bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nrf2 activation in myeloid cells and endothelial cells differentially mitigates sickle cell disease pathology in mice
Authors: Keleku-Lukwete Nadine , Suzuki Mikiko , Panda Harit , Otsuki Akihito , Katsuoka Fumiki , Saito Ritsumi , Saigusa Daisuke , Uruno Akira , Yamamoto Masayuki 
Published: April 2019

AbstractSickle cell disease (SCD) is caused by a monogenic mutation of the β-globin gene and affects millions of people worldwide. SCD is associated with sustained hemolytic anemia, vasoocclusion, ischemia-reperfusion injury, oxidative tissue damage, inflammatory cell activation, and systemic endothelial dysfunction. The transcription factor Nrf2 coordinates the expression of a wide variety of genes encoding antioxidant, detoxification, and metabolic enzymes. Nrf2 participates in suppressing proinflammatory cytokines and organ protection in SCD. However, little is known regarding the mechanisms by which Nrf2 ameliorates SCD pathology or how some cells respond to Nrf2 stimuli to alleviate SCD pathology. Here, we asked whether monocytes/granulocytes and/or endothelial cells are particularly critical in alleviating the pathology of SCD. By targeting these cells with a Cre recombinase system, we generated SCD::Keap1F/F::LysM-Cre and Tie1-Cre mice with constitutive Nrf2 activation in monocytes/granulocytes and endothelial cells, respectively. Analyses of SCD::Keap1F/F::LysM-Cre and SCD::Keap1F/F::Tie1-Cre mice revealed significantly reduced inflammation, along with decreased white blood cell counts and lower Tnfα and Il1β expression in the lungs. Notably, SCD::Keap1F/F::LysM-Cre mice exhibited reduced heme distribution in the liver, consistent with a decrease in the damaged areas. Vascular function in SCD::Keap1F/F::Tie1-Cre mice was significantly improved, with a 50% decrease in vascular leakage and low expression of the adhesion molecules Vcam1 and P-selectin. Thus, Nrf2 activation in monocytes/granulocytes and endothelial cells contributes differentially and cooperatively to the improvement of SCD pathology.
Rational cotargeting of HDAC6 and BET proteins yields synergistic antimyeloma activity
Authors: Carew Jennifer S. , Espitia Claudia M. , Zhao Weiguo , Visconte Valeria , Anwer Faiz , Kelly Kevin R. , Nawrocki Steffan T. 
Published: April 2019

AbstractInhibition of bromodomain and extra terminal (BET) protein family members, including BRD4, decreases the expression of c-MYC and other key oncogenic factors and also significantly induces histone deacetylase 6 (HDAC6) expression. On the basis of the role of HDAC6 in malignant pathogenesis, we hypothesized that rational cotargeting of HDAC6 and BET family proteins may represent a novel approach that yields synergistic antimyeloma activity. We used genetic and pharmacologic approaches to selectively impair HDAC6 and BET function and evaluated the consequential impact on myeloma pathogenesis. These studies identified HDAC6 upregulation as an efficacy reducing mechanism for BET inhibitors because antagonizing HDAC6 activity synergistically enhanced the activity of JQ1 in a panel of multiple myeloma (MM) cell lines and primary CD138+ cells obtained from patients with MM. The synergy of this therapeutic combination was linked to significant reductions in c-MYC expression and increases in apoptosis induction. Administration of the clinical HDAC6 inhibitor ricolinostat was very well tolerated and significantly augmented the in vivo antimyeloma activity of JQ1. Ex vivo pharmacodynamic analyses demonstrated that the combination of JQ1 and ricolinostat led to significantly lower MM cell proliferation and increased apoptosis and diminished expression of c-MYC and BCL-2. These data demonstrate that cotargeting of HDAC6 and BET family members is a novel and clinically actionable approach to augment the efficacy of both classes of agents that warrants further investigation.
Metabolomic and molecular insights into sickle cell disease and innovative therapies
Authors: Adebiyi Morayo G. , Manalo Jeanne M. , Xia Yang 
Published: April 2019

AbstractSickle cell disease (SCD) is an autosomal-recessive hemolytic disorder with high morbidity and mortality. The pathophysiology of SCD is characterized by the polymerization of deoxygenated intracellular sickle hemoglobin, which causes the sickling of erythrocytes. The recent development of metabolomics, the newest member of the “omics” family, has provided a powerful new research strategy to accurately measure functional phenotypes that are the net result of genomic, transcriptomic, and proteomic changes. Metabolomics changes respond faster to external stimuli than any other “ome” and are especially appropriate for surveilling the metabolic profile of erythrocytes. In this review, we summarize recent pioneering research that exploited cutting-edge metabolomics and state-of-the-art isotopically labeled nutrient flux analysis to monitor and trace intracellular metabolism in SCD mice and humans. Genetic, structural, biochemical, and molecular studies in mice and humans demonstrate unrecognized intracellular signaling pathways, including purinergic and sphingolipid signaling networks that promote hypoxic metabolic reprogramming by channeling glucose metabolism to glycolysis via the pentose phosphate pathway. In turn, this hypoxic metabolic reprogramming induces 2,3-bisphosphoglycerate production, deoxygenation of sickle hemoglobin, polymerization, and sickling. Additionally, we review the detrimental role of an impaired Lands’ cycle, which contributes to sickling, inflammation, and disease progression. Thus, metabolomic profiling allows us to identify the pathological role of adenosine signaling and S1P-mediated erythrocyte hypoxic metabolic reprogramming and hypoxia-induced impaired Lands' cycle in SCD. These findings further reveal that the inhibition of adenosine and S1P signaling cascade and the restoration of an imbalanced Lands' cycle have potent preclinical efficacy in counteracting sickling, inflammation, and disease progression.
Characterization of a cryptic IGH/CCND1 rearrangement in a case of mantle cell lymphoma with negative CCND1 FISH studies
Authors: Peterson Jess F. , Baughn Linda B. , Ketterling Rhett P. , Pitel Beth A. , Smoley Stephanie A. , Vasmatzis George , Smadbeck James B. , Greipp Patricia T. , Mangaonkar Abhishek A. , Thompson Carrie A. , Parikh Sameer A. , Chen Dong , Viswanatha David S. 
Published: April 2019

Key Points
This article characterizes a cryptic IGH/CCND1 rearrangement in MCL by NGS. Mate-pair sequencing can help in accurately diagnosing MCL in cases of cyclin-D1–positive B-cell lymphoma with negative CCND1 FISH studies.
Foot orthoses alter lower limb biomechanics but not jump performance in basketball players with and without flat feet
Authors: Ho Malia , Kong Pui Wah , Chong Lowell Jia‐Yee , Lam Wing‐Kai 
Published: April 2019

AbstractBackgroundFlat‐footed individuals are believed to have poorer jump performance compared to normal‐arched individuals. Foot orthoses are commonly used to support the deformed foot arch, and improve normal foot function. However, it is unclear if foot orthoses use affects jump performance in athletes. Our study aims to investigate if foot type and/or foot orthosis influence countermovement jump (CMJ) and standing broad jump (SBJ) performance and lower limb biomechanics.MethodsTwenty‐six male basketball players were classified into normal‐arched (n = 15) or flat‐footed (n = 11) groups using the Chippaux‐Smirak index, navicular drop test, and the resting calcaneal angle measurement. They performed jumps with and without prefabricated foot orthoses. We measured jump height and distance for CMJ and SBJ, respectively. Hip, knee and ankle joint angles, angular velocities, moments and powers during take‐off were also measured.ResultsFor CMJ, the flat‐footed group exhibited less ankle plantarflexion (F1,24 = 8.407, p = 0.008, ηp2 = 0.259 large effect) and less hip joint power (F1,24 = 7.416, p = 0.012, ηp2 = 0.244 large effect) than the normal‐arched group. Foot orthoses reduced ankle eversion in both groups (F1,24 = 6.702, p = 0.016, ηp2 = 0.218 large effect). For SBJ, the flat‐footed group produced lower peak hip angular velocity (F1,24 = 7.115, p = 0.013, ηp2 = 0.229 large effect) and generated lower horizontal GRF (F1,24 = 5.594, p = 0.026, ηp2 = 0.189 large effect) than the normal‐arched group. Wearing foot orthoses reduced ankle eversion (F1,24 = 5.453, p = 0.028, ηp2 = 0.185 large effect), peak horizontal GRF (F1,24 = 13.672, p = 0.001, ηp2 = 0.363 large effect) and frontal plane ankle moment (F1,24 = 4.932, p = 0.036, ηp2 = 0.170 large effect).ConclusionFoot type and the use of foot orthoses influence take‐off biomechanics, but not actual CMJ and SBJ performances in basketball players. Compared to the normal‐arched individuals, flat‐footed athletes generated smaller propulsion GRF and lower hip flexion velocity and power, which suggests possible compensatory movement strategies to maximise jump performance. Future studies may investigate whether these altered biomechanics, taking into consideration their respective magnitude and effect sizes, may have implications on lower limb injuries. The use of foot orthoses resulted in biomechanical changes in both the normal‐arched and flat‐footed groups but does not enhance jumping performance.
Full-volume 3D seismic interpretation methods: A new step towards high-resolution seismic stratigraphy
Authors: Paumard Victorien , Bourget Julien , Durot Benjamin , Lacaze Sébastien , Payenberg Tobi , George Annette D. , Lang Simon 
Published: April 2019

Following decades of technological innovation, geologists now have access to extensive 3D seismic surveys across sedimentary basins. Using these voluminous data sets to better understand subsurface complexity relies on developing seismic stratigraphic workflows that allow very high-resolution interpretation within a cost-effective timeframe. We have developed an innovative 3D seismic interpretation workflow that combines full-volume and semi-automated horizon tracking with high-resolution 3D seismic stratigraphic analysis. The workflow consists of converting data from seismic (two-way traveltime) to a relative geological time (RGT) volume, in which a relative geological age is assigned to each point of the volume. The generation of a horizon stack is used to extract an unlimited number of chronostratigraphic surfaces (i.e., seismic horizons). Integrated stratigraphic tools may be used to navigate throughout the 3D seismic data to pick seismic unconformities using standard seismic stratigraphic principles in combination with geometric attributes. Here, we applied this workflow to a high-quality 3D seismic data set located in the Northern Carnarvon Basin (North West Shelf, Australia) and provided an example of high-resolution seismic stratigraphic interpretation from an Early Cretaceous shelf-margin system (Lower Barrow Group). This approach is used to identify 73 seismic sequences (i.e., clinothems) bounded by 74 seismic unconformities. Each clinothem presents an average duration of approximately 63,000 years (fifth stratigraphic order), which represents an unprecedented scale of observation for a Cretaceous depositional system on seismic data. This level of interpretation has a variety of applications, including high-resolution paleogeographical reconstructions and quantitative analysis of subsurface data. This innovative workflow constitutes a new step in seismic stratigraphy because it enables interpreters to map seismic sequences in a true 3D environment by taking into account the full variability of depositional systems at high frequency through time and space.
Randomized Phase II Trial to Compare the Efficacy of Haloperidol and Olanzapine in the Control of Chemotherapy-Induced Nausea and Vomiting in Nepal
Authors: Dulal Soniya , Paudel Bishnu Dutta , Neupane Prakash , Shah Aarati , Acharya Bibek , Poudyal Bishesh Sharma , Shilpakar Ramila , Wood Lori Anne 
Published: April 2019

PURPOSE The purpose of the study was to compare efficacy and toxicity of olanzapine (OLN; a higher-cost drug) and haloperidol (HAL; a lower-cost drug) in the prevention of chemotherapy-induced nausea and vomiting (CINV) in patients who receive highly emetogenic chemotherapy (HEC). PATIENTS AND METHODS In a randomized, phase II trial, patients were randomly assigned to receive either OLN 10 mg orally on days 1 to 4 or HAL 1 mg orally on day 1 and 0.5 mg twice daily on days 2 to 4. Both groups received ondansetron 16 mg and dexamethasone 12 mg intravenously on day 1. Patients recorded their nausea using the Edmonton Symptom Assessment Scale (ESAS) and recorded daily episodes of vomiting from day 1 to day 5. The primary end point was complete nausea prevention (CNP; ie, ESAS of 0). Secondary end point was complete emesis prevention (CEP). RESULTS Sixty-five patients were randomly assigned, and 64 received their allocated treatment (n = 32 in each arm). There was no difference in CNP during the overall period (days 1 to 5) between OLN and HAL (68.7% v 71.8%; P = .78). In the acute period (day 1) and the delayed period (days 2 to 5), CNP was similar between OLN and HAL (acute: 84.3% v 81.2%; delayed: 68.7% v 75%). No difference was identified in the rate of CEP during the overall period (81.2% with OLN v 78.1% with HAL; P = .75), during the acute period (93.7% with OLN v 90.6% with HAL), or during the delayed period (84.3% with OLN v 84.3% with HAL). No difference in toxicities was noted between treatment arms. CONCLUSION In this study, HAL had comparable efficacy to OLN in the management of CINV, which suggests that it is the higher-value option in patients who receive HEC in resource-scarce countries.
penner/lgl2is required for the integrity of the photoreceptor layer in the zebrafish retina
Authors: Kujawski Satu , Sonawane Mahendra , Knust Elisabeth 
Published: April 2019

ABSTRACTThe vertebrate retina is a complex tissue built from multiple neuronal cell types, which develop from a pseudostratified neuroepithelium. These cells are arranged into a highly organized and stereotypic pattern formed by nuclear and plexiform layers. The process of lamination as well as the maturation and differentiation of photoreceptor cells rely on the establishment and maintenance of apico-basal cell polarity and formation of adhesive junctions. Defects in any of these processes can result in impaired vision and are causally related to a variety of human diseases leading to blindness. While the importance of apical polarity regulators in retinal stratification and disease is well established, little is known about the function of basal regulators in retinal development. Here, we analyzed the role of Lgl2, a basolateral polarity factor, in the zebrafish retina. Lgl2 is upregulated in photoreceptor cells and in the retinal pigment epithelium by 72 h post fertilization. In both cell types, Lgl2 is localized basolaterally. Loss of zygotic Lgl2 does not interfere with retinal lamination or photoreceptor cell polarity or maturation. However, knockdown of both maternal and zygotic Lgl2 leads to impaired cell adhesion. As a consequence, severe layering defects occur in the distal retina, manifested by a breakdown of the outer plexiform layer and the outer limiting membrane. These results define zebrafish Lgl2 as an important regulator of retinal lamination, which, given the high degree of evolutionary conservation, may be preserved in other vertebrates, including human.
Effect of Reaction Temperature and Time on the Preferential Preparation of Cage Octamer and Decamer of Ammonium-Functionalized POSSs
Authors: Matsumoto Takatoshi , Kaneko Yoshiro 
Published: April 2019

Abstract
In this study, the hydrolytic condensation of 3-(2-aminoethylamino)propyltrimethoxysilane and 3-aminopropyltrimethoxysilane was performed using aqueous trifluoromethanesulfonic acid (HOTf) as a catalyst and solvent at various setting temperatures and pressures in a Kugelrohr apparatus. The solvent evaporation time can be controlled by changing the pressure in the Kugelrohr apparatus. Ammonium-functionalized polyhedral oligomeric silsesquioxane (POSS) mixtures with high proportions of cage octamer (T8-POSS) were consequently obtained at lower setting temperatures (60 °C) in a Kugelrohr apparatus regardless of the solvent evaporation times (2–10 h). Meanwhile, using higher setting temperatures (100 °C and 120 °C) and longer solvent evaporation times (6–8 h), the proportion of cage decamer (T10-POSS) in the POSS mixture increased. Therefore, T10-POSS formed more easily than T8-POSS during reactions in which the solvent was evaporated at higher temperatures and for longer times.
A pilot study on assessing the gap between nurses’ task performances and knowledge pertaining the same with reference to “ I COUGH” initiative- a call for promoting patient ‘care bundle’ assignments in low-income nations
Authors: Munakomi Sunil , Shrestha Sangam , Luitel Anita 
Published: April 2019

Background: The health sector in low-income nations has been crippled owing to low resources, lack of trained staff and a scarcity of effective health-related reforms. Amidst such a scenario, implementation of patient-centered care bundle approaches could help reprise the autonomy and standards of care for healthcare providers as well as safeguard patient safety. Methods: We sought to determine the gap between task performance and the underlying knowledge pertaining the same among nurses from intensive and high dependency neurosurgical units within three hospitals in Nepal through a questionnaire-based approach focusing on task assignments to prevent pulmonary complications among their patients and scoring them with references to the variables of ‘I COUGH’, a similar patient care bundle initiative. Results: There is a gross discrepancy between the patterns of task performance and the knowledge regarding the rationale behind the same tasks among nurses working in critical care neurosurgical units. In reference to I COUGH, nurses had below 50% knowledge on interventions aimed to prevent pulmonary complications among their patients, irrespective of the level of experience attained in the units. Furthermore, none of them had complete knowledge regarding all components of effective chest physiotherapy. Conclusion: There is the utmost need for the implementation of patient-focused care bundle approaches in upraising the health delivery standards, especially in low-income nations. Such initiatives can promote autonomy amongst healthcare professionals on patient care as well as assuring better patient outcomes by minimizing complications.
“Why have I not been told about this?”: a survey of experiences of and attitudes to advance decision-making amongst people with bipolar
Authors: Hindley Guy , Stephenson Lucy A. , Ruck Keene Alex , Rifkin Larry , Gergel Tania , Owen Gareth 
Published: April 2019

Background: The idea that people with severe mental illness should be able to plan in advance for periods of illness as a means of enhancing autonomy has been long debated and is increasingly being enshrined in codes of practice and mental health legislation. It has been argued that the ethical imperative for this is especially pronounced in bipolar (BP), a condition in which sufferers often experience episodic crises interspersed with periods of wellness. However, there is a paucity of published research investigating experiences of advance decision making (ADM) in people with BP or their attitudes towards it. Methods: An online survey of BPUK’s mailing list was conducted. 932 people with BP completed the survey (response rate 5.61%). Descriptive statistics and regression analysis were conducted to compare experience of with attitudes towards ADM and variables associated with interest in ADM. Results: A majority indicated a desire to plan care in advance of losing capacity (88%) but most had not done so (64%). High numbers of respondents expressed a wish to request as well as refuse treatment and most wanted to collaborate with psychiatrists, including on issues around self-binding. The most frequent motivation to utilise ADM was a desire to be more involved in mental health decisions. Interest in self-binding was associated with experience of compulsory treatment and trust in mental health services. Interest in refusals of all medication was associated with younger age and lack of trust in mental health services. Interest in ADM in general was associated with younger age but not educational level, ethnicity or gender. Conclusions: This study demonstrates an appetite for ADM amongst people with bipolar that is independent of educational status and ethnicity. As states reform their mental health laws, attention needs to be given to the distinctive attitudes toward ADM amongst people with bipolar.
Dignity in life and care: the perspectives of Swedish patients in a palliative care context
Authors: Bylund-Grenklo Tove , Werkander-Harstäde Carina , Sandgren Anna , Benzein Eva , Östlund Ulrika 
Published: April 2019

Background: How patients preserve their sense of dignity in life is an important area of palliative care that remains to be explored. Aims: To describe patients' perspectives of what constitutes a dignified life within a palliative care context. Methods: Twelve palliative care patients were interviewed about their views on living with dignity. Data were analysed using qualitative content analysis. Results: What constitutes a dignified life during end-of-life care was captured by the theme ‘I may be ill but I am still a human being’ and presented under the categories ‘preserving my everyday life and personhood’, ‘having my human value maintained by others through ‘coherence’ and ‘being supported by society at large’. Conclusion: Patients' sense of dignity can be preserved by their own attitudes and behaviours, by others and through public support. Health professionals need to adopt a dignity-conserving approach, for which awareness of their own attitudes and behaviours is crucial.
Breast Cancer Subtype Classification Using 4-Plex Droplet Digital PCR
Authors: Chen Wenwen , Zheng Jiaying , Wu Chang , Liu Shaoxiong , Chen Yongxin , Liu Xiaolei , Du Jihui , Wang Jidong 
Published: April 2019

AbstractBACKGROUNDInfiltrating ductal carcinoma (IDCA) is the most common form of invasive breast cancer. Immunohistochemistry (IHC) is widely used to analyze estrogen receptor 1 (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) that can help classify the tumor to guide the medical treatment. IHC examinations require experienced pathologists to provide interpretations that are subjective, thereby lowering the reproducibility of IHC-based diagnosis. In this study, we developed a 4-plex droplet digital PCR (ddPCR) for the simultaneous and quantitative analyses of estrogen receptor 1 (ESR1), progesterone receptor (PGR), erb-b2 receptor tyrosine kinase 2 (ERBB2), and pumilio RNA binding family member 1 (PUM1) expression levels in formalin-fixed paraffin-embedded (FFPE) samples.METHODSWe evaluated the sensitivity, reproducibility, and linear dynamic range of 4-plex ddPCR. We applied this method to analyze 95 FFPE samples from patients with breast IDCA and assessed the agreement rates between ddPCR and IHC to evaluate its potential in classifying breast cancer subtypes.RESULTSThe limits of quantification (LOQ) were 25, 50, 50, and 50 copies per reaction for ERBB2, ESR1, PGR, and PUM1, respectively. The dynamic ranges of ESR1, PGR, and PUM1 extended over 50–1600 copies per reaction and those of ERBB2 from 25 to 1600 copies per reaction. The concordance correlation coefficients between 4-plex ddPCR and IHC were 96.8%, 91.5%, and 85.1% for ERBB2, ESR1, and PGR, respectively. Receiver operating characteristic curve area under the curve values of 0.991, 0.977, and 0.920 were generated for ERBB2, ESR1, and PGR, respectively.CONCLUSIONSEvaluation of breast cancer biomarker status by 4-plex ddPCR was highly concordant with IHC in this study.