bluuebunny/crossref_metadata_2025_split huggingface dataset:
¡Activate Ya! Co-learning about school-based tobacco prevention and physical activity promotion in secondary school students in Uruguay
Authors: Springer Andrew E. , Harrell Melissa B. , Martínez Gomensoro Lucía , Traversa Fresco María , Rogers Shannon , Florines Martina , Moreno Viviana , Lee Joowon , Perry Cheryl L. , Bianco Eduardo , Estol Diego 
Published: April 2019

Purpose: ¡Activate Ya! was a group-randomized controlled intervention trial aimed at developing and evaluating the impact of a school-based intervention on preventing cigarette smoking and promoting physical activity (PA) in secondary school students in Uruguay. Secondary aims were to evaluate the program’s impact on students’ smoking- and PA-related psychosocial risk and protective factors. Methods: Sixteen schools and n = 654 students participated in the study. The one-year intervention included a classroom-based curriculum, an afterschool program, activity breaks, and final showcase event. A self-administered questionnaire measured outcomes at three time points. Fixed effects regression models tested for differences in outcomes by study condition. Results: While positive intervention effects were found for selected psychosocial-related smoking outcomes, no impact on past-year smoking or smoking susceptibility was detected. Past 7-day PA, measured by the PAQ-C, was significantly higher among intervention school students overall ( p = .048) and for girls ( p = .03) at posttest, and intervention girls reported significantly higher athletic identity PA competence, friend and teacher PA support at posttest, and PA enjoyment at follow-up ( p < .05). Conclusion: The positive short-term effects of ¡Activate Ya! on PA and related outcomes for girls support the utility of school-based health promotion in Uruguay. Additional research is needed to determine the most effective strategies to prevent tobacco use among students and promote PA among boys in this setting.
Acute adrenal haemorrhage in two cats with aldosterone-secreting adenocarcinomas
Authors: Kirkwood Nicolle , Boland Lara , Brunel Laurencie , Wardman Alison , Barrs Vanessa R 
Published: April 2019

Case summary Two 13-year-old domestic shorthair cats were diagnosed with unilateral right adrenocortical carcinomas (ACCs) and primary hyperaldosteronism (PHA). Both had polyuria, polydipsia and weight loss, and developed severe anaemia from an episode of acute adrenal haemorrhage. In one case, this occurred during hospitalisation and treatment of severe muscle weakness with cervical ventroflexion, while the other cat had acute collapse at home. A diagnosis of PHA was confirmed in both cases based on measurement of plasma aldosterone and renin activity. In one case, basal progesterone was also measured and was elevated. On ultrasonography and CT in one case, haemorrhage into the right retroperitoneal space was identified. Unilateral adrenalectomy was performed in both cases and there was no evidence of venous tumoral invasion in either. On histopathology of the excised adrenal glands both were ACCs with tumour necrosis, and one had extensive intratumoral haemorrhage. Both cats were diagnosed with International Renal Interest Society stage 2 or 3 chronic kidney disease postoperatively; one survived for 18 months and the other was well 8 months postoperatively. Relevance and novel information Acute adrenal haemorrhage secondary to adrenal neoplasia has been reported in only one other cat, in which tumour type and function were not specified. Acute adrenal haemorrhage can occur as a consequence of tumour necrosis and rupture and can cause severe hypovolaemia and anaemia in cats with primary hyperaldosteronism.
NUP98-HBO1–fusion generates phenotypically and genetically relevant chronic myelomonocytic leukemia pathogenesis
Authors: Hayashi Yoshihiro , Harada Yuka , Kagiyama Yuki , Nishikawa Sayuri , Ding Ye , Imagawa Jun , Shingai Naoki , Kato Naoko , Kitaura Jiro , Hokaiwado Shintaro , Maemoto Yuki , Ito Akihiro , Matsui Hirotaka , Kitabayashi Issay , Iwama Atsushi , Komatsu Norio , Kitamura Toshio , Harada Hironori 
Published: April 2019

Abstract
Chronic myelomonocytic leukemia (CMML) constitutes a hematopoietic stem cell (HSC) disorder characterized by prominent monocytosis and myelodysplasia. Although genome sequencing has revealed the CMML mutation profile, the mechanism of disease development remains unclear. Here we show that aberrant histone acetylation by nucleoporin-98 (NUP98)-HBO1, a newly identified fusion in a patient with CMML, is sufficient to generate clinically relevant CMML pathogenesis. Overexpression of NUP98-HBO1 in murine HSC/progenitors (HSC/Ps) induced diverse CMML phenotypes, such as severe leukocytosis, increased CD115+ Ly6Chigh monocytes (an equivalent subpopulation to human classical CD14+ CD16− monocytes), macrocytic anemia, thrombocytopenia, megakaryocyte-lineage dysplasia, splenomegaly, and cachexia. A NUP98-HBO1–mediated transcriptional signature in human CD34+ cells was specifically activated in HSC/Ps from a CMML patient cohort. Besides critical determinants of monocytic cell fate choice in HSC/Ps, an oncogenic HOXA9 signature was significantly activated by NUP98-HBO1 fusion through aberrant histone acetylation. Increased HOXA9 gene expression level with disease progression was confirmed in our CMML cohort. Genetic disruption of NUP98-HBO1 histone acetyltransferase activity abrogated its leukemogenic potential and disease development in human cells and a mouse model. Furthermore, treatment of azacytidine was effective in our CMML mice. The recapitulation of CMML clinical phenotypes and gene expression profile by the HBO1 fusion suggests our new model as a useful platform for elucidating the central downstream mediators underlying diverse CMML-related mutations and testing multiple compounds, providing novel therapeutic potential.
Vitamin D3 supplementation and treatment outcomes in patients with depression (D3-vit-dep)
Authors: Hansen Jens Peter , Pareek Manan , Hvolby Allan , Schmedes Anne , Toft Tomas , Dahl Erik , Nielsen Connie Thurøe 
Published: April 2019

Abstract
Objective
To examine whether vitamin D supplementation in patients with depression would result in a reduction in Hamilton D-17 depression score (primary outcome) at 3 and 6 months compared to controls and to explore the correlations between serum vitamin D and symptoms of depression, wellbeing, systolic blood pressure, and waist circumference. In this outpatient multicentre study conducted between 2010 and 2013, patients, 18–65 years old, diagnosed with mild to severe depression were randomly assigned to receive D supplementation 70 micrograms daily or placebo on top of standard treatment. Participants, care givers and those assessing the outcomes were blinded to group assignment.

Results
At baseline, 23 patients had a normal 25(OH)D level, 22 had insufficiency (< 25 nmol/L), and 17 had deficiency (25–50 nmol/L). No significant reduction in depression was seen after vitamin D supplementation compared to placebo at Hamilton (18.4–18.0; p = 0.73 at 12 weeks). Vitamin D supplementation did not provide a reduction in symptom score among patients with depression.
Trial registration The trial was registered in the National Board of Health (EudraCT: 2011-002585-20) and in ClinicalTrials.Gov (NCT01390662).
Omalizumab in patients with severe asthma and persistent sputum eosinophilia
Authors: Mukherjee Manali , Kjarsgaard Melanie , Radford Katherine , Huang Chynna , Leigh Richard , Dorscheid Delbert R. , Lemiere Catherine , Boulet Louis-Philippe , Waserman Susan , Martin James , Nair Parameswaran 
Published: April 2019

AbstractOmalizumab, a recombinant humanized monoclonal antibody targeting the IgE molecule, is the first biologic approved for moderate-to-severe allergic asthmatics, who remain uncontrolled despite high dose inhaled corticosteroid and bronchodilators. Steroid-sparing effect of omalizumab has not been demonstrated in asthmatics with persistent airway eosinophilia in a randomised controlled trial till date. From this double-blind, placebo-controlled, multi-centred, randomized parallel group design, we report that omalizumab is possibly inadequate to control sputum eosinophilia, and therefore may not have a steroid-sparing effect, especially in those maintained on oral corticosteroids daily. This needs to be confirmed or refuted in a larger trial, which may be a challenge with respect to recruitment, since there are currently three additional biologics available to prescribe.Trial registration Clinicaltrials.gov, NCT02049294, Registered 30th January 2014, https://clinicaltrials.gov/ct2/show/NCT02049294
Safety and Efficacy of a Five-Fraction Stereotactic Body Radiotherapy Schedule for Centrally Located Non–Small-Cell Lung Cancer: NRG Oncology/RTOG 0813 Trial
Authors: Bezjak Andrea , Paulus Rebecca , Gaspar Laurie E. , Timmerman Robert D. , Straube William L. , Ryan William F. , Garces Yolanda I. , Pu Anthony T. , Singh Anurag K. , Videtic Gregory M. , McGarry Ronald C. , Iyengar Puneeth , Pantarotto Jason R. , Urbanic James J. , Sun Alexander Y. , Daly Megan E. , Grills Inga S. , Sperduto Paul , Normolle Daniel P. , Bradley Jeffrey D. , Choy Hak 
Published: April 2019

PURPOSE Patients with centrally located early-stage non–small-cell lung cancer (NSCLC) are at a higher risk of toxicity from high-dose ablative radiotherapy. NRG Oncology/RTOG 0813 was a phase I/II study designed to determine the maximum tolerated dose (MTD), efficacy, and toxicity of stereotactic body radiotherapy (SBRT) for centrally located NSCLC. MATERIALS AND METHODS Medically inoperable patients with biopsy-proven, positron emission tomography–staged T1 to 2 (≤ 5 cm) N0M0 centrally located NSCLC were accrued into a dose-escalating, five-fraction SBRT schedule that ranged from 10 to 12 Gy/fraction (fx) delivered over 1.5 to 2 weeks. Dose-limiting toxicity (DLT) was defined as any treatment-related grade 3 or worse predefined toxicity that occurred within the first year. MTD was defined as the SBRT dose at which the probability of DLT was closest to 20% without exceeding it. RESULTS One hundred twenty patients were accrued between February 2009 and September 2013. Patients were elderly, there were slightly more females, and the majority had a performance status of 0 to 1. Most cancers were T1 (65%) and squamous cell (45%). Organs closest to planning target volume/most at risk were the main bronchus and large vessels. Median follow-up was 37.9 months. Five patients experienced DLTs; MTD was 12.0 Gy/fx, which had a probability of a DLT of 7.2% (95% CI, 2.8% to 14.5%). Two-year rates for the 71 evaluable patients in the 11.5 and 12.0 Gy/fx cohorts were local control, 89.4% (90% CI, 81.6% to 97.4%) and 87.9% (90% CI, 78.8% to 97.0%); overall survival, 67.9% (95% CI, 50.4% to 80.3%) and 72.7% (95% CI, 54.1% to 84.8%); and progression-free survival, 52.2% (95% CI, 35.3% to 66.6%) and 54.5% (95% CI, 36.3% to 69.6%), respectively. CONCLUSION The MTD for this study was 12.0 Gy/fx; it was associated with 7.2% DLTs and high rates of tumor control. Outcomes in this medically inoperable group of mostly elderly patients with comorbidities were comparable with that of patients with peripheral early-stage tumors.
Transcriptome Analyses Identify a Metabolic Gene Signature Indicative of Dedifferentiation of Papillary Thyroid Cancer
Authors: Ma Ben , Jiang Hongyi , Wen Duo , Hu Jiaqian , Han Litao , Liu Wanlin , Xu Weibo , Shi Xiao , Wei Wenjun , Liao Tian , Wang Yulong , Lu Zhongwu , Wang Yu , Ji Qinghai 
Published: April 2019

Abstract

Context
Metabolic reprogramming is a common feature of tumorigenesis. It remains unknown concerning the expression pattern of metabolism-associated genes in dedifferentiated thyroid cancer (DDTC).

Objective
This study aimed to identify a useful signature to indicate dedifferentiation of papillary thyroid cancer (PTC).

Design and Setting
We used one discovery and two validation cohorts to screen out aberrant metabolic genes in DDTC, and further used The Cancer Genome Atlas (TCGA) cohort to search for independent risk factors for the low-differentiated phenotype of PTC as a signature of dedifferentiation. The prediction of the signature for DDTC was validated in the TCGA cohort and the combined Gene Expression Omnibus cohort. We also analyzed the correlations of the signature risk score with clinicopathological features of PTC. Gene set enrichment analyses were performed in the TCGA cohort.

Results
Significant enrichment of metabolic pathways correlated with differentiation status of PTC. A signature of metabolic genes including LPCAT2, ACOT7, HSD17B8, PDE8B, and ST3GAL1 was discovered and validated across three cohorts. The signature was not only predictive of DDTC but also significantly associated with BRAFV600E mutation (P < 0.001), T3/T4 stage (P < 0.001), extrathyroidal extension (P < 0.001), lymph node metastasis (P < 0.001), and tumor/lymph node/metastasis III/IV stage (P < 0.001) in PTC. Downregulations of LPCAT2 expression (P = 0.009) and ST3GAL1 expression (P = 0.005) increased risks of decreased disease-free survival for patients. Furthermore, the signature was implicated in a number of oncogenic biological pathways.

Conclusions
Our findings suggest that metabolic deregulations mediate dedifferentiation of PTC, and that the metabolic gene signature can be used as a biomarker for DDTC.
Influences of Hypoxia Exercise on Whole-Body Insulin Sensitivity and Oxidative Metabolism in Older Individuals
Authors: Chobanyan-Jürgens Kristine , Scheibe Renate J , Potthast Arne B , Hein Markus , Smith Andrea , Freund Robert , Tegtbur Uwe , Das Anibh M , Engeli Stefan , Jordan Jens , Haufe Sven 
Published: April 2019

Abstract

Context
Aging is a primary risk factor for most chronic diseases, including type 2 diabetes. Both exercise and hypoxia regulate pathways that ameliorate age-associated metabolic muscle dysfunction.

Objective
We hypothesized that the combination of hypoxia and exercise would be more effective in improving glucose metabolism than normoxia exercise.

Design and Participants
We randomized 29 older sedentary individuals (62 ± 6 years; 14 women, 15 men) to bicycle exercise under normobaric hypoxia (fraction of inspired oxygen = 15%) or normoxia (fraction of inspired oxygen = 21%).

Intervention
Participants trained thrice weekly for 30 to 40 minutes over 8 weeks at a heart rate corresponding to 60% to 70% of peak oxygen update.

Main Outcome Measures
Insulin sensitivity measured by hyperinsulinemic-euglycemic glucose clamp and muscle protein expression before and after hyperinsulinemic-euglycemic glucose clamp.

Results
Heart rate and perceived exertion during training were similar between groups, with lower oxygen saturation when exercising under hypoxia (88.7 ± 1.5 vs 96.2 ± 1.2%, P < 0.01). Glucose infusion rate after 8 weeks increased in both the hypoxia (5.7 ± 1.1 to 6.7 ± 1.3 mg/min/kg; P < 0.01) and the normoxia group (6.2 ± 2.1 to 6.8 ± 2.1 mg/min/kg; P = 0.04), with a mean difference between groups of –0.44 mg/min/kg; 95% CI, –1.22 to 0.34; (P = 0.25). Markers of mitochondrial content and oxidative capacity in skeletal muscle were similar after training in both groups. Changes in Akt phosphorylation and glucose transporter 4 under fasting and insulin-stimulated conditions were not different between groups over time.

Conclusions
Eight weeks of hypoxia endurance training led to similar changes in insulin sensitivity and markers of oxidative metabolism compared with normoxia training. Normobaric hypoxia exercise did not enhance metabolic effects in sedentary older women and men beyond exercise alone.
Bacterial mechanosensing: the force will be with you, always
Authors: Gordon Vernita D. , Wang Liyun 
Published: April 2019

ABSTRACT
Whether bacteria are in the planktonic state, free-swimming or free-floating in liquid, or in the biofilm state, sessile on surfaces, they are always subject to mechanical forces. The long, successful evolutionary history of bacteria implies that they are capable of adapting to varied mechanical forces, and probably even actively respond to mechanical cues in their changing environments. However, the sensing of mechanical cues by bacteria, or bacterial mechanosensing, has been under-investigated. This leaves the mechanisms underlying how bacteria perceive and respond to mechanical cues largely unknown. In this Review, we first examine the surface-associated behavior of bacteria, outline the clear evidence for bacterial mechanosensing and summarize the role of flagella, type-IV pili, and envelope proteins as potential mechanosensors, before presenting indirect evidence for mechanosensing in bacteria. The general themes underlying bacterial mechanosensing that we highlight here may provide a framework for future research.
Motor control of an insect leg during level and incline walking
Authors: Dallmann Chris J. , Dürr Volker , Schmitz Josef 
Published: April 2019

ABSTRACTDuring walking, the leg motor system must continually adjust to changes in mechanical conditions, such as the inclination of the ground. To understand the underlying control, it is important to know how changes in leg muscle activity relate to leg kinematics (movements) and leg dynamics (forces, torques). Here, we studied these parameters in hindlegs of stick insects (Carausius morosus) during level and uphill/downhill (±45 deg) walking, using a combination of electromyography, 3D motion capture and ground reaction force measurements. We find that some kinematic parameters including leg joint angles and body height vary across walking conditions. However, kinematics vary little compared with dynamics: horizontal leg forces and torques at the thorax–coxa joint (leg protraction/retraction) and femur–tibia joint (leg flexion/extension) tend to be stronger during uphill walking and are reversed in sign during downhill walking. At the thorax–coxa joint, the different mechanical demands are met by adjustments in the timing and magnitude of antagonistic muscle activity. Adjustments occur primarily in the first half of stance after the touch-down of the leg. When insects transition from level to incline walking, the characteristic adjustments in muscle activity occur with the first step of the leg on the incline, but not in anticipation. Together, these findings indicate that stick insects adjust leg muscle activity on a step-by-step basis so as to maintain a similar kinematic pattern under different mechanical demands. The underlying control might rely primarily on feedback from leg proprioceptors signaling leg position and movement.
Early results and volumetric analysis after spot-scanning proton therapy with concomitant hyperthermia in large inoperable sacral chordomas
Authors: Tran Sebastien , Puric Emsad , Walser Marc , Poel Robert , Datta Niloy Ranjan , Heuberger Juerg , Pica Alessia , Marder Dietmar , Lomax Nicoletta , Bolsi Alessandra , Morach Petra , Bachtiary Barbara , Seddon Beatrice M , Schneider Ralf , Bodis Stephan , Weber Damien C 
Published: April 2019

Objective:
Large inoperable sacral chordomas show unsatisfactory local control rates even when treated with high dose proton therapy (PT). The aim of this study is assessing feasibility and reporting early results of patients treated with PT and concomitant hyperthermia (HT).

Methods:
Patients had histologically proven unresectable sacral chordomas and received 70 Gy (relative biological effectiveness) in 2.5 Gy fractions with concomitant weekly HT. Toxicity was assessed according to CTCAE_v4. A volumetric tumor response analysis was performed.

Results:
Five patients were treated with the combined approach. Median baseline tumor volume was 735 cc (range, 369–1142). All patients completed PT and received a median of 5 HT sessions (range, 2–6). Median follow-up was 18 months (range, 9–26). The volumetric analysis showed an objective response of all tumors (median shrinkage 46%; range, 9–72). All patients experienced acute Grade 2–3 local pain. One patient presented with a late Grade 3 iliac fracture.

Conclusion:
Combining PT and HT in large inoperable sacral chordomas is feasible and causes acceptable toxicity. Volumetric analysis shows promising early results, warranting confirmation in the framework of a prospective trial.

Advances in knowledge:
This is an encouraging first report of the feasibility and early results of concomitant HT and PT in treating inoperable sacral chordoma.
Early hyaluronidase use in preventing skin necrosis after treatment with dermal fillers: Report of two cases
Authors: Ciancio Francesco , Tarico Maria Stella , Giudice Giuseppe , Perrotta Rosario Emanuele 
Published: April 2019

Injection of dermal fillers, like hyaluronic acid (HA), is a safe procedure, with few and transient side effects such as erythema, bruising and swelling etc. The aim of this report is to provide our protocol for the early treatment of necrotic complications after facial treatment with dermal fillers. We present two cases of skin suffering of the face after dermal infiltration of HA, treated successfully with our early protocol. Our protocol includes the early infiltration of hyaluronidase in the treated areas. We start with infiltration of hyaluronidase distributed over the area to be treated through micro-injections with dosage 40 IU per cm2. Our protocol includes the use of systemic corticosteroids for 4 days, anti-aggregation therapy, oral antibiotic, topical cream with nitric oxide and compresses with gauze and warm water. In the skin complications after dermal filler treatment, marked pain and characteristic reticulated erythema in the skin distribution of the affected vessels is often developed. Due to the implementation of our protocol in these patients, we managed to avoid an irreversible necrotic complication of the face in both cases. In this report, our protocol was compared with results published in the literature and allowed us to avoid complications such as skin necrosis with permanent damage.
Evaluation of patient satisfaction and shade matching of Vita Suprinity versus lithium disilicate (E-max) ceramic crowns in the esthetic zone: a randomized controlled clinical trial
Authors: Abou-Steit Sameh , ElGuindy Jylan , Zaki Amina 
Published: April 2019

Background: Optical impairments of teeth in the esthetic zone constitute a problem for many dentists and patients as several studies concluded that patients were dissatisfied of their dental appearance because of their restorations' color. The purpose of this study was to assess patient satisfaction combined with shade matching of VITA SUPRINITY versus lithium disilicate (IPS e-max CAD) all-ceramic crowns in esthetic zone. Methods: 26 patients with teeth problems indicated for full coverage restoration on one tooth in the esthetic zone (from upper central incisor to 1st premolar) were randomized into 2 equal groups (n=13) for which different CAD-CAM ceramic materials were used; (VITA SUPRINITY) a zirconia reinforced lithium silicate ceramic and (IPS e.max CAD) lithium disilicate glass ceramic. The crowns were fabricated to match the shade of the contra-lateral/ adjacent tooth and assessed using the modified USPHS criteria. Also patient satisfaction was assessed. The data obtained by evaluating each assessment criteria were statistically analyzed using the Chi-square test that was performed in categorical data. Results: According to the modified USPHS criteria, 100% of the patients were Alpha score with 0% for Bravo, Charlie and Delta scores in both groups. While according to the visual analogue scale (VAS), 100% of the patients were satisfied while 0% were dissatisfied by the restoration in both groups. Conclusions: The results for both materials in terms of patient satisfaction and shade matching were Alpha. This indicated that both materials are clinically accepted to be used as full coverage restorations for excellent esthetic outcome. Registration: NCT0284611.