bluuebunny/crossref_metadata_2025_split huggingface dataset:
Patients with systemic sclerosis-associated pulmonary arterial hypertension express a genomic signature distinct from patients with interstitial lung disease
Authors: Moll Matthew , Christmann Romy B , Zhang Yuqing , Whitfield Michael L , Wang Yu Mei , Rice Lisa , Stratton Eric , Lafyatis Robert , Farber Harrison W 
Published: March 2018

Objective: Pulmonary arterial hypertension and interstitial lung disease are major causes of mortality in systemic sclerosis. We used a previously identified microarray biomarker to determine whether systemic sclerosis-pulmonary arterial hypertension and systemic sclerosis-interstitial lung disease patients demonstrate distinct gene expression profiles. Methods: Peripheral blood mononuclear cells were collected from healthy controls ( n = 10), systemic sclerosis patients without pulmonary hypertension (systemic sclerosis-no pulmonary arterial hypertension, n = 39), and systemic sclerosis-pulmonary arterial hypertension patients ( n = 21; mean pulmonary arterial pressure ≥25, pulmonary capillary wedge pressure ≤15, and pulmonary vascular resistance ≥3 Wood units) diagnosed by right heart catheterization. Systemic sclerosis-interstitial lung disease patients were defined as those with evidence of fibrosis on chest computed tomography and significant restriction (forced vital capacity <70% predicted, n = 11). Systemic sclerosis-pulmonary arterial hypertension biomarker included 69 genes selected by unbiased statistical screening of three publicly available microarray studies. RNA levels were measured by NanoString Technologies. Gene expression levels that were significantly correlated with pulmonary arterial hypertension (multiple statistical measures) were chosen as inputs into a forward selection logistic regression model. Results: When interstitial lung disease patients were included ( n = 64), four genes (S100P, CD8B1, CCL2, and TIMP1) and male sex predicted pulmonary arterial hypertension with a high level of accuracy (area under the curve = 0.83). Without interstitial lung disease patients ( n = 53), two genes (THBS1 and CD8B1) and male sex predicted pulmonary arterial hypertension with a high level of accuracy (area under the curve = 0.80). When examining systemic sclerosis patients with borderline elevated pulmonary pressures (mean pulmonary arterial pressure = 21–24 mmHg), gene expression changes closely resembled the systemic sclerosis-pulmonary arterial hypertension group, except for THBS1. Conclusion: Systemic sclerosis-pulmonary arterial hypertension and systemic sclerosis-interstitial lung disease have similar but distinct gene expression profiles. Many gene expression changes occur early in the disease course, potentially allowing early detection. THBS1 appears to be an important mediator in the development of pulmonary arterial hypertension-predominant phenotype. Further prospective investigation is warranted.
Fe-, Fe,Mn- and Fe,Mg-chlorite: a genetic linkage to W, (Cu,Mo) mineralization in the magmatic-hydrothermal system at Borralha, northern Portugal
Authors: Bobos I. , Noronha F. , Mateus A. 
Published: March 2018

ABSTRACTA genetic linkage between W, (Cu, Mo)-mineralization and chlorite minerals, and the discrimination of different mineralization events in the magmatic-hydrothermal system of Borralha, northern Portugal, is discussed on the basis of textural relationships, crystal chemistry and stable isotopic data obtained from chlorite. Chlorite minerals were identified in assemblages with quartz, feldspars, tungstates and sulfides. X-ray diffraction studies of selected chlorite minerals shows a trioctahedral structural type. Electron probe micro-analyses identified four different compositions and associations: (1) Fe,Mn-chlorite with scheelite I; (2) Fe-chlorite with wolframite + scheelite II ± sulfide; (3) Fe,Mg-chlorite with molybdenite + bismuthinite; and (4) Mg,Fe-chlorite with chalcopyrite. The composition of Fe-chlorite (Al3.01Fe3+0.25Fe2+7.95Mn0.26Mg0.19)11.66(Si5.44Al2.56)8O20(OH)8corresponds to daphnite and Fe,Mn-chlorite (Al2.69Fe3+0.02Fe2+7.54Mn1.08Mg0.62)11.89(Si5.31Al2.68)4O20(OH)8to a mixed composition between daphnite and amesite. The Fe,Mg-chlorite (Al2.89Fe3+0.24Fe2+6.42Mn0.21Mg2.08)11.84(Si5.31Al2.79)8F0.31O20(OH)8corresponds to ripidolite and Mg,Fe-chlorite (Al2.63Fe3+0.37Fe2+1.72Mn0.01Mg6.40Ca0.26)11.39(Si6.02Al1.98)8O20(OH)8to pychnochlorite.Chlorite geothermometry estimates a temperature for Fe,Mn-chlorite (scheelite I) from 400°C to 500°C, for Fe-chlorite (Mn-rich wolframite + scheelite II ± sulfide) from 250 to 350°C, for Fe,Mg-chlorite (Mo-mineralization) from 200°C to 250°C and for Mg,Fe-chlorite at ~150°C. Oxygen isotopes (V-SMOW) yielded values of +3.8 (1σ) (Fe-chlorite), +6.91 (1σ) (Fe,Mn-chlorite) and +1.5 (1σ) (Fe,Mg-chlorite). The calculated δ18OFof Fe- and Fe,Mg-chlorite is ~+3.75 (1σ) and +1.45 (1σ) for the mineralizing fluid, whereas for Fe,Mn-chlorite it is +8.17 (1σ). The δ18O data obtained from quartz in W- and Mo-mineralization yielded values of +12.6 and +11.4 (1σ), whereas for adularia δ18O is about +10 (1σ). These estimates allow us to conclude that the Fe,Mn-chlorite crystallized from a magmatic-hydrothermal fluid, whereas the Fe- and Fe,Mg-chlorite quartz and adularia resulted from a mixed contribution between meteoric and magmatic-hydrothermal fluid.
Mechanisms of resistance to EZH2 inhibitors in diffuse large B-cell lymphomas
Authors: Bisserier Malik , Wajapeyee Narendra 
Published: March 2018

Key Points
Resistance to EZH2 inhibitors occurs due to the activation of survival pathways and acquired EZH2 mutations that prevent drug binding. Resistance mechanisms for different EZH2 inhibitors varies. Thus, cells resistant to 1 EZH2 inhibitor are sensitive to other inhibitors.
Preclinical evaluation of NUDT15-guided thiopurine therapy and its effects on toxicity and antileukemic efficacy
Authors: Nishii Rina , Moriyama Takaya , Janke Laura J. , Yang Wenjian , Suiter Chase C. , Lin Ting-Nien , Li Lie , Kihira Kentaro , Toyoda Hidemi , Hofmann Ute , Schwab Matthias , Takagi Masatoshi , Morio Tomohiro , Manabe Atsushi , Kham Shirley , Jiang Nan , Rabin Karen R. , Kato Motohiro , Koh Katsuyoshi , Yeoh Allen Eng-Juh , Hori Hiroki , Yang Jun J. 
Published: March 2018

Key Points
We established a Nudt15 knockout mouse model with which to evaluate individualized thiopurine therapy. Preemptive NUDT15 genotype–guided thiopurine dosing can effectively prevent drug toxicity without compromising antileukemic efficacy.
The identification of fibrosis-driving myofibroblast precursors reveals new therapeutic avenues in myelofibrosis
Authors: Kramann Rafael , Schneider Rebekka K. 
Published: March 2018

AbstractMyofibroblasts are fibrosis-driving cells and are well characterized in solid organ fibrosis, but their role and cellular origin in bone marrow fibrosis remains obscure. Recent work has demonstrated that Gli1+ and LepR+ mesenchymal stromal cells (MSCs) are progenitors of fibrosis-causing myofibroblasts in the bone marrow. Genetic ablation of Gli1+ MSCs or pharmacologic targeting of hedgehog (Hh)-Gli signaling ameliorated fibrosis in mouse models of myelofibrosis (MF). Moreover, pharmacologic or genetic intervention in platelet-derived growth factor receptor α (Pdgfrα) signaling in Lepr+ stromal cells suppressed their expansion and ameliorated MF. Improved understanding of cellular and molecular mechanisms in the hematopoietic stem cell niche that govern the transition of MSCs to myofibroblasts and myofibroblast expansion in MF has led to new paradigms in the pathogenesis and treatment of MF. Here, we highlight the central role of malignant hematopoietic clone-derived megakaryocytes in reprogramming the hematopoietic stem cell niche in MF with potential detrimental consequences for hematopoietic reconstitution after allogenic stem cell transplantation, so far the only therapeutic approach in MF considered to be curative. We and others have reported that targeting Hh-Gli signaling is a therapeutic strategy in solid organ fibrosis. Data indicate that targeting Gli proteins directly inhibits Gli1+ cell proliferation and myofibroblast differentiation, which results in reduced fibrosis severity and improved organ function. Although canonical Hh inhibition (eg, smoothened [Smo] inhibition) failed to improve pulmonary fibrosis, kidney fibrosis, or MF, the direct inhibition of Gli proteins ameliorated fibrosis. Therefore, targeting Gli proteins directly might be an interesting and novel therapeutic approach in MF.
Impact of GI Tumor Board on Patient Management and Adherence to Guidelines
Authors: AlFarhan Haneen A. , Algwaiz Ghada F. , Alzahrani Hajer A. , Alsuhaibani Roaa S. , Alolayan Ashwaq , Abdelhafiz Nafisa , Ali Yosra , Boghdadly Sami , Jazieh Abdul Rahman 
Published: March 2018

Purpose As the burden of cancer on the population and the health care system continues to increase with more complicated treatment options, the need for multidisciplinary teams to be as efficient as possible becomes more vital. Our study aimed to evaluate the consistency of GI Tumor Board (GI TB) recommendations with international guidelines, the adherence of physicians involved in patient care to TB recommendations, and the impact on the management of patients. Methods A prospective cohort study was conducted from January to June 2016 at our institution, which is a major tertiary hospital that provides comprehensive cancer care. All cases presented at the GI TB during this period were included. Data regarding adherence to National Comprehensive Cancer Network guidelines, adherence to TB recommendations, and changes made to the management of patients were collected weekly from the GI TB in a data collection form. Results Of the 104 patients included, 57 (55%) were males and the median age was 58 (16 to 85) years. Colorectal cancer was the most common diagnosis, in 65 patients (63%). Nearly one-half of cases (45%) were stage IV cancers. Starting new treatment was recommended for 72 patients (69%). Further investigations were requested for 15 patients (14%). For imaging, 24 recommendations (23%) were made. Adherence to National Comprehensive Cancer Network guidelines was observed in 97% of total recommendations. New findings were found in pathology (11%), radiology (13%), and staging (4%). Management plans were changed in 37 cases (36%). Over a 3-month period after presentation to the GI TB, most of the recommendations (87%) were performed. Conclusion A multidisciplinary tumor board enhances the adherence to guidelines and has an impact on patient management in approximately one-third of patients. Among physicians, adherence to recommendations of the TB was high.
IV steroids during long episodes of Kleine-Levin syndrome
Authors: Léotard Antoine , Groos Elisabeth , Chaumereuil Charlotte , Peter-Derex Laure , Rossetti Andrea O. , Leu-Semenescu Smaranda , Arnulf Isabelle 
Published: March 2018

ObjectiveTo retrospectively compare the benefits (episode cessation) and risks of IV methylprednisolone (IV-MP) vs abstention during prolonged Kleine-Levin syndrome (KLS) episodes.MethodsA total of 26 patients with KLS received 1 g/d IV-MP for 3 days during 1 to 6 episodes each (totaling 43 IV-MP sessions). The change of episode duration with IV-MP (vs previous episode duration) was compared with the change duration between 2 consecutive episodes in 48 untreated patients matched for age, sex, age at KLS onset, number of episodes, and disease duration (more treated than untreated patients had long episodes).ResultsEleven patients (42.3%) had an episode that was at least 1 week shorter than the preceding one when they received IV-MP therapy, whereas shorter episodes were significantly less frequent (10.4%) in the untreated group. This benefit was more marked (65.5% responders, 12 fewer days in an episode vs 0 days in the untreated patients) when IV-MP was infused before the 10th day of the episode. Mild, transient adverse effects (insomnia, muscle pain, nervousness/restlessness, but no manic switching) were reported by 61.3% of patients. No specific responder profile was identified.ConclusionIn this open-labeled, naturalistic study, early IV-MP (following the protocol for multiple sclerosis relapses) had a good benefit/risk ratio during KLS episodes in patients with long episodes (with half of the patients having an early cessation of episodes).Classification of evidenceThis study provides Class IV evidence that for patients with long episodes of KLS, IV steroids decrease the duration of KLS episodes.
Cerebellar volume as an imaging marker of development in infants with tuberous sclerosis complex
Authors: Srivastava Siddharth , Prohl Anna K. , Scherrer Benoit , Kapur Kush , Krueger Darcy A. , Warfield Simon K. , Sahin Mustafa ,   On behalf of the TACERN Study Group
Published: March 2018

ObjectiveIn this cohort analysis, we studied 1-year-old infants with tuberous sclerosis complex (TSC), correlating volumes of cerebellar structures with neurodevelopmental measures.MethodsWe analyzed data from a prospective biomarker study in infants with TSC (ClinicalTrials.govNCT01780441). We included participants aged 12 months with an identified mutation of TSC1 or TSC2. Using MRI segmentation performed with the PSTAPLE algorithm, we measured relative volumes (structure volume divided by intracranial contents volume) of the following structures: right/left cerebellar white matter, right/left cerebellar exterior, vermal lobules I–V, vermal lobules VI–VII, and vermal lobules VIII–X. We correlated relative volumes to Mullen Scales of Early Learning (MSEL) scores.ResultsThere were 70 participants (mean age 1.03 [0.11] years): n = 11 had a TSC1 mutation; n = 59 had a TSC2 mutation. For patients with TSC2 mutation, for every percentage increase in total cerebellar volume, there was an approximate 10-point increase in MSEL composite score (β = 10.47 [95% confidence interval 5.67, 15.27], p < 0.001). For patients with TSC1 mutation, the relationship between cerebellar volume and MSEL composite score was not statistically significant (β = −10.88 [95% confidence interval −22.16, 0.41], p = 0.06). For patients with TSC2 mutation, there were positive slopes when regressing expressive language and visual reception skills with volumes of nearly all cerebellar structures (p ≤ 0.29); there were also positive slopes when regressing receptive language skills, gross motor skills, and fine motor skills with volumes of cerebellar right/left exterior (p ≤ 0.014).ConclusionsCerebellar volume loss—perhaps reflecting Purkinje cell degeneration—may predict neurodevelopmental severity in patients with TSC2 mutations.
White matter abnormalities and cognition in patients with conflicting diagnoses and CSF profiles
Authors: Lindemer Emily R. , Greve Douglas N. , Fischl Bruce , Salat David H. , Gomez-Isla Teresa 
Published: March 2018

ObjectiveTo determine whether white matter changes influence progression of cognitive decline in individuals with clinically diagnosed Alzheimer disease (AD) and differing biomarker profiles.MethodsTwo hundred thirty-six individuals from the Alzheimer's Disease Neuroimaging Initiative database with clinical diagnoses of cognitively normal older adult (older controls [OCs]), mild cognitive impairment, and AD were studied. Support vector machine experiments were first performed to determine the utility of various biomarkers for classifying individuals by clinical diagnosis. General linear models were implemented to assess the relationships between CSF measures of β-amyloid 1–42, phosphorylated tau181p, and MRI-based white matter signal abnormality (WMSA) volumes and cognitive decline. Analyses were performed across all patients as well as within subgroups of individuals that were defined by clinical cutoff points for both CSF measures.ResultsCSF biomarkers alone classified individuals with AD vs OCs with 82% accuracy, and the addition of WMSA did not enhance this. Both CSF biomarkers as well as WMSA volume significantly contributed to predicting cognitive decline in executive and memory domains when assessed across all 236 individuals. In individuals with pathologic levels of both CSF biomarkers, WMSA only significantly contributed to models of future executive function decline. In individuals with subpathologic CSF biomarker levels (levels similar to those in OC individuals), WMSA significantly contributed to prediction of memory decline and were the sole significant predictor of executive function decline.ConclusionsWMSA hold additional predictive power regarding cognitive progression in older individuals and are most effective as biomarkers in individuals who are cognitively impaired but do not fit the expected CSF biomarker profile of AD.
Efficacy of Exercise and Testosterone to Mitigate Atrophic Cardiovascular Remodeling
Authors: SCOTT JESSICA M. , MARTIN DAVID , PLOUTZ-SNYDER ROBERT , DOWNS MEGHAN , DILLON E. LICHAR , SHEFFIELD-MOORE MELINDA , URBAN RANDALL J. , PLOUTZ-SNYDER LORI L. 
Published: March 2018

ABSTRACT

Purpose
Early and consistent evaluation of cardiac morphology and function throughout an atrophic stimulus is critically important for the design and optimization of interventions. This randomized controlled trial was designed 1) to characterize the time course of unloading-induced morphofunctional remodeling and 2) to examine the effects of exercise with and without low-dose testosterone supplementation on cardiac biomarker, structural, and functional parameters during unloading.

Methods
Twenty-six subjects completed 70 d of head-down tilt bed rest (BR): 9 were randomized to exercise training (Ex), 8 to EX and low-dose testosterone (ExT), and 9 remained sedentary (CONT). Exercise consisted of high-intensity, continuous, and resistance exercise. Cardiac morphology (left ventricular mass [LVM]) and mechanics (longitudinal, radial, and circumferential strain and twist), cardiovascular biomarkers, and cardiorespiratory fitness (V˙O2peak) were assessed before, during, and after BR.

Results
Sedentary BR resulted in a progressive decline in LVM, longitudinal, radial, and circumferential strain in CONT, whereas Ex and ExT mitigated decreases in LVM and function. Twist was increased throughout BR in sedentary BR, whereas after an initial increase at BR7, there were no further changes in twist in Ex and ExT. HDL cholesterol was significantly decreased in all groups compared with pre-BR (P < 0.007). There were no significant changes in other cardiovascular biomarkers. Change in twist was significantly related to change in V˙O2max (R = 0.68, P < 0.01).

Conclusion
An integrated approach with evaluation of cardiac morphology, mechanics, V˙O2peak, and biomarkers provides extensive phenotyping of cardiovascular atrophic remodeling. Exercise training and exercise training with low-dose testosterone supplementation abrogates atrophic remodeling.
Microwave disinfection as a treatment for blackwater from dewatered sludge
Authors: Sellgren Katelyn L , Gregory Christopher W , Klem Ethan J.D. , Piascik Jeffrey R. , Stoner Brian R. 
Published: March 2018

Background: Fast and efficient on-site treatment of blackwater, rejected from the dewatering process, can decrease the costs associated with disposal of fecal sludge removed from pit latrines by reducing the volume of sludge transported to the disposal site.Methods: In this study, we examine the potential use of low cost consumer microwave units for disinfecting pathogen-rich blackwater. Domestic bench top microwave units were modified to allow flow through and re-circulation of blackwater. Energy, throughput, and disinfection characteristics related to microwaves are studied and compared to conventional thermal heating. A custom flow through stack of 5 microwaves was designed and used to examine the feasibility of single pass, high throughput application.Results and Conclusions: The results show microwave energy does not play a role in the disinfection of blackwater. The benefits of a microwave disinfection system are shown to be high energy efficiency, compact size, and cost efficiency.
Syberia w pamięci zesłańców i ich dzieci
Authors: Abassy Małgorzata 
Published: March 2018

Syberia in the Memories of the Polish Exiles. Case Study of the Zhukovsky Family
The story of the exiles of the Zhukovsky family is presented in the paper. Analyses were based on interviews with Dagmara, the daughter, two documentaries: On memory paths and Crust of Bread, and a manuscript written on the basis of Danuta and Bogusław recollections by Dagmara. Hypotheses of the paper were the following: a story of a family is the history of a nation. There is a parallel between historical events and an individual’s fate. The ancestors, need to tell one’s story and the descendants’ need to hear it are reciprocal ones and can be interpreted as a cultural mechanism of incorporation new texts into a culture memory. On an individual level it gives rise to the feeling of dignity and power. Marianne Hirsch’s theory of post‑memory and Yury Lotman’s concept of ‘remembering – forgetting’ mechanism were utilized to present and interpret memories of Boguslav and Danuta Zhukovsky and their descendant – Dagmara. The reasons for reaching into the past and coming back to Syberia were also analysed.
Buckling down on torus fractures: Has evolving evidence affected practice?
Authors: Williams B. A. , Alvarado C. A. , Montoya-Williams D. C. , Matthias R. C. , Blakemore L. C. 
Published: March 2018

Purpose The purpose of this study was to evaluate the management of paediatric torus fractures of the distal forearm in current practice in light of growing evidence supporting a ‘minimalist’ approach with splint immobilization and limited follow-up. We hypothesized that ‘traditional’ cast-based management has persisted despite alternative evidence. Methods A retrospective review was performed of a consecutive series of paediatric patients diagnosed with torus fractures of the distal forearm between 2011 and 2014. Records were reviewed to abstract the type of immobilization (splint versus cast) prescribed at each visit, number of radiographic exams, duration of immobilization, number of clinical visits and complications. The primary outcome was the proportion of patients exclusively managed in splints. Injuries were grouped based on treatment into a cast group (CG) and a splint group (SG) for statistical analyses. Additionally, injuries were grouped by epoch of time to determine if immobilization usage patterns evolved. Results A total of 240 forty injuries met criteria for inclusion. Of these, 16 (6.7%) were exclusively splinted (SG). Relative to the CG, the SG had fewer clinical visits (p < 0.001), fewer radiographic exams (p < 0.001) and a shorter total encounter time (p = 0.015). No change in immobilization use occurred over the study period. In all, 21 (9.4%) of the CG experienced complications. No clinically significant displacements occurred in either group. Conclusion Cast utilization and frequent radiographic follow-up remain prevalent at our institution in the management of paediatric torus fractures. Splint-only management was associated with fewer clinical visits, fewer radiographic exams and a shorter total encounter time. Level of Evidence Level III Therapeutic retrospective cohort study