bluuebunny/crossref_metadata_2025_split huggingface dataset:
Branch Retinal Artery Occlusion Following Intravitreal Injection of Methotrexate for the Treatment of Primary Vitreoretinal Lymphoma
Authors: Venkat Arthi G. , Karthik Naveen , Lowe Ashley , Sharma Sumit 
Published: September 2019

Purpose: This paper reports a case of an older white woman presenting with recalcitrant bilateral vitreoretinal inflammation that was ultimately proven to be primary vitreoretinal lymphoma by vitreous biopsy who subsequently developed a branch retinal artery occlusion (BRAO) following an intravitreal injection of methotrexate. Methods: Case summary. Results: The patient was treated with serial intravitreal methotrexate injections and subsequently developed a BRAO immediately following her seventh injection. Conclusions: A full systemic evaluation to rule out other causes of the BRAO was negative and given the timing of her symptoms after the injection it was determined that the BRAO was most likely realted to the intravitreal methotrexate injection.
Distinct immune composition in lymph node and peripheral blood of CLL patients is reshaped during venetoclax treatment
Authors: de Weerdt Iris , Hofland Tom , de Boer Renate , Dobber Johan A. , Dubois Julie , van Nieuwenhuize Denise , Mobasher Mehrdad , de Boer Fransien , Hoogendoorn Mels , Velders Gerjo A. , van der Klift Marjolein , Remmerswaal Ester B. M. , Bemelman Frederike J. , Niemann Carsten U. , Kersting Sabina , Levin Mark-David , Eldering Eric , Tonino Sanne H. , Kater Arnon P. 
Published: September 2019

AbstractMorbidity and mortality due to immunosuppression remain among the foremost clinical challenges in chronic lymphocytic leukemia (CLL). Although immunosuppression is considered to originate within the lymph node (LN) microenvironment, alterations in T and natural killer (NK) cells have almost exclusively been studied in peripheral blood (PB). Whereas chemoimmunotherapy further deteriorates immune function, novel targeted agents like the B-cell lymphoma 2 inhibitor venetoclax potentially spare nonmalignant lymphocytes; however, the effects of venetoclax on nonleukemic cells have not been explored. We address these unresolved issues using a comprehensive analysis of nonmalignant lymphocytes in paired LN and PB samples from untreated CLL patients, and by analyzing the effects of venetoclax-based treatment regimens on the immune system in PB samples from previously untreated and relapsed/refractory patients. CLL-derived LNs contained twice the amount of suppressive regulatory T cells (Tregs) and CLL supportive follicular T helper (Tfh) cells compared with PB. This was accompanied by a low frequency of cytotoxic lymphocytes. The expression of PD-1 by CD8+ T cells was significantly higher in LN compared with PB. Venetoclax-based treatment led to deep responses in the majority of patients, but also to decreased absolute numbers of B, T, and NK cells. Tfh cell, Treg, and PD-1+ CD8+ T cell numbers were reduced more than fivefold after venetoclax-based therapy, and overproduction of inflammatory cytokines was reduced. Furthermore, we observed restoration of NK cell function. These data support the notion that the immunosuppressive state in CLL is more prominent within the LN. Venetoclax-based regimens reduced the immunosuppressive footprint of CLL, suggesting immune recovery after the elimination of leukemic cells.
Decoding the role of SOD2 in sickle cell disease
Authors: Dosunmu-Ogunbi Atinuke M. , Wood Katherine C. , Novelli Enrico M. , Straub Adam C. 
Published: September 2019

AbstractSickle cell disease (SCD) is an inherited hemoglobinopathy caused by a single point mutation in the β-globin gene. As a consequence, deoxygenated hemoglobin polymerizes triggering red blood cell sickling and hemolysis, vaso-occlusion, and ischemia/reperfusion. Allied to these pathologies is the overproduction of reactive oxygen species driven by hemoglobin Fenton chemistry and peroxidase reactions as well as by secondary activation of vascular oxidases, including NAD(P)H oxidase and xanthine oxidase. In addition, hypoxia, produced by sickle red blood cell occlusion, disrupts mitochondrial metabolism and generates excess superoxide through electron leak from the mitochondrial respiratory chain. Superoxide dismutase 2 (SOD2) is a mitochondrial-specific antioxidant enzyme that dismutates superoxide to hydrogen peroxide, which is then converted to water by catalase and glutathione peroxidase. In SCD, the antioxidant defense system is significantly diminished through decreased expression and activity levels of antioxidant enzymes, including superoxide dismutase, catalase, and glutathione peroxidase. From a translational perspective, genetic variants including a missense variant in SOD2 (valine to alanine at position 16) are present in 45% of people with African ancestry and are associated with increased sickle complications. While it is known that there is an imbalance between oxidative species and antioxidant defenses in SCD, much more investigation is warranted. This review summarizes our current understanding of antioxidant defense systems in SCD, particularly focused on SOD2, and provides insight into challenges and opportunities as the field moves forward.
Reticulocyte and red blood cell deformation triggers specific phosphorylation events
Authors: Moura Pedro L. , Lizarralde Iragorri Maria A. , Français Olivier , Le Pioufle Bruno , Dobbe Johannes G. G. , Streekstra Geert J. , El Nemer Wassim , Toye Ashley M. , Satchwell Timothy J. 
Published: September 2019

AbstractThe capacity to undergo substantial deformation is a defining characteristic of the red blood cell (RBC), facilitating transit through the splenic interendothelial slits and microvasculature. Establishment of this remarkable property occurs during a process of reticulocyte maturation that begins with egress through micron-wide pores in the bone marrow and is completed within the circulation. The requirement to undertake repeated cycles of deformation necessitates that both reticulocytes and erythrocytes regulate membrane-cytoskeletal protein interactions in order to maintain cellular stability. In the absence of transcriptional activity, modulation of these interactions in RBCs is likely to be achieved primarily through specific protein posttranslational modifications, which at present remain undefined. In this study, we use high-throughput methods to define the processes that underlie the response to deformation and shear stress in both reticulocytes and erythrocytes. Through combination of a bead-based microsphiltration assay with phosphoproteomics we describe posttranslational modification of RBC proteins associated with deformation. Using microsphiltration and microfluidic biochip-based assays, we explore the effect of inhibiting kinases identified using this dataset. We demonstrate roles for GSK3 and Lyn in capillary transit and maintenance of membrane stability following deformation and show that combined inhibition of these kinases significantly decreases reticulocyte capacity to undergo repeated deformation. Finally, we derive a comprehensive and integrative phosphoproteomic dataset that provides a valuable resource for further mechanistic dissection of the molecular pathways that underlie the RBC’s response to mechanical stimuli and for the study of reticulocyte maturation.
Using wearables and self-management apps in patients with COPD: a qualitative study
Authors: Wu Robert C. , Ginsburg Shiphra , Son Tatiana , Gershon Andrea S. 
Published: September 2019

BackgroundTechnology such as wearable technology and self-management applications could improve the care of patients with chronic obstructive pulmonary disease (COPD) by real-time continuous monitoring, early detection of COPD and improved self-management. However, patients have not been willing to use technology when it is too difficult to use, interferes with their daily lives or threatens their identity, independence and self-care.MethodsWe conducted a qualitative study to determine what patients with COPD would like to see in a wearable device and a mobile application to help manage their condition. Semi-structured interviews were conducted, recorded and transcribed. Thematic analysis was used to identify themes and concepts.ResultsWe interviewed 14 people with COPD with an average age of 69 years. Participants perceived that the technology could improve their ability to manage their condition both in daily life and during exacerbations by connecting how they feel and by knowing their oxygen saturation, heart rate and activity. The technology may help them address feelings of fear and panic associated with exacerbations and may provide reassurance and connectedness. Some people with COPD wanted their healthcare providers to have access to their data, while others were concerned about inundating them with too much information. Of note, people wanted to maintain control of the information; to make connections with the data, but also in order to be alerted when a possible exacerbation occurs.ConclusionPatients perceived significant potential for wearables and apps to help manage their condition.
Comparison of intrapleural use of urokinase and tissue plasminogen activator/DNAse in pleural infection
Authors: Bédat Benoît , Plojoux Jérôme , Noel Jade , Morel Anna , Worley Jonathan , Triponez Frédéric , Karenovics Wolfram 
Published: September 2019

Fibrinolysis can be used to improve fluid drainage in pleural infection. Treatment with either urokinase or tissue plasminogen activator (t-PA) in association with DNAseviaa chest tube has been effective at reducing the need for surgery. This study is the first to compare the efficacy of these two treatments.We performed a single-centre, controlled, prospective cohort study. All individuals with pleural infection admitted to our hospital between January 2014 and December 2017 who were treated with antibiotics, a chest tube and fibrinolysis were included in this study. The rate of additional procedure requirements (additional chest tube or surgery) after initial fibrinolysis, complications, costs, and radiological and biological outcomes were analysed.Among the 93 patients included in this study, 34% required additional procedures after an initial fibrinolysis, including 21% who received an additional chest tube and 13% who underwent thoracoscopy. The need for additional procedures arose due to presence of multiple pleural collections (p=0.01) and was associated with the use of large-bore drain (p=0.01). The success rate of fibrinolysis was not significantly different between urokinase and t-PA/DNAse (p=0.35). The differences in drainage duration and in length of hospital stay were not significant either (p=0.05 and p=0.12, respectively). Treatment with t-PA/DNAse was cheaper (p=0.04) but was associated with a higher rate of haemothorax (p=0.002).In conclusion, treatment with urokinase is safer and equally effective when compared with treatment with t-PA/DNAse.
Development and validation of the comprehensive assessment scale for chemotherapy–induced peripheral neuropathy in survivors of cancer
Authors: Kanda K. , Fujimoto K. , Mochizuki R. , Ishida K. , Lee B. 
Published: September 2019

Abstract

Background
Appropriate assessment is essential for the management of chemotherapy-induced peripheral neuropathy (CIPN), an intractable symptom that cannot yet be palliated, which is high on the list of causes of distress for cancer patients. However, objective assessment by medical staff makes it easy to underestimate the symptoms and effects of CIPN in cancer survivors. As a result, divergence from subjective evaluation of cancer survivors is a significant problem. Therefore, there is an urgent need to develop a subjective scale with high accuracy and applicability that reflects the experiences of cancer patients. We developed a comprehensive assessment scale for CIPN in cancer survivors, named the Comprehensive Assessment Scale for Chemotherapy-Induced Peripheral Neuropathy in Survivors of Cancer (CAS-CIPN), and demonstrated its reliability and validity.

Methods
We developed a questionnaire based on qualitative studies of peripheral neuropathy in Japanese cancer patients and literature review. Twelve cancer experts confirmed the content validity of the questionnaire. A draft version comprising 40 items was finalized by a pilot test on 100 subjects. The participants in the present study were 327 Japanese cancer survivors. Construct validity was determined by factor analysis, and internal validity by confirmation factor analysis and Cronbach’s α.

Results
Factor analysis showed that the structure consisted of 15 items in four dimensions: “Threatened interference in daily life by negative feelings”, “Impaired hand fine motor skills”, “Confidence in choice of treatment/management,” and “Dysesthesia of the palms and soles.” The CAS-CIPN internal consistency reliability was 0.826, and the reliability coefficient calculated using the Spearman-Brown formula [q = 2r/(1 + r)] was 0.713, confirming high internal consistency and stability. Scores on this scale were strongly correlated with Gynecologic Oncology Group-Neurotoxicity scores (r = 0.714, p < 0.01), confirming its criterion-related validity.

Conclusions
The CAS-CIPN is an assessment tool with high reliability and validity for the comprehensive evaluation of CIPN in cancer survivors. The CAS-CIPN is simple to use, and can be used by medical professionals for appropriate situational assessment and intervention.
Hospitalization at the end of life among nursing home residents with dementia: a systematic review
Authors: Hoffmann Falk , Strautmann Anke , Allers Katharina 
Published: September 2019

Abstract

Background
Half of nursing home residents (NHR) suffer from dementia. End-of-life hospitalizations are often burdensome in residents with dementia. A systematic review was conducted to study the occurrence of hospitalizations at the end of life in NHR with dementia and to compare these figures to NHR without dementia.

Methods
A systematic literature search in MEDLINE, CINAHL and Scopus was conducted in May 2018. Studies were included if they reported proportions of in-hospital deaths or hospitalizations of NHR with dementia in the last month of life. Two authors independently selected studies, extracted data, and assessed quality of studies.

Results
Nine hundred forty-five citations were retrieved; 13 studies were included. Overall, 7 studies reported data on in-hospital death with proportions ranging between 0% in Canada and 53.3% in the UK. Studies reporting on the last 30 days of life (n = 8) varied between 8.0% in the Netherlands and 51.3% in Germany. Two studies each assessed the influence of age and sex. There seem to be fewer end-of-life hospitalizations in older age groups. The influence of sex is inconclusive. All but one study found that at the end of life residents with dementia were hospitalized less often than those without (n = 6).

Conclusions
We found large variations in end-of-life hospitalizations of NHR with dementia, probably being explained by differences between countries. The influence of sex and age might differ when compared to residents without dementia. More studies should compare NHR with dementia to those without and assess the influence of sex and age.

Trial registration
PROSPERO registration number CRD42018104263.
Characterizing an engineered carotenoid-producing yeast as an anti-stress chassis for building cell factories
Authors: Liu Hsien-Lin , Chang Jui-Jen , Thia Caroline , Lin Yu-Ju , Lo Shou-Chen , Huang Chieh-Chen , Li Wen-Hsiung 
Published: September 2019

Abstract

Background
A microorganism engineered for non-native tasks may suffer stresses it never met before. Therefore, we examined whether a Kluyveromyces marxianus strain engineered with a carotenoid biosynthesis pathway can serve as an anti-stress chassis for building cell factories.

Results
Carotenoids, a family of antioxidants, are valuable natural products with high commercial potential. We showed that the free radical removal ability of carotenoids can confer the engineered host with a higher tolerance to ethanol, so that it can produce more bio-ethanol than the wild type. Moreover, we found that this engineered strain has improved tolerance to other toxic effects including furfurals, heavy metals such as arsenate (biomass contaminant) and isobutanol (end product). Furthermore, the enhanced ethanol tolerance of the host can be applied to bioconversion of a natural medicine that needs to use ethanol as the delivery solvent of hydrophobic precursors. The result suggested that the engineered yeast showed enhanced tolerance to ethanol-dissolved hydrophobic 10-deacetylbaccatin III, which is considered a sustainable precursor for paclitaxel (taxol) bioconversion.

Conclusions
The stress tolerances of the engineered yeast strain showed tolerance to several toxins, so it may serve as a chassis for cell factories to produce target products, and the co-production of carotenoids may make the biorefinary more cost-effective.
A systematic approach to study the pH-dependent release, productivity and product specificity of dextransucrases
Authors: Schmid Jonas , Bechtner Julia , Vogel Rudi F. , Jakob Frank 
Published: September 2019

AbstractBackgroundDextransucrases are extracellular enzymes, which catalyze the formation of α-1→6-linked glucose polymers from sucrose. These enzymes are exclusively expressed by lactic acid bacteria, which commonly acidify the extracellular environment due to their physiology. Dextransucrases are thus confronted with steadily changing reaction conditions in regards to the environmental pH, which can further affect the amount of released dextransucrases. In this work, we studied the effect of the environmental pH on the release, the productivity and the product specificity of the dextransucrase expressed byLactobacillus(L.)hordeiTMW 1.1822. Dextransucrases were recovered as crude extracts at pH 3.5–pH 6.5 and then again used to produce dextrans at these pH values. The respectively produced dextran amounts and sizes were determined and the obtained results finally systematically correlated.ResultsMaximum dextran amounts were produced at pH 4.0 and pH 4.5, while the productivity of the dextransucrases significantly decreased at pH 3.5 and pH 6.5. The distribution of dextran amounts produced at different pH most likely reflects the pH dependent activity of the dextransucrases released byL. hordei, since different transglycosylation rates were determined at different pH using the same dextransucrase amounts. Moreover, similar hydrolysis activities were detected at all tested conditions despite significant losses of transglycosylation activities indicating initial hydrolysis prior to transglycosylation reactions. The molar masses and rms radii of dextrans increased up to pH 5.5 independently of the stability of the enzyme. The gelling properties of dextrans produced at pH 4.0 and pH 5.5 were different.ConclusionsThe presented methodological approach allows the controlled production of dextrans with varying properties and could be transferred and adapted to other microbes for systematic studies on the release and functionality of native sucrases or other extracellular enzymes.
Head and neck cancer survivors’ preferences for and evaluations of a post-treatment dietary intervention
Authors: Crowder Sylvia L. , Douglas Katherine G. , Frugé Andrew D. , Carroll William R. , Spencer Sharon A. , Locher Julie L. , Demark-Wahnefried Wendy , Rogers Laura Q. , Arthur Anna E. 
Published: September 2019

Abstract

Background
Dietary preferences vary depending on cancer type. The purpose of this study was to report dietary intervention preferences and a study program evaluation from post-treatment head and neck cancer survivors participating in a dietary intervention.

Methods
Between January 2015 and August 2016, 24 head and neck cancer survivors participated in a 12-week randomized clinical dietary intervention trial that promoted weekly consumption of 2.5 cups of cruciferous vegetables and 3.5 cups of green leafy vegetables. At study completion, survivors completed a preferences survey and a study program evaluation to probe interests and improvement aspects for planning future dietary intervention trials. Descriptive statistics (means and frequencies) were generated for multiple choice question responses. Responses to open-ended questions were recorded and grouped based on themes, and verified by quality assurance checks by a second study team member.

Results
Twenty-three survivors completed the preferences and evaluation surveys (response rate 96%). Overall, most participants reported a preference for one-on-one telephone counseling from a registered dietitian nutritionist before beginning treatment. Ninety-six percent of participants ranked the overall study program as “very good” to “excellent,” and all agreed the objectives of the study were clear, the study staff was helpful and easy to contact, and the registered dietitian nutritionist was knowledgeable.

Conclusions
Future research and dietary intervention planning for head and neck cancer survivors should focus on strategies to promote one-on-one telephone or other distance-based counseling combined with face-to-face visits, according to survivor preference.
Fibroblast-derived CXCL12 regulates PTEN expression and is associated with the proliferation and invasion of colon cancer cells via PI3k/Akt signaling
Authors: Ma Jiachi , Sun Xiaowen , Wang Yimin , Chen Bangling , Qian Liyu , Wang Yaguo 
Published: September 2019

Abstract

Background
Stromal-derived CXCL12 play an important role which influence the proliferation and invasiveness of colon cancer in microenvironment. The present study aimed to analyze the underlying mechanism by which CXCL12 and tumour suppressor protein phosphatase and tensin homologue deleted on chromosome 10 (PTEN) influences the metastatic potential of colon cancer and internal relation of colon cancer and stromal cells.

Methods
RT-PCR and western blot were detected the expression of CXCL12, CXCR4 and PTEN in colon cancer cells and stromal cells. The co-operative effects of CXCL12 and PTEN on proliferation and invasion of colon cancer cells were evaluated by real-time PCR, proliferation and invasion assays using an in vitro system consisting of co-cultured cancer cells and stromal cells. We eventually investigated activation of PI3K/Akt signaling by CXCL12 regulate PTEN and involved in the metastatic process of colon cancer. In addition, we also examine how the knockdown of PTEN influences proliferation and invasion and correlate with CXCL12/CXCR4/PI3K/Akt, determination of PTEN up-down-stream targets that preferentially contribute to tumorigenesis.

Results
Blockage of PTEN phosphorylation led to a stronger enhancement of cell proliferation and invasion upon stimulation with CXCL12 via its activation of the PI3K/Akt signaling pathway. Furthermore, knockdown of PTEN by siRNA transfection was also found to enhance the activation of the PI3K/Akt pathway, thereby promoting cell invasion and proliferation. CXCL12 induced transcriptional down-regulation of activated PTEN and this signaling pathway promotes cell survival. CXCL12/CXCR4/PI3K/Akt cascade may be critical for colon cancer cells to metastasize.

Conclusions
Based on our results, we suggest that the modification of CXCR4, PTEN, or PI3K function might be promising new therapeutic approaches to inhibit the aggressive spread of colon cancer.