bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sex is an important prognostic factor for glioblastoma but not for nonglioblastoma
Authors: Gittleman Haley , Ostrom Quinn T , Stetson L C , Waite Kristin , Hodges Tiffany R , Wright Christina H , Wright James , Rubin Joshua B , Berens Michael E , Lathia Justin , Connor James R , Kruchko Carol , Sloan Andrew E , Barnholtz-Sloan Jill S 
Published: May 2019

Abstract

Background
Glioblastoma (GBM) is the most common and most malignant glioma. Nonglioblastoma (non-GBM) gliomas (WHO Grades II and III) are invasive and also often fatal. The goal of this study is to determine whether sex differences exist in glioma survival.

Methods
Data were obtained from the National Cancer Database (NCDB) for years 2010 to 2014. GBM (WHO Grade IV; N = 2073) and non-GBM (WHO Grades II and III; N = 2963) were defined using the histology grouping of the Central Brain Tumor Registry of the United States. Non-GBM was divided into oligodendrogliomas/mixed gliomas and astrocytomas. Sex differences in survival were analyzed using Kaplan–Meier and multivariable Cox proportional hazards models adjusted for known prognostic variables.

Results
There was a female survival advantage in patients with GBM both in the unadjusted (P = .048) and adjusted (P = .003) models. Unadjusted, median survival was 20.1 months (95% CI: 18.7-21.3 months) for women and 17.8 months (95% CI: 16.9-18.7 months) for men. Adjusted, median survival was 20.4 months (95% CI: 18.9-21.6 months) for women and 17.5 months (95% CI: 16.7-18.3 months) for men. When stratifying by age group (18-55 vs 56+ years at diagnosis), this female survival advantage appeared only in the older group, adjusting for covariates (P = .017). Women (44.1%) had a higher proportion of methylated MGMT (O6-methylguanine-DNA methyltransferase) than men (38.4%). No sex differences were found for non-GBM.

Conclusions
Using the NCDB data, there was a statistically significant female survival advantage in GBM, but not in non-GBM.
High Yield of Active Tuberculosis Case Finding Among HIV-Infected Patients Using Xpert MTB/RIF Testing
Authors: Kempker Russell R , Chkhartishvili Nikoloz , Kinkladze Inga , Schechter Marcos C , Harrington Kristin , Rukhadze Nino , Dzigua Lela , Tserstvadze Tengiz , del Rio Carlos , Blumberg Henry M , Tukvadze Nestani 
Published: May 2019

Abstract

Objective
Conduct an active case finding study in Tbilisi, Georgia, for pulmonary tuberculosis (TB) among people living with HIV (PLWH).

Methods
Newly diagnosed HIV patients were assessed for symptoms and asked to submit sputum samples for smear microscopy, culture, and molecular diagnostic testing (Xpert MTB/RIF).

Results
Among 276 PLWH, 131 agreed to participate and 103 submitted sputum samples. Most participants were male (70%) and mean age of 43 years. There were high rates of a positive hepatitis C virus (HCV) antibody test (46%) and the median CD4 count was 122 cells/mm3. A total of 15 (11.5%) persons were diagnosed with pulmonary TB, including 1 each with multidrug-resistant and isoniazid-resistant disease. Twelve had a positive culture for Mycobacterium tuberculosis and Xpert TB/RIF assay, and 4 had positive smear microscopy. Patients with pulmonary TB were more likely to use injection drugs (67% vs 36%, P = .02) and have a positive HCV antibody (73% vs 42%, P = .02). The presence and absence of any TB symptom had a sensitivity and negative predictive value for TB of 93% and 98%, respectively.

Conclusion
Our findings highlight the high prevalence of TB among newly diagnosed HIV-infected patients in an area with high rates of drug-resistant TB and the utility of an active case finding strategy for TB diagnosis.
Olatunbosun v State: Safeguarding Children Against Kidnapping in Worship Places
Authors: Akinloye Idowu A , Akinloye Aduragbemi 
Published: May 2019

Abstract
This discussion uses the Nigerian case of Olatunbosun v State to explore the need for Christian churches to take practical and proactive measures to reduce the risk of child kidnapping in their premises used for worship. It observes the increase in the recurrence of child kidnapping in Nigerian churches over the years is of concern because it poses a serious challenge to the victim, the victim's family and the religious organization. It recommends some measures that religious organizations may adapt to reduce the menace and its attendant risks.
PhePEBP family genes regulated by plant hormones and drought are associated with the activation of lateral buds and seedling growth in Phyllostachys edulis
Authors: Zhao Jianwen , Gao Peijun , Li Chunlong , Lin Xinchun , Guo Xiaoqin , Liu Shenkui 
Published: May 2019

Abstract
Development of lateral buds on the underground rhizome in moso bamboo is essentially the early stage of the development of aboveground branching, which is regulated by Phosphatidyl-Ethanolamine Binding Protein (PEBP) family genes, but it is unknown whether the PEBP family genes are involved in the activation and development of lateral buds underground. By scanning the whole-genome sequence of moso bamboo, we identified 25 PhePEBP family genes and amplified their full-length open reading frames (ORFs). A sequence analysis revealed that they are composed of four exons and three introns, except for PheFT10, which contains six exons and five introns. PheFT10 underwent alternative splicing, resulting in at least four transcripts (PheFT10α, PheFT10β, PheFT10γ and PheFT10δ). Although PhePEBP genes are generally expressed at low levels and show dramatically organ-specific expressions, the transcription levels of most PhePEBP genes, including the transcripts of PheFT10, change with plant age. Together with the observation that the expression of PhePEBP family genes can be regulated by plant hormones and drought, our data suggest that PhePEBP family genes might be involved in the activation of lateral buds and seedling growth. Particularly, PheFT9, PheTFL2 and PheTFL8 may play vital roles during the activation of dormant buds based on the analysis of amino acid substitution and expression profile. These findings provide insights for in-depth exploration of the biological functions of the PhePEBP family genes in regulating the activation of dormant bud and the development of seedling in moso bamboo.
Assessment of chemotherapy-induced organ damage with 68Ga-labeled duramycin
Authors: Rix Anne , Drude Natascha Ingrid , Mrugalla Anna , Baskaya Ferhan , Pak Koon Yan , Gray Brian , Kaiser Hans-Jürgen , Tolba René Hany , Fiegle Eva , Lederle Wiltrud , Mottaghy Felix Manuel , Kiessling Fabian 
Published: May 2019

AbstractCompared to standard toxicological techniques in preclinical toxicity studies, non-invasive imaging of organ toxicity enables fast and longitudinal investigation of the whole animal. Therefore, we set out to evaluate [68Ga]Ga-NODAGA-duramycin as a positron emission tomography (PET)-tracer of cell death for detecting chemotherapy-induced organ toxicity.MethodsNODAGA-duramycin was radiolabeled with 68Ga, and quality control was done by thin layer chromatography and high performance liquid chromatography. Tracer specificity was determined in vitro by performing competitive binding experiments on ethanol treated cells. To optimize the timing of the PET/CT-based tracer evaluation, kinetic studies were performed in untreated and cisplatin-treated (20 mg/kg BW, intraperitoneal (i.p.)) BALB/cAnNRj mice. Organ uptake was analyzed in doxorubicin (4 mg/kg BW, i.p.)-, busulfan (18.8 mg/kg KG, i.p.)-, and cisplatin-treated (20 mg/kg BW, i.p.) mice, and in untreated control mice 2 hours after intravenous injection of 5–10 MBq [68Ga]Ga-NODAGA-duramycin. For immunofluorescence validation, tissue sections were stained with anti-active caspase-3 antibody. Blood and serum samples were collected to determine platelet count, aspartate transaminase, alanine transaminase, urea, creatinine, and creatine kinase values.ResultsIn vitro experiments confirmed specific binding of [68Ga]Ga-NODAGA-duramycin to dying cells. The biodistribution analysis revealed a blood half-life of 10–17 minutes and a predominantly urinary excretion of the radiotracer. Doxorubicin-, busulfan-, and cisplatin-induced organ toxicities were detected successfully using [68Ga]Ga-NODAGA-duramycin PET/CT and confirmed by immunohistochemistry as well as blood parameter analysis. Busulfan-related spleno-, cardio-, and pneumotoxicity as well as cisplatin-induced cardio- and pneumotoxicity were detected even earlier by [68Ga]Ga-NODAGA-duramycin PET/CT than by blood parameters and histological stainings. In livers and kidneys, differences between treated and untreated animals tended to occur in PET/CT at later time points than in histology due to the relatively high background in these organs. However, trends over time were comparable.Conclusion[68Ga]Ga-NODAGA-duramycin PET/CT was successfully applied to non-invasively detect chemotherapy-induced organ toxicity with high sensitivity in preclinical studies. It even depicted some toxic effects prior to immunohistochemistry and blood parameter analysis and represents a promising alternative or complementary method to standard toxicological analyses. Furthermore, the tracer has a high translational potential and may provide a valuable link between preclinical and clinical research.
The Emerging Gait Dysfunction Phenotype in Idiopathic Parkinson’s Disease
Authors: Skidmore Frank M. , Monroe William S , Hurt Christopher , Nicholas Anthony P , Gerstenecker Adam , Anthony Thomas , Jololian Leon , Cutter Gary , Bashir Adil , Denny Thomas , Standaert David , Disbrow Elizabeth A 
Published: May 2019

ABSTRACTObjectiveSeverity of motor symptoms in Parkinson’s disease (PD), and rate of change of these symptoms, suggests the existence of disease subgroups. One important PD subgroup is defined by postural instability and gait dysfunction (PIGD), which is associated with disability, lower quality of life, and cognitive deterioration. In this study, we evaluate what clinical factors at baseline are associated with early development of postural instability in PD.MethodsData was downloaded from the Parkinson’s Progressive Markers Initiative (PPMI). Several clinical features predict development of postural instability. We provisionally term the associated phenotype the emerging gait disorder (eGD) phenotype. We evaluate validity of the phenotype in two held-out populations.ResultsIndividuals with the proposed eGD phenotype have a significantly higher risk of developing postural instability in both validation sets (p < 0.00001 in both sets). The proposed eGD phenotype occurred before development of postural instability (HY stage ≥ 3) in 289 of 301 paired comparisons (Fischer Exact Test, p < 0.000001), with a median progression time from development of eGD phenotype to postural instability of 972 days. Individuals with the proposed eGD phenotype at baseline had more rapid cognitive decline as measured by the Montreal Cognitive Assessment (p = 0.002) and Hopkins Verbal Learning Test (Total Recall, p = 0.008).InterpretationWe describe a clinical phenotype, detectable at baseline in a subset of individuals with PD, that is associated with accelerated development of postural instability. Within the sample, development of the eGD phenotype reliably precedes development of disability, and is a harbinger of more rapid cognitive progression.
Multiple independent origins of apicomplexan-like parasites
Authors: Mathur Varsha , Kolisko Martin , Hehenberger Elisabeth , Irwin Nicholas AT , Leander Brian S. , Kristmundsson Árni , Freeman Mark A , Keeling Patrick J 
Published: May 2019

AbstractApicomplexans are a diverse group of globally important parasites, that include pathogens like Plasmodium, the causative agent of malaria. Despite their current obligate parasitic nature, apicomplexans evolved from photosynthetic algae and retain a remnant plastid (chloroplast). Such a complex evolutionary transition was unexpected, but here we show that it occurred at least three times independently. Using single-cell genomics and transcriptomics from diverse uncultivated parasites, we find that two genera previously classified within the Apicomplexa, Piridium and Platyproteum, form separately branching lineages in phylogenomic analyses. Both retain cryptic plastids with genomic and metabolic features convergent with apicomplexans. These findings suggest a predilection in this lineage for both the loss of photosynthesis and the transition to a morphologically similar parasitic lifestyle, resulting in multiple lineages of highly convergent animal parasites.
Survival status and predictors of mortality among Breast Cancer patients in Adult Oncology Unit at Black Lion Specialized Hospital, Addis Ababa, Ethiopia, 2018
Authors: Areri Habtamu Abera , Shibabaw Wondimeneh , Mulugeta Tefera , Asmare Yared , Yirga Tadesse 
Published: May 2019

AbstractIntroductionBreast cancer is a foremost cause of death worldwide, ranks fifth among causes of death from all types of cancers; this is the most common cause of cancer death in women among both developing and developed countries. Breast cancer ranks first among most frequent cancers in women of Ethiopia. In spite of the high incidence, mortality rate, and survival status among breast cancer patients was not determined in Ethiopia.ObjectiveThe main aim of the study is to assess the survival status and predictor the mortality among Breast Cancer patients in Adult Oncology Unit at Black Lion Specialized Hospital in 2018.MethodsAn institution based retrospective follow up study was conducted in Adult Oncology Unit at Black Lion Specialized Hospital. All cases of breast cancer registered from 1stJanuary 2012 to 31thDecember,2014 were followed for the six-year survival (until 31thDecember, 2017). Kaplan-Meier survival curve together with log rank test was deployed to test for variations in the survival among predictor variables. Cox regression was used at 5% level of significance to determine the net effect of each independent variable on time to death of breast cancer clients.ResultsThe results indicate that the incidence rate of mortality was 9.8 per 100 person/ years (95% CI: 8.49-11.47).The overall median survival time was 56.5(95% CI (53.46 - 60.83)) months. The overall estimated survival rate was recorded 27% (95% CI, 17.09 to 36.67 %) at 72 months of follow up, whereas at odd years (1, 3, and 5 years) were, 97.2%, 80.8%, and 46.2% respectively. Predictors of mortality were assessed at clinical stage (III&IV),(AHR =1.86), poorly differentiated histology (AHR: 3.1) & positive lymph node status (AHR:3.13),Whereas adjuvant hormone therapy (AHR: 0.67) and chemotherapy (AHR:0.72) were protective.ConclusionThe overall probability of survival in Ethiopia was inferior when compared with other high and middle-income countries. Predictors of mortality were at advanced clinical stage, poorly differentiated histology grade, surgical margin involvement and positive lymph node status. In contrary, adjuvant hormone therapy, modified radical mastectomy and chemotherapy were protective factors. Hence, special emphasis could be given to early screening, stage diagnosis and initiation of treatment.
Acid and inflammatory sensitisation of naked mole-rat colonic afferent nerves
Authors: Hockley James R.F. , Barker Katie H. , Taylor Toni S. , Callejo Gerard , Husson Zoe M. , Bulmer David C. , Smith Ewan St. J. 
Published: May 2019

AbstractAcid sensing in the gastrointestinal tract is required for gut homeostasis and the detection of tissue acidosis caused by ischaemia, inflammation and infection. In the colorectum, activation of colonic afferents by low pH contributes to visceral hypersensitivity and abdominal pain in human disease including during inflammatory bowel disease. The naked mole-rat (Heterocephalus glaber; NMR) shows no pain-related behaviour to subcutaneous acid injection and cutaneous afferents are insensitive to acid, an adaptation thought to be a consequence of the subterranean, likely hypercapnic, environment in which it lives. As such we sought to investigate NMR interoception within the gastrointestinal tract and how this differed from the mouse (Mus Musculus). Here we show the presence of calcitonin gene regulated peptide (CGRP) expressing extrinsic nerve fibres innervating both mesenteric blood vessels and the myenteric plexi of the smooth muscle layers of the NMR colorectum. Usingex vivocolonic-nerve electrophysiological recordings we show differential sensitivity of NMR, compared to mouse, colonic afferents to acid and the prototypic inflammatory mediator bradykinin, but not direct mechanical stimuli. In NMR, but not mouse, we observed mechanical hypersensitivity to acid, whilst both species sensitised to bradykinin. Collectively, these findings suggest that NMR colonic afferents are capable of detecting acidic stimuli, however, their intracellular coupling to downstream molecular effectors of neuronal excitability and mechanotransduction likely differs between species.
Three-gene PCR and high-resolution melting analysis for differentiating vertebrate species mitochondrial DNA for forensic and biodiversity research pipelines
Authors: Ouso Daniel O. , Otiende Moses Y. , Jeneby Maamun , Oundo Joseph W. , Bargul Joel L. , Miller Scott , Wambua Lillian , Villinger Jandouwe 
Published: May 2019

AbstractReliable molecular identification of vertebrate species from morphologically unidentifiable tissue is critical for the prosecution of illegally-traded wildlife products, conservation-based biodiversity research, and identification of blood-meal hosts of hematophagous invertebrates. However, forensic identification of vertebrate tissue relies on the sequencing of mitochondrial cytochrome oxidase I (COI) ‘barcode’ genes, which remains costly for purposes of screening large numbers of unknown samples during routine surveillance. Here, we adopted a rapid, low-cost approach to differentiate 10 domestic and 24 wildlife species that are common in the East African illegal wildlife products trade based on their unique high-resolution melting profiles from COI, cytochrome b, and 16S ribosomal RNA gene PCR products. Using the approach, we identified (i) giraffe among covertly sampled meat from Kenyan butcheries, and (ii) forest elephant mitochondrial sequences among savannah elephant reference samples. This approach is being adopted for high-throughput pre-screening of potential bushmeat samples in East African forensic science pipelines.
The nucleosome acidic patch directly interacts with subunits of the Paf1 and FACT complexes and controls chromatin architecture in vivo
Authors: Cucinotta Christine E. , Hildreth A. Elizabeth , McShane Brendan M. , Shirra Margaret K. , Arndt Karen M. 
Published: May 2019

AbstractThe nucleosome core regulates DNA-templated processes through the highly conserved nucleosome acidic patch. While structural and biochemical studies have shown that the acidic patch controls chromatin factor binding and activity, few studies have elucidated its functions in vivo. We employed site-specific crosslinking to identify proteins that directly bind the acidic patch in Saccharomyces cerevisiae and demonstrated crosslinking of histone H2A to Paf1 complex subunit Rtf1 and FACT subunit Spt16. Rtf1 bound to nucleosomes through its histone modification domain, supporting its role as a cofactor in H2B K123 ubiquitylation. An acidic patch mutant showed defects in nucleosome positioning and occupancy genome-wide. Our results provide new information on the chromatin engagement of two central players in transcription elongation and emphasize the importance of the nucleosome core as a hub for proteins that regulate chromatin during transcription.
Multiplexed imaging of immune cells in staged multiple sclerosis lesions by mass cytometry
Authors: Ramaglia Valeria , Sheikh-Mohamed Salma , Legg Karen , Rojas Olga L , Zandee Stephanie , Fu Fred , Ornatsky Olga , Swanson Eric C , Prat Alexandre , McKee Trevor D , Gommerman Jennifer L 
Published: May 2019

ABSTRACTMultiple Sclerosis (MS) is characterized by demyelinated and inflammatory lesions in the brain and spinal cord. Lesions contain immune cells with variable phenotypes and functions. Here we use imaging mass cytometry (IMC) to enable the simultaneous imaging of 15+ proteins within 11 staged MS lesions. Using this approach, we demonstrated that the majority of demyelinating macrophage-like cells in active lesions were derived from the resident microglial pool. Although CD8+ T cells predominantly infiltrated the lesions, CD4+ T cells were also abundant but localized closer to blood vessels. B cells with a predominant switched memory phenotype were enriched across all lesion stages and were found to preferentially infiltrate the tissue as compared to unswitched B cells which localized to the vasculature. We propose that IMC will enable a comprehensive analysis of single-cell phenotypes, their functional states and cell-cell interactions in relation to lesion morphometry and demyelinating activity in the MS brain.
Simultaneous 3D super-resolution fluorescence microscopy and atomic force microscopy: combined SIM and AFM platform for cell imaging
Authors: Gómez-Varela Ana I. , Stamov Dimitar R. , Miranda Adelaide , Alves Rosana , Barata-Antunes Cláudia , Dambournet Daphné , Drubin David G. , Paiva Sandra , De Beule Pieter A. A. 
Published: May 2019

AbstractCorrelating data from different microscopy techniques holds the potential to discover new facets of signaling events in cellular biology. Here we report for the first time a hardware set-up capable of achieving simultaneous imaging of spatially correlated super-resolution fluorescence microscopy and atomic force microscopy, a feat only obtained until now by fluorescence microscopy set-ups with spatial resolution restricted to the Abbe resolution limit. We hereby remove the need to perform independent measurement and subsequent data averaging required to eliminate cell-to-cell variation in observed signals. We detail system integration, demonstrate system performance and report imaging of sub-resolution fluorescent beads and genome-engineered human bone osteosarcoma epithelial cells.