jimnoneill/paper-to-field-training huggingface dataset:
CHRONIC LYMPHOCYTIC LEUKEMIA INVOLVEMENT OF CENTRAL NERVOUS SYSTEM: A SINGLE CENTRE EXPERIENCE

Field: Medicine (Health Sciences)

Introduction: Chronic lymphocytic leukemia (CLL) involvement of central nervous system (CNS) is reported to be rare, mainly due to only occasional appear of predominantly non-specific neurological symptoms. Neurologic complications arising from direct leukemic involvement of CNS is stated in only 1% of patients (pts) with CLL. There is no treatment consensus with similar results of intrathecal chemotherapy or whole-brain irradiation, but some more recent studies reported more encouraging data with application of immunochemotherapy or tyrosine kinase inhibitor, ibrutinib. CLL with CNS involvement is related with poorer outcome, especially for pts with unfavorable cytogenetic (17p deletion). Methods: We presented a small series of four pts that were diagnosed and treated in our Institution. All pts met the International Workshop on CLL diagnostic criteria (2008). Diagnosis of CNS involvement was established via neuroimaging methods such as MRI, as well as cerebrospinal fluid (CSF) cytology, and CSF multiparameter flow cytometry immynophenotyping method (CSF FCM). Results: All pts were men with average age of 55.25 years (yrs). On CNS onset, all had disseminated disease and 17p deletion was registered in one case. Average latency period from CLL to CNS onset was 2.91 yrs. We registered heterogeneous neurological symptoms on CNS onset, including bradypsyhia, headaches, nausea, vomiting, dysphasia, repeated unconsciousness, urinary incontinence, dyslexia, lack of fine motor control, diplopia and bilateral eyelid swelling. Diagnostics included positive CSF cytology in three cases, CSF FCM was performed in all of our cases. MRI scan was performed in all cases and was conclusive in three (75%) cases. On CLL onset, two pts were treated with systemic chemotherapy, FC (fludarabine, cyclophosphamide) in one case and CHOP (cyclophosphamide, doxorubicine, vincristine, prednisolone) in other, third was initially treated with corticosteroid therapy due to immunological thrombocytopenia and fourth was on “watch and wait” policy, due to comorbidities. Two of our pts were treatment naïve on CNS onset. When CLL in CNS was diagnosed, systemic chemotherapy was applied in all cases. First patient received high-dose methotrexate with intrathecal therapies, second R(rituximab)-FC, and two received DHAP regimen (dexametasone, high-dose cytarabine, cisplatin) in two cases. Average and median OS from CNS onset was 4 and 3.5 months, respectively, with lethal outcome in 75% of cases in our follow-up. Conclusions: CLL in CNS is still rarely diagnosed, primarily due to the presence of heterogeneous, non-specific neurological symptoms, or their absence. The most effective diagnostics includes MRI, CSF-FCM, and if it is possible PCR detection of CLL cells in CSF. Our results confirm the poor therapeutic outcome and short survival in our group of pts. Keywords: chronic lymphocytic leukemia (CLL); flow cytometry; immunochemotherapy.
DESIGN OF DESIGN ORIENTED CURRICULUMS: WHAT IS THE OPTIMAL BALANCE?

Field: Arts and Humanities (Social Sciences)

Appears in: ICERI2016 Proceedings Publication year: 2016Pages: 5096-5106ISBN: 978-84-617-5895-1ISSN: 2340-1095doi: 10.21125/iceri.2016.2217Conference name: 9th annual International Conference of Education, Research and InnovationDates: 14-16 November, 2016Location: Seville, Spain
Nonlinear beam self-maintaining effect in graded-index multimode fiber

Field: Computer Science (Physical Sciences)

Multimode fiber systems are desirable for industrial and scientific applications. As an interesting effect for the laser beam propagation in a multimode fiber, nonlinear Kerr beam cleanup has attracted considerable research interest due to the spatial beam compressing. However, its physical mechanisms, especially the influences of input conditions on its performances, remain unclear. Here, we report a new self-organized regime for the multimode beam propagation in a graded-index multimode fiber: when the input laser has a dominant mode in which most of the laser energy is concentrated, the beam profile can be maintaining in a well-defined structure similar to the input dominant mode in nonlinear regime, while it will evolve to an irregular pattern in linear regime. The existence and universality of this nonlinear beam self-maintaining effect have been verified by the experimental and numerical data. Our results also provide evidence that nonlinear Kerr effects can be the driving mechanism and nonlinear Kerr beam cleanup is a specific case of this effect. Further research into this spatial beam shaping effect may provide a new perspective to understand other multimode fiber nonlinearities.
Jackknife resampling for precision measurement of direct gene flow estimates

Field: Agricultural and Biological Sciences (Life Sciences)

AbstractGene flow from outside pollen sources reduces the expected genetic gain of seed orchards, and has been quantified by genotyping seed samples from crop years to determine the proportion of seed sired by outside sources. Random bulk seed sampling and microsatellite genotyping allows for fast, unbiased identification of orchard contamination rates. Bulk seed sampling has been employed in multiple studies of seed orchard gene flow, but a method of determining precision of gene flow estimates from this sampling method has yet to be described. In this study, we used jackknife resampling to generate random samples of migrant and within-population genotypes obtained from an empirical sample of Douglas-fir (Pseudotsuga menziesii [Mirb.] Franco) genotypes of five microsatellite loci. We generated samples of 50, 100, 150, 200, and 250 genotyped individuals from a sample of 400 seeds, with genotypes corresponding to low (6%), moderate (14%), or high (56%) pollen contamination levels. The mean gene flow estimate and confidence interval were calculated for each sample size and gene flow scenario to determine the precision of gene flow estimates obtained from each sample size in each contaminant gene flow scenario. Genotyping 150 individuals was sufficient to produce gene flow estimates with calculated confidence interval values below ± 1%, indicating that 150 genotyped individuals were sufficient for precise gene flow estimation in this population. This resampling method will enable precise and unbiased estimation of gene flow into seed orchards for future monitoring of gene flow, to allow better management of seed orchard genetic resources.Keywords: gene flowresamplingseed orchardspollen contaminationpedigree reconstruction AcknowledgmentsWe thank C. Cook and A. Van Niejenhuis (Western Forest Products Inc.) for providing orchard seed and parental bud tissue. Generation of resampled ID's was carried out in R by Dr Jaroslav Klapste's, whose assistance is greatly appreciated.FundingFunds from the Johnson's Family Forest Biotechnology Endowment, British Columbia Forest Investment Account Forest Genetic Conservation and Management program, Natural Sciences and Engineering Research Council of Canada – Discovery and Industry Research Chair grants were provided to Yousry A El-Kassaby, and a Natural Sciences and Engineering Research Council Canadian Graduate Scholarship supported research for Tony Kess.Additional informationFundingFunding: Funds from the Johnson's Family Forest Biotechnology Endowment, British Columbia Forest Investment Account Forest Genetic Conservation and Management program, Natural Sciences and Engineering Research Council of Canada – Discovery and Industry Research Chair grants were provided to Yousry A El-Kassaby, and a Natural Sciences and Engineering Research Council Canadian Graduate Scholarship supported research for Tony Kess.
Core-shell electrospun fibers for delivery of hydrophilic drugs

Field: Pharmacology, Toxicology and Pharmaceutics (Life Sciences)

The current mode of insulin delivery for diabetic patients is through subcutaneous injection, which is invasive, inconvenient and causes infections. Although oral delivery of insulin may allow better patient compliance due to ease of administration, it is very challenging due to low bioavailability as insulin will degrade in the acidic stomach environment. Much research has been done on alternative methods to deliver insulin which are non-invasive, one of which is through buccal delivery. Core-shell nanofibers spun using a co-axial electrospinning technique have been found to have the ability to control the drug release. In this project, electrospun core-shell nanofibers were fabricated using a co-axial electrospinning technique. The nanofibers consist of a core loaded with insulin and a shell composed of a blend of pH-responsive polymers (i.e. Eudragit) which can potentially control the rate of drug release. Eventually, the core-shell nanofibers can be placed on the buccal tissue and may deliver the insulin through the buccal mucosa as the nanofibers dissolve in the saliva. Optimization and characterisation of the electrospun core-shell nanofibers were done using confocal microscopy and scanning electron microscopy. The drug release behaviours of monolithic and core-shell nanofibers were studied by dissolving them in simulated saliva and measuring the amount of insulin released. The drug release results show that the core-shell nanofibers dissolved over an extended period of time and were able to maintain a sustained release, whereas the monolithic nanofibers dissolved instantly to give a burst release. This demonstrates the important role that the Eudragit shell plays in the ability of the core-shell nanofibers to control drug release. However, the measured drug encapsulation of the core-shell nanofibers was very low. Overall, the core-shell nanofibers have the potential to control the release of the insulin but further optimization and investigation to need to be done to improve the drug release.
Power-rail ESD clamp circuit with embedded-trigger SCR device in a 65-nm CMOS process

Field: Engineering (Physical Sciences)

SCR is the preferred ESD protection device in nanoscale CMOS technologies due to the better area efficiency compared the BIGFET, virtually no leakage current and smaller capacitance. The main drawback of the SCR is the slow turn-on speed, which is solved by adding dummy gates to block the STI formations inside the SCR structure. This work demonstrates that the dummy gate inside the SCR can be effectively used as an embedded trigger transistor, eliminating the need of an external trigger transistor in the ESD protection circuit and so further reducing silicon area and standby leakage current.
inical and radiological features of the late-onset methylmalonic aciduria: a review of three cases

Field: Medicine (Health Sciences)

abstractjective To study the clinical and radiological features of the patients with late-onset methylmalonic aciduria ( MMA). Methods Two men and one woman with MMA were screened and confirmed by urinary organic acid analysis with gas chromatograph/mass spectrometer (GC/MS) at their 26, 18 and 34 years old, respectively. Their clinical features, laboratory findings, radiological manifestations, treatment and outcome were reviewed. Results The clinical features of 3 patients were varied with neurological abnormalities. Case 1 had periodic enuresis for 16 months, progressive dementia and movement disorder for 3 months. Physical examination showed an apparent cognitive decline with psychiatric symptoms. Dysarthria, bilateral weakness and pyramidal signs, rigidity and mild tremor of limbs were observed. Case 2 had a progressive memory deterioration, learning difficulty, walking unstably and decreased vision when he was 13 years old, and a general seizure at an age of 16 years. Diffused abnormalities of EEG and rnild renal defects were found in the above two patients. General white matter hyperintensity and cerebral atrophy on T2-weighted MR images were evident. Additionally, these two patients had hyperhomocystinemia and carnitine deficiency. Case 3 had complained about walking unstably and fatigue over 2 months. Reduced facial movements, deep sensation loss and muscle weakness in lower extremities, marked rigidity and diminished tendon reflexes were detected. Megaloblastic anemia and cobalamin deficiency were found. MRJ performed revealed bilateral symmetric areas having high density involving the globi pallidi, posterior limbs of internal capsule and the cerebral peduncles. Remarkable elevations of urinary methylmalonic and methylcitric acid were confirmed in all 3 patients. After vitamin B12 supplementation, significant improvement was observed. Conclusion Three cases with vitamin BI2 responsive type of late-onset MMA were reported. Two patients were combined with hyperhomocystinemia and the other had only isolated MMA. There might remain prominent differences among MMA subgroups in clinical presentations and neuroradiologic findings. Vitamin
B12 might be very effective to improve the prognosis of the patients. MMA should be considered as a differential diagnosis for the etiological investigation of adult cerebral metabolic or degenerative diseases.
Oxidative stress-mediated senescence in mesenchymal progenitor cells causes the loss of their fibro/adipogenic potential and abrogates myoblast fusion

Field: Biochemistry, Genetics and Molecular Biology (Life Sciences)

Sarcopenia is the age-related loss of skeletal muscle mass and function. Skeletal muscle comprises diverse progenitor cells, including mesenchymal progenitor cells (MPCs), which normally support myogenic cell function but cause a decline in skeletal muscle function after differentiating into fibrous/adipose tissue. Cellular senescence is a form of persistent cell cycle arrest caused by cellular stress, including oxidative stress, and is accompanied by the acquisition of senescence-associated secretory phenotype (SASP). Here, we found γH2AX+ senescent cells appeared in the interstitium in skeletal muscle, corresponding in position to that of MPCs. H2O2 mediated oxidative stress in 2G11 cells, a rat MPC clone previously established in our laboratory, successfully induced senescence, as shown by the upregulation of p21 and SASP factors, including IL-6. The senescent 2G11 cells lost their fibro/adipogenic potential, but, intriguingly, coculture of myoblasts with senescent 2G11 cells abrogated the myotube formation, which coincided with the downregulation of myomaker, a muscle-specific protein involved in myogenic cell fusion; however, forced expression of myomaker could not rescue this abrogation. These results suggest that senescent MPCs in aged rat skeletal muscle lose their fibro/adipogenic potential, but differ completely from undifferentiated progenitor cells in that senescent MPCs suppress myoblast fusion and thereby potentially accelerate sarcopenia.
A pilot presurgical study evaluating anti-PD-L1 durvalumab (durva) plus anti-CTLA-4 tremelimumab (treme) in patients (pts) with high-risk muscle-invasive bladder carcinoma (MIBC) who are ineligible for cisplatin-based neoadjuvant chemotherapy (NAC).

Field: Medicine (Health Sciences)

4551 Background: In MIBC pts, especially in those with high risk features including lymphovascular invasion, hydronephrosis, T3b disease, or variant histology, cisplatin-based NAC followed by cystectomy improves overall survival as compared with cystectomy alone. However, it is estimated that over 50% of pts with MIBC are ineligible for cisplatin-containing therapy. Therefore, we propose this pre-surgical trial with durva + treme for this population of pts. Methods: This is a single-arm, pre-surgical clinical trial with durva + treme in pts with localized, high-risk MIBC (cT2-T4a) who are ineligible for cisplatin-based NAC due to decreased renal function, neuropathy, hearing loss, or heart failure; or refuse cisplatin-based NAC (NCT02812420). Each patient receives durva (1500 mg) plus treme (75 mg) on weeks 1 and 5. Pts then undergo surgery at week 9-11. Pre- and post-treatment blood and tumor samples are collected for correlative biological analyses. Results: Twenty eight of 35 pts have been enrolled on this trial. Twenty-one pts have completed cystectomy as of 11/16/19. Of these 21 pts, 9 (43%) had pathologically complete response (pCR) and two (10%) had pathologic T1N0 (pT1) disease (≤pT1N0 rate = 52%). Fourteen of 21 (67%) had down-staging of disease. Of note, 10 of these 21 pts had 3-D mass (T3) on exam under anesthesia or clinical T4a disease; 5 of these 10 pts (50%) had pCR and one (10%) had pT1 disease (≤pT1N0 rate = 60%). Only 5 of 28 (17%) pts developed grade 3 immune related toxicity including hepatitis and amylase/lipase elevation, and two (7%) resulted in surgery delay for > 30 days. Immune profiling with CyTOF analysis of baseline peripheral blood indicates that pts with pCR have significantly lower frequency of a Th2 subset as compared to pts with up-staging of disease. In addition, gene expression profiling analysis of baseline tumor tissues demonstrates a significantly less immunosuppressive microenvironment in pts with pCR as compared to pts with up-staging of disease. Conclusions: Our data indicate that durva plus treme is an effective and safe neoadjuvant therapy for pts with MIBC ineligible for cisplatin-based therapy. Therefore, neoadjuvant therapy with durva + treme and a number of potential biomarkers warrant testing in a larger phase 3 trial. Clinical trial information: NCT 02812420.
The Research Progress of miRNA in Plant Somatic Embryogenesis

Field: Agricultural and Biological Sciences (Life Sciences)

The action mechanism of plant miRNA was introduced,then,the research progress of miRNAs in Larix ssp,maize and longan somatic embryogenesis was elaborated. Given the intense research of miRNA,the functional verification of miRNA,the regulation among different miRNA and the regulation of target genes should become the important research direction. Therefore,it is important to summarize the current status and development trend of miRNAs in plant somatic embryogenesis.
Duplicated Sequence Motif in the Long Terminal Repeat of Maedi-Visna Virus Extends Cell Tropism and Is Associated with Neurovirulence

Field: Biochemistry, Genetics and Molecular Biology (Life Sciences)

ABSTRACT Maedi-visna virus (MVV) is a lentivirus of sheep causing chronic inflammatory disease of the lungs (maedi) and the nervous system (visna). We have previously shown that a duplicated sequence in the long terminal repeat (LTR) of MVV is a determinant of cell tropism. Here, we demonstrate that deletion of a CAAAT sequence from either one of the repeats resulted in poor virus growth in sheep choroid plexus cells. A duplication in the LTR encompassing the CAAAT sequence was found in four neurological field cases that were sequenced, but no duplication was present in the LTRs from seven maedi cases; one maedi isolate was mixed. These results indicate that the duplication in the LTR is associated with neurovirulence.
High throughput screening for small-molecule compounds that induce host defense peptide expression

Field: Pharmacology, Toxicology and Pharmaceutics (Life Sciences)

Host defense peptides (HDPs) are widely expressed in virtually all types of living organisms. With both antimicrobial and immunomodulatory activities, HDPs are a critical component in the innate immune system. The compounds with the ability to induce endogenous HDPs have potential to be developed as alternatives to antibiotics for use in humans and animals. However, the regulation of HDP gene expression is species- and cell type-specific. To identify HDP inducers for poultry and swine applications, we developed two high throughput screening (HTS) systems by employing stable luciferase reporter cell lines under the control of representative chicken and porcine HDP gene promoters, respectively. After HTS screening of a library of epigenetic compounds and two libraries of natural product, a number of hits were identified. The HDP-inducing activities of these hits was further validated and compared in different cell types. A top hit was also confirmed to be effective in augmenting HDP gene expression in the intestinal tract of chickens by oral gavage. Collectively, we have developed two HTS assays to allow identifying HDP inducers. Newly discovered HDP-inducing small-molecule compounds are promising candidates for further development as alternatives to in-feed antibiotics for applications in chickens, pigs, and possibility other animal species.
Prognostic factors of long-term outcomes after primary chemo-radiotherapy in non-metastatic anal squamous cell carcinoma: An international bicentric cohort.

Field: Medicine (Health Sciences)

e15501 Background: Anal squamous cell carcinoma (ASCC) is a rare malignancy with a rising incidence associated with Human papillomavirus (HPV) infection. Locally-advanced disease is associated with a 30% rate of treatment failure after standard chemoradiotherapy (CRT). We aimed to elucidate prognostic factors for ASCC after curative CRT. Methods: A retrospective multicenter study of 176 consecutive patients with ASCC having completed CRT treated between 2010 and 2017 at 2 centers. Complete response (CR), disease-free survival (DFS) and overall survival (OS) were analyzed by Kaplan–Meier estimates with log-rank tests. The hierarchical clustering on principal components (HCPC) method was employed in an unsupervised and multivariate approach. Results: CR rate was 68% and was predictive of DFS (p < 0.0001) and OS (p < 0.0001), where non-CR cases were associated shorter DFS (HR = 16.5, 95% CI 8.19-33.21) and OS (HR = 8.42, 95% CI 3.77–18.81) in univariate analysis. Median follow-up was 38 months, with 3-year DFS of 71%. Prognostic factors for DFS were cT1-T2 (p = 0.0001), N0 (p = 0.03), HIV-positive (p = 0.04), HIV-HPV coinfection (p = 0.02), and well-differentiated tumors (p = 0.03). Three-year OS was 81.6%. Female sex (p = 0.05), cT1-T2 (p = 0.019), and well-differentiated tumors (p = 0.003) were associated with better OS. This unsupervised analysis demonstrates clear segregation, identifying that poor prognosis clusters associated with shorter DFS (HR = 1.66, 95% CI = 1.21–2.27, p = 0.0012) were enriched with locally-advanced disease, anal canal location, HPV-HIV coinfection, and non-CR. Conclusions: In conclusion, our results reinforce the prognostic value of T stage, N stage, sex, differentiation status, tumor location, and HIV-HPV coinfection in ASCC after CRT.
Pathological analysis and clinical significance of the 640 cases of cervical biopsy

Field: Medicine (Health Sciences)

Objective To investigate the clinical significance of colposcopy in diagnosis of cervical lesions.Methods Collected 640 cases of cervical lesions and made cervical tissue biopsy,and then retrospectively analyzed the pathology results.Results There were 506 cases with chronic cervicitis in 640 cases who was examined by colposcopy,13 cases with normal cervical,48 cases with CIN Ⅰ,26 cases with CIN Ⅱ,8 cases with CIN Ⅲ,9 cases with cervical cancer,and 30 cases with cervical acuteness wet wart.Conclusion Cervical biopsy with colposcope can early discover the pre-cancerous cervical tissue,has sure significance for the prevention and cure of cervical cancer.