakeholders, this study determined the prevalence of certain ‘materials’ certified as markers of parasite resistance to SP. Alarmingly, more than 5% of all the category of women recruited to participate in this study were found to harbour the parasites that causes malaria. The outcome, also suggest the existence of high levels of strains of the malaria parasite, carrying the materials that make them to become resistant to SP. Policy makers must pay attention to these observations and institute measures to avoid escalation of the situation.
When Obsessive-Compulsive Disorder Mimics Schizophrenia
Authors: Duarte-Mangas Mariana , Bravo Lucilia , Matos-Pires Ana 
Published: November 2020

Abstract
Obsessive-compulsive disorder (OCD) encompasses a broad range of symptoms and is normally considered a heterogeneous disorder. Sometimes, OCD seems to be psychotic in nature, being complex in the differentiation between OCD and schizophrenia. This report describes a female adult patient who was diagnosed in her adolescence with schizophrenia due to her complains of “hearing voices “criticizing her. In response to team request for a second evaluation, she was admitted to the acute inpatient service. After a careful reassessment, the core symptom was recognized as obsession, and her diagnosis was revised to OCD; this allowed for a more direct treatment and management, with cognitive-behavior therapy and high doses of selective serotonin reuptake inhibitors, achieving a sustained clinical improvement over 2 years of follow-up. Currently, she is more functional, participates in social activities, and totally recognizes the egodystonic and intrusive thoughts. This case demonstrates the importance of eliciting psychopathology in greater detail for specific diagnosis and treatment decisions, especially in a complex clinical presentation.
Seasonal patterns of dengue incidence in Thailand across the urban-rural gradient
Authors: Bi Qifang , Cummings Derek AT , Reich Nicholas G. , Keegan Lindsay T. , Kaminsky Joshua , Salje Henrik , Clapham Hannah , Doung-ngern Pawinee , Iamsirithaworn Sopon , Lessler Justin 
Published: November 2020

AbstractIn Southeast Asia, endemic dengue follows strong spatio-temporal patterns with major epidemics occurring every 2-5 years. However, important spatio-temporal variation in seasonal dengue epidemics remains poorly understood. Using 13 years (2003-2015) of dengue surveillance data from 926 districts in Thailand and wavelet analysis, we show that rural epidemics lead urban epidemics within a dengue season, both nationally and within health regions. However, local dengue fade-outs are more likely in rural areas than in urban areas during the off season, suggesting rural areas are not the source of viral dispersion. Simple dynamic models show that stronger seasonal forcing in rural areas could explain the inconsistency between earlier rural epidemics and dengue “over wintering” in urban areas. These results add important nuance to earlier work showing the importance of urban areas in driving multi-annual patterns of dengue incidence in Thailand. Feedback between geographically linked locations with markedly different ecology is key to explaining full disease dynamics across urban-rural gradient.
Pharmacogenomics implementation training improve self-efficacy and competency to drive adoption in clinical practice
Authors: Adesta Fadhli , Mahendra Caroline , Junusmin Kathleen Irena , Selva Rajah Arya Melissa , Goh Sharon , Sani Levana , Chan Alexandre , Irwanto Astrid 
Published: November 2020

ABSTRACTBackgroundAdministration of pharmacogenomics (PGx) testing in clinical practice has been suboptimal, presumably due to lack of PGx education. Here, we aim to evaluate the standpoint of PGx testing among a diverse group of healthcare professionals (HCPs) through conducting surveys before and after training.Materials & MethodsTraining modules were designed to cover 3 key learning objectives and deployed in 5 sections. A pre- and post-training survey questionnaire was used to evaluate participants self-assessments on employing PGx in clinical practice.Results & ConclusionOut of all enrollments, 102 survey responses were collected. Overall, respondents agree on the benefits of PGx testing, but have inadequate self-efficacy and competency in utilizing PGx data. Our results show that training significantly improve these, and even leading to greater anticipation of PGx adoption.