bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protease inhibitors stimulate hematopoiesis and decrease apoptosis and ICE expression in CD34+ cells
Authors: Sloand Elaine M. , Maciejewski Jaroslaw , Kumar Princy , Kim Sonnie , Chaudhuri Aniruddho , Young Neal 
Published: October 2019

AbstractHighly active retroviral therapy has been associated with a decline in the frequency of cytopenia in patients with human immunodeficiency virus (HIV) infection. This may result from lower hematologic toxicity of newer antiviral drugs and their increased efficacy against HIV-1. Protease inhibitors, in addition to their effects on HIV replication, appear to affect various cellular functions. Recently, it was reported that ritonavir inhibited caspase-1 expression in normal CD4+ cells. It was hypothesized that protease inhibitors may improve hematopoietic function owing to their direct effects on the bone marrow progenitor cells. When ritonavir was added to methylcellulose cultures of bone marrow cells from HIV-infected patients and normal controls, colony formation increased 2.4-fold (n = 5) in control cultures and 4-fold (n = 5) in cultures of cells from HIV-infected patients. In the presence of ritonavir, cultures of CD34+ cells showed markedly decreased apoptosis in comparison with untreated cultures (45% decrease in apoptotic cell number; n = 6). A synthetic inhibitor of caspase 1 (Ac-Tyr-Val-Ala-Asp-aldehyde [single-letter amino acid codes]), which inhibits activation of several caspases including CPP32 and interleukin 1β–converting enzyme (ICE or caspase 1), also decreased the rate of apoptosis and enhanced colony formation by progenitor cells derived from HIV-infected patients (3-fold; n = 5). In ritonavir-treated samples derived from HIV-infected individuals, the number of cells expressing ICE also decreased. In conclusion, HIV protease inhibitors may, by blocking the caspase-dependent apoptotic pathway, overcome inhibition of hematopoiesis seen in patients with HIV infection, an effect unrelated to their antiviral activity.
Expression of the collagen receptor glycoprotein VI during megakaryocyte differentiation
Authors: Berlanga Oscar , Bobe Regis , Becker Marion , Murphy George , Leduc Mireille , Bon Cassian , Barry Fiona A. , Gibbins Jonathan M. , Garcia Paloma , Frampton Jonathan , Watson Stephen P. 
Published: October 2019

Abstract
This study examined the expression of the platelet collagen receptor glycoprotein VI (GPVI) in megakaryocyte cell lines and primary megakaryocytes by reverse transcriptase-polymerase chain reaction and by flow cytometry and ligand blotting using the snake venom toxin convulxin. Expression of GPVI is increased in the megakaryoblastic cell lines HEL and CMK on differentiation with the phorbol ester phorbol 12-myristate 13-acetate (PMA), along with the Fc receptor γ-chain (FcR γ-chain). The increase in GPVI expression is associated with marked potentiation of tyrosine phosphorylation and Ca++ elevation in response to convulxin. Syk, linker for activated T cells, and phospholipase Cγ2 (PLCγ2) are among the proteins tyrosine phosphorylated on convulxin stimulation in PMA-differentiated HEL cells. Studies on primary murine megakaryocytes grown in vitro confirmed that GPVI is up-regulated in parallel with functional activation, assessed by measurement of [Ca++]i, during differentiation. The results demonstrate that expression of GPVI is up-regulated along with the FcR γ-chain during differentiation of megakaryocytes.
Impaired function of circulating HIV-specific CD8+ T cells in chronic human immunodeficiency virus infection
Authors: Shankar Premlata , Russo Melissa , Harnisch Brooke , Patterson Mark , Skolnik Paul , Lieberman Judy 
Published: October 2019

AbstractThe functional status of circulating human immunodeficiency (HIV)-specific CD8 T cells in chronically infected subjects was evaluated. By flow cytometry, only 5 of 7 subjects had detectable CD8 T cells that produced IFN-γ after stimulation with HIV-infected primary CD4 T cells. In 2 subjects, the frequency of IFN-γ–producing cells increased 4-fold when IL-2 was added to the culture medium; in another subject, IFN-γ–producing cells could be detected only after IL-2 was added. IFN-γ–producing cells ranged from 0.4% to 3% of CD8 T cells. Major histocompatibility complex–peptide tetramer staining, which identifies antigen-specific T cells irrespective of function, was used to evaluate the proportion of HIV-specific CD8 T cells that may be nonfunctional in vivo. CD8 T cells binding to tetramers complexed to HIV gag epitope SLYNTVATL and reverse transcriptase epitope YTAFTIPSI were identified in 9 of 15 and 5 of 12 HLA-A2–expressing seropositive subjects at frequencies of 0.1% to 1.1% and 0.1 to 0.7%, respectively. Freshly isolated tetramer-positive cells expressed a mixed pattern of memory and effector markers. On average, IFN-γ was produced by less than 25% of tetramer-positive CD8 T cells after stimulation with the relevant gag or reverse transcriptase peptide. In all subjects tested, freshly isolated CD8 T cells were not cytolytic against peptide-pulsed B lymphoblastoid cell line or primary HIV-infected CD4 T-cell targets. Exposure to IL-2 enhanced the cytotoxicity of CD8 T cells against primary HIV-infected CD4 targets in 2 of 2 subjects tested. These results suggest that a significant proportion of HIV-specific CD8 T cells may be functionally compromised in vivo and that some function can be restored by exposure to IL-2.
Mutations of the AML1 gene in myelodysplastic syndrome and their functional implications in leukemogenesis
Authors: Imai Yoichi , Kurokawa Mineo , Izutsu Koji , Hangaishi Akira , Takeuchi Kengo , Maki Kazuhiro , Ogawa Seishi , Chiba Shigeru , Mitani Kinuko , Hirai Hisamaru 
Published: October 2019

AbstractThe AML1 gene encodes a DNA-binding protein that contains the runt domain and is the most frequent target of translocations associated with human leukemias. Here, point mutations of the AML1 gene, V105ter (single-letter amino acid code) and R139G, (single-letter amino acid codes) were identified in 2 cases of myelodysplastic syndrome (MDS) by means of the reverse transcriptase–polymerase chain reaction single-strand conformation polymorphism method. Both mutations are present in the region encoding the runt domain of AML1 and cause loss of the DNA-binding ability of the resultant products. Of these mutants, V105ter has also lost the ability to heterodimerize with polyomavirus enhancer binding protein 2/core binding factor β (PEBP2β/CBFβ). On the other hand, the R139G mutant acts as a dominant negative inhibitor by competing with wild-type AML1 for interaction with PEBP2β/CBFβ. This study is the first report that describes mutations of AML1 in patients with MDS and the mechanism whereby the mutant acts as a dominant negative inhibitor of wild-type AML1.
Adhesion to 90K (Mac-2 BP) as a mechanism for lymphoma drug resistance in vivo
Authors: Fornarini Bruna , D'Ambrosio Consuelo , Natoli Clara , Tinari Nicola , Silingardi Vittorio , Iacobelli Stefano 
Published: October 2019

AbstractA cell-adhesive protein of the human serum, 90K binds galactin-3, β1-integrins, collagens, and fibronectin, and it is of importance in cell-cell and cell–extracellular matrix adhesion. Serum 90K levels in 137 patients with lymphoma were measured by enzyme-linked immunosorbent assay. Compared with healthy controls, pretreatment serum 90K levels in patients with lymphoma were elevated (P &lt; .001). Of 97 patients who showed objective response to treatment, 20 (21%) had pretreatment 90K levels above the normal cutoff compared with 17 (53%) of 32 patients who did not respond (P = .002). When used as a plastic-immobilized substrate, 90K caused a significant reduction in chemotherapy-induced apoptosis of Jurkat T lymphoma cells. This finding could explain the lack of response in lymphoma patients with high 90K serum levels.
Development and validation of an algorithm to assess risk of first-time falling among home care clients
Authors: Kuspinar Ayse , Hirdes John P. , Berg Katherine , McArthur Caitlin , Morris John N. 
Published: October 2019

Abstract

Background
The falls literature focuses on individuals with previous falls, so little is known about individuals who have not experienced a fall in the past. Predicting falls in those without a prior event is critical for primary prevention of injuries. Identifying and intervening before the first fall may be an effective strategy for reducing the high personal and economic costs of falls among older adults. The purpose of this study was to derive and validate a prediction algorithm for first-time falls (1stFall) among home care clients who had not fallen in the past 90 days.

Methods
Decision tree analysis was used to develop a prediction algorithm for the occurrence of a first fall from a cohort of home care clients who had not fallen in the last 90 days, and who were prospectively followed over 6 months. Ontario home care clients who were assessed with the Resident Assessment Instrument-Home Care (RAI-HC) between 2002 and 2014 (n = 88,690) were included in the analysis. The dependent variable was falls in the past 90 days in follow-up assessments. The independent variables were taken from the RAI-HC. The validity of the 1stFall algorithm was tested among home care clients in 4 Canadian provinces: Ontario (n = 38,013), Manitoba (n = 2738), Alberta (n = 1226) and British Columbia (n = 9566).

Results
The 1stFall algorithm includes the utilization of assistive devices, unsteady gait, age, cognition, pain and incontinence to identify 6 categories from low to high risk. In the validation samples, fall rates and odds ratios increased with risk levels in the algorithm in all provinces examined.

Conclusions
The 1stFall algorithm predicts future falls in persons who had not fallen in the past 90 days. Six distinct risk categories demonstrated predictive validity in 4 independent samples.
Effect of attending pregnant women’s conference on institutional delivery, Northwest Ethiopia: comparative cross-sectional study
Authors: Asresie Melash Belachew , Dagnew Gizachew Worku 
Published: October 2019

Abstract

Background
Institutional delivery is the cornerstone reducing maternal mortality. Community-based behavioral change interventions are increasing institutional delivery in developing countries. Yet, there is a dearth of information on the effect of attending pregnant women’s conferences in improving institutional delivery in Ethiopian. Therefore, this study was aimed to assess the effect of attending pregnant women’s conference on institutional delivery, Northwest Ethiopia.

Methods
Community-based comparative cross-sectional study was conducted in 2017 among 871 women who gave birth within the last 12 months (435: pregnant women’s conference attendants and 436: pregnant women’s conference non-attendants). Participants were selected by using a multistage-simple random sampling technique and a structured interviewer-administered questionnaire was used for data collection. Both descriptive and logistic regression analyses were performed using SPSS V.23. A P-value less than or equal to 0.05 at 95% confidence interval was set to test statistical significance.

Results
Institutional delivery among women who attended pregnant women’s conferences was 54.3%, higher compared with 39.9% of women who didn’t attend the conference. Likewise, the level of well-preparedness for birth was higher among women who attended the conference (38.9%) compared with their counterparts (25.7%). Being knowledgeable on childbirth (AOR = 1.7, 95%CI: 1.2, 2.8) and postpartum danger signs (AOR = 14.0, 95%CI: 4.6, 40.0), and discussed with partners/families about the place of birth (AOR = 7.7, 95%CI: 3.6, 16.4) were more likely to institutional delivery among women who attended pregnant women’s conference. Whereas, among women who didn’t attend the pregnant women’s conference, being knowledgeable about pregnancy danger signs (AOR = 3.6, 95%CI: 1.6, 8.1) were more likely to institutional delivery. In addition, the nearest health facility within 1 h of walking and well-preparedness for birth and its complication were found positively associated with institutional delivery in both groups.

Conclusion
Institutional delivery was low in both groups compared to the national plan, but was higher among women who attended the conference. Similarly, women’s knowledge of obstetric danger signs and preparation for birth and its complication was higher among women who attended the conference. Therefore, encouraging women to attend the pregnant women’s conference and discuss with their families about the place of delivery should be strengthened.
Efficacy of mepolizumab for patients with severe asthma and eosinophilic chronic rhinosinusitis
Authors: Numata Takanori , Nakayama Katsutoshi , Utsumi Hirofumi , Kobayashi Kenji , Yanagisawa Haruhiko , Hashimoto Mitsuo , Minagawa Shunsuke , Ishikawa Takeo , Hara Hiromichi , Araya Jun , Kuwano Kazuyoshi 
Published: October 2019

Abstract

Background
Several major randomized control studies have demonstrated that mepolizumab, an anti-IL-5 monoclonal antibody, is effective for patients with severe eosinophilic asthma who show exacerbation or require systemic corticosteroid maintenance therapy. However, the predictive factors of the response to mepolizumab other than blood eosinophil count are unclear in clinical practice.

Objective
To elucidate the predictive factors of the response to mepolizumab for patients with severe eosinophilic asthma.

Methods
From July 2016 to December 2017, 28 patients with severe asthma received mepolizumab in our hospital. To determine the predictive factors, we retrospectively evaluated patient characteristics, comorbidities, biomarkers, pulmonary function, maintenance dose of systemic corticosteroids and number of exacerbations.

Results
The response rate to mepolizumab treatment was 70% (19/27; one pregnant woman was excluded from analysis). Compared with 11 patients without eosinophilic chronic rhinosinusitis (ECRS), 16 patients with ECRS showed significantly improved systemic corticosteroid-sparing effects [− 71.3 ± 37.0% vs − 10.7 ± 20.1%, P = 0.006], change from baseline FeNO [− 19 ± 57 (%) vs 30 ± 77 (%), P = 0.023] and symptoms [14 patients (88%) vs five patients (45%), P = 0.033]. ECRS was identified as a predictive factor of the response to mepolizumab in a multivariate logistic regression analysis [odds ratio = 22.5, 95% CI (1.5–336), P = 0.024]. Of the eight patients previously administered omalizumab, five responded to mepolizumab. Staphylococcus aureus enterotoxin B IgE results were negative in 80% of responders (P = 0.14).

Conclusion
Both groups showed improved symptom scores and a decreased number of exacerbations. Mepolizumab substantially improved the clinical variables of patients with eosinophilic asthma complicated with ECRS.
Metagenomics: aid to combat antimicrobial resistance in diarrhea
Authors: De Rituparna 
Published: October 2019

Abstract
Antimicrobial resistance (AMR) has emerged as an obstacle in the supple administration of antimicrobial agents to critical diarrheal patients. Most diarrheal pathogens have developed resistance against the major classes of antibiotics commonly used for assuaging diarrheal symptoms. Antimicrobial resistance develops when pathogens acquire antimicrobial resistance genes (ARGs) through genetic recombination from commensals and pathogens. These are the constituents of the complex microbiota in all ecological niches. The recombination events may occur in the environment or in the gut. Containment of AMR can be achieved through a complete understanding of the complex and diverse structure and function of the microbiota. Its taxonomic entities serve as focal points for the dissemination of antimicrobial resistance genetic determinants. Molecular methods complemented with culture-based diagnostics have been historically implemented to document these natural events. However, the advent of next-generation sequencing has revolutionized the field of molecular epidemiology. It has revolutionized the method of addressing relevant problems like diagnosis and surveillance of infectious diseases and the issue of antimicrobial resistance. Metagenomics is one such next-generation technique that has proved to be a monumental advancement in the area of molecular taxonomy. Current understanding of structure, function and dysbiosis of microbiota associated with antimicrobial resistance was realized due to its conception. This review describes the major milestones achieved due to the advent and implementation of this new technique in the context of antimicrobial resistance. These achievements span a wide panorama from the discovery of novel microorganisms to invention of translational value.
A cellular and proteomic approach to assess proteins extracted from cryopreserved human amnion in the cultivation of corneal stromal keratocytes for stromal cell therapy
Authors: Fenner Beau J. , Yusoff Nur Zahirah B. M. , Fuest Matthias , Zhou Lei , Bandeira Francisco , Cajucom-Uy Howard Y. , Tan H. K. , Mehta Jodhbir S. , Yam Gary H. F. 
Published: October 2019

AbstractBackgroundHuman corneal stromal keratocytes propagated in culture media supplemented with human amnion extract (AME) can correct early corneal haze in an animal model. Clinical application of cultivated keratocytes is limited by infectious disease screening before amnion products can be used in humans. It remains unclear if AME from cryopreserved versus fresh human amnion can support human keratocyte propagation, and which components of the extract promote keratocyte growth.MethodsThree placentas were collected for the preparation of fresh and cryopreserved amnion tissues followed by homogenization and protein extraction. AME protein profiles were studied using isobaric tagging for relative and absolute quantitation (iTRAQ) proteomics. Enriched gene ontology (GO) terms and functional classes were identified. Primary human keratocytes from 4 donor corneas were cultured in media supplemented with fresh AME (F-AME) or cryopreserved AME (C-AME). Cell viability, proliferation and keratocyte marker expression were examined by confocal immunofluorescence and flow cytometry.ResultsAME proteomics revealed 1385 proteins with similar expression levels (between 0.5- and 2-fold) between F- and C-AME, while 286 proteins were reduced (less than 0.5-fold) in C-AME. Enriched GO term and biological pathway analysis showed that those proteins with comparable expression between F-AME and C-AME were involved in cell metabolism, epithelial-mesenchymal transition, focal adhesion, cell-extracellular matrix interaction, cell stress regulation and complement cascades. Human corneal stromal keratocytes cultured with F-AME or C-AME showed similar morphology and viability, while cell proliferation was mildly suppressed with C-AME (P > 0.05). Expression of aldehyde dehydrogenase 3A1 (ALDH3A1) and CD34 was similar in both cultures.ConclusionAME from cryopreserved amnion had limited influence on keratocyte culture. It is feasible to use protein extract from cryopreserved amnion to propagate human keratocytes for potential translational applications.
Germline GPR161 Mutations Predispose to Pediatric Medulloblastoma
Authors: Begemann Matthias , Waszak Sebastian M. , Robinson Giles W. , Jäger Natalie , Sharma Tanvi , Knopp Cordula , Kraft Florian , Moser Olga , Mynarek Martin , Guerrini-Rousseau Lea , Brugieres Laurence , Varlet Pascale , Pietsch Torsten , Bowers Daniel C. , Chintagumpala Murali , Sahm Felix , Korbel Jan O. , Rutkowski Stefan , Eggermann Thomas , Gajjar Amar , Northcott Paul , Elbracht Miriam , Pfister Stefan M. , Kontny Udo , Kurth Ingo 
Published: October 2019

PURPOSE The identification of a heritable tumor predisposition often leads to changes in management and increased surveillance of individuals who are at risk; however, for many rare entities, our knowledge of heritable predisposition is incomplete. METHODS Families with childhood medulloblastoma, one of the most prevalent childhood malignant brain tumors, were investigated to identify predisposing germline mutations. Initial findings were extended to genomes and epigenomes of 1,044 medulloblastoma cases from international multicenter cohorts, including retrospective and prospective clinical studies and patient series. RESULTS We identified heterozygous germline mutations in the G protein-coupled receptor 161 ( GPR161) gene in six patients with infant-onset medulloblastoma (median age, 1.5 years). GPR161 mutations were exclusively associated with the sonic hedgehog medulloblastoma (MBSHH) subgroup and accounted for 5% of infant MBSHH cases in our cohorts. Molecular tumor profiling revealed a loss of heterozygosity at GPR161 in all affected MBSHH tumors, atypical somatic copy number landscapes, and no additional somatic driver events. Analysis of 226 MBSHH tumors revealed somatic copy-neutral loss of heterozygosity of chromosome 1q as the hallmark characteristic of GPR161 deficiency and the primary mechanism for biallelic inactivation of GPR161 in affected MBSHH tumors. CONCLUSION Here, we describe a novel brain tumor predisposition syndrome that is caused by germline GPR161 mutations and characterized by MBSHH in infants. Additional studies are needed to identify a potential broader tumor spectrum associated with germline GPR161 mutations.
A case of transsexualism among close relatives
Authors: Kozlov G. I. , Kalinchenko S. Yu. 
Published: October 2019

Transsexualism (TS) is a mismatch between sexual auto-identification and biological and genetic sex.
This is a rather rare pathology. According to most authors. male TS significantly prevails over female (3:1 ratio).
Over the period from 1980 to the present, we have observed 149 patients with TS, including 124 with female TS (transgender women and men) and 20 with male TS (transgender men and women). According to our observations, female TS prevails over male in a 3:1 ratio, which is at variance with data from researchers in other countries. The question of the reasons for this discrepancy remains to be answered.
The essence of the TS is still completely unclear. However, attempts to interpret the pathogenesis of TS from a purely psychiatric perspective, that is, within the framework of a depersonalization syndrome, are now completely abandoned. Recently, much attention has been paid to genetic and endocrine factors that can create the prerequisites for the development of TS.