bluuebunny/crossref_metadata_2025_split huggingface dataset:
FDA Approval Summary: Niraparib for the Maintenance Treatment of Patients with Recurrent Ovarian Cancer in Response to Platinum-Based Chemotherapy
Authors: Ison Gwynn , Howie Lynn J. , Amiri-Kordestani Laleh , Zhang Lijun , Tang Shenghui , Sridhara Rajeshwari , Pierre Vadryn , Charlab Rosane , Ramamoorthy Anuradha , Song Pengfei , Li Fang , Yu Jingyu , Manheng Wimolnut , Palmby Todd R. , Ghosh Soma , Horne Hisani N. , Lee Eunice Y. , Philip Reena , Dave Kaushalkumar , Chen Xiao Hong , Kelly Sharon L. , Janoria Kumar G. , Banerjee Anamitro , Eradiri Okponanabofa , Dinin Jeannette , Goldberg Kirsten B. , Pierce William F. , Ibrahim Amna , Kluetz Paul G. , Blumenthal Gideon M. , Beaver Julia A. , Pazdur Richard 
Published: April 2018

Abstract
The FDA approved niraparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, on March 27, 2017, for maintenance treatment of patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in response to platinum-based chemotherapy. Approval was based on data from the NOVA trial comparing niraparib with placebo in two independent cohorts, based on germline BRCA mutation status (gBRCAm vs. non-gBRCAm). Progression-free survival (PFS) in each cohort was the primary endpoint. In the gBRCAm cohort, estimated median PFS on niraparib was 21 months versus 5.5 months on placebo [HR, 0.26; 95% confidence interval (CI), 0.17–0.41; P &lt; 0.0001]. In the non-gBRCAm cohort, estimated median PFS for niraparib and placebo was 9.3 and 3.9 months, respectively (HR, 0.45; 95% CI, 0.34–0.61; P &lt; 0.0001). Common adverse reactions (&gt;20% and higher incidence in the niraparib arm) with niraparib included thrombocytopenia, anemia, neutropenia, nausea, constipation, vomiting, mucositis, fatigue, decreased appetite, headache, insomnia, nasopharyngitis, dyspnea, rash, and hypertension. There were five cases of myelodysplastic syndrome and acute myeloid leukemia (1.4%) in patients treated with niraparib compared with two cases (1.1%) on placebo. Niraparib is the first PARP inhibitor approved as maintenance therapy for patients with ovarian, fallopian tube, or primary peritoneal cancer, with improvement in PFS, regardless of gBRCAm status. Clin Cancer Res; 24(17); 4066–71. ©2018 AACR.
See related commentary by Konstantinopoulos and Matulonis, p. 4062
Secretory IgM Exacerbates Tumor Progression by Inducing Accumulations of MDSCs in Mice
Authors: Tang Chih-Hang Anthony , Chang Shiun , Hashimoto Ayumi , Chen Yi-Ju , Kang Chang Won , Mato Anthony R. , Del Valle Juan R. , Gabrilovich Dmitry I. , Hu Chih-Chi Andrew 
Published: April 2018

AbstractChronic lymphocytic leukemia (CLL) cells can secrete immunoglobulin M. However, it is not clear whether secretory IgM (sIgM) plays a role in disease progression. We crossed the Eμ-TCL1 mouse model of CLL, in which the expression of human TCL1 oncogene was driven by the V(H) promoter-Ig(H)-Eμ enhancer, with MD4 mice whose B cells produced B-cell receptor (membrane-bound IgM) and sIgM with specificity for hen egg lysozyme (HEL). CLL cells that developed in these MD4/Eμ-TCL1 mice reactivated a parental Ig gene allele and secreted IgM, and did not recognize HEL. The MD4/Eμ-TCL1 mice had reduced survival, increased myeloid-derived suppressor cells (MDSC), and decreased numbers of T cells. We tested whether sIgM could contribute to the accumulation of MDSCs by crossing μS–/– mice, which could not produce sIgM, with Eμ-TCL1 mice. The μS–/–/Eμ-TCL1 mice survived longer than Eμ-TCL1 mice and developed decreased numbers of MDSCs which were less able to suppress proliferation of T cells. We targeted the synthesis of sIgM by deleting the function of XBP-1s and showed that targeting XBP-1s genetically or pharmacologically could lead to decreased sIgM, accompanied by decreased numbers and reduced functions of MDSCs in MD4/Eμ-TCL1 mice. Additionally, MDSCs from μS–/– mice grafted with Lewis lung carcinoma were inefficient suppressors of T cells, resulting in slower tumor growth. These results demonstrate that sIgM produced by B cells can upregulate the functions of MDSCs in tumor-bearing mice to aggravate cancer progression. In a mouse model of CLL, production of secretory IgM led to more MDSCs, fewer T cells, and shorter survival times for the mice. Thus, secretory IgM may aggravate the progression of this cancer. Cancer Immunol Res; 6(6); 696–710. ©2018 AACR.
RBM20 Mutations Induce an Arrhythmogenic Dilated Cardiomyopathy Related to Disturbed Calcium Handling
Authors: van den Hoogenhof Maarten M.G. , Beqqali Abdelaziz , Amin Ahmad S. , van der Made Ingeborg , Aufiero Simona , Khan Mohsin A.F. , Schumacher Cees A. , Jansweijer Joeri A. , van Spaendonck-Zwarts Karin Y. , Remme Carol Ann , Backs Johannes , Verkerk Arie O. , Baartscheer Antonius , Pinto Yigal M. , Creemers Esther E. 
Published: April 2018

Background:
Mutations in RBM20 (RNA-binding motif protein 20) cause a clinically aggressive form of dilated cardiomyopathy, with an increased risk of malignant ventricular arrhythmias. RBM20 is a splicing factor that targets multiple pivotal cardiac genes, such as Titin (TTN) and CAMK2D (calcium/calmodulin-dependent kinase II delta). Aberrant TTN splicing is thought to be the main determinant of RBM20-induced dilated cardiomyopathy, but is not likely to explain the increased risk of arrhythmias. Here, we investigated the extent to which RBM20 mutation carriers have an increased risk of arrhythmias and explore the underlying molecular mechanism.

Methods:

We compared clinical characteristics of RBM20 and TTN mutation carriers and used our previously generated Rbm20 knockout (KO) mice to investigate downstream effects of Rbm20-dependent splicing. Cellular electrophysiology and Ca
2+
measurements were performed on isolated cardiomyocytes from Rbm20 KO mice to determine the intracellular consequences of reduced Rbm20 levels.

Results:

Sustained ventricular arrhythmias were more frequent in human RBM20 mutation carriers than in TTN mutation carriers (44% versus 5%, respectively,
P
=0.006). Splicing events that affected Ca
2+
- and ion-handling genes were enriched in Rbm20 KO mice, most notably in the genes CamkIIδ and RyR2. Aberrant splicing of CamkIIδ in Rbm20 KO mice resulted in a remarkable shift of CamkIIδ toward the δ-A isoform that is known to activate the L-type Ca
2+
current (
I
Ca,L
). In line with this, we found an increased
I
Ca,L
, intracellular Ca
2+
overload and increased sarcoplasmic reticulum Ca
2+
content in Rbm20 KO myocytes. In addition, not only complete loss of Rbm20, but also heterozygous loss of Rbm20 increased spontaneous sarcoplasmic reticulum Ca
2+
releases, which could be attenuated by treatment with the
I
Ca,L
antagonist verapamil.

Conclusions:

We show that loss of Rbm20 disturbs Ca
2+
handling and leads to more proarrhythmic Ca
2+
releases from the sarcoplasmic reticulum. Patients that carry a pathogenic RBM20 mutation have more ventricular arrhythmias despite a similar left ventricular function, in comparison with patients with a TTN mutation. Our experimental data suggest that RBM20 mutation carriers may benefit from treatment with an
I
Ca,L
blocker to reduce their arrhythmia burden.
Human Neural Stem Cell Extracellular Vesicles Improve Recovery in a Porcine Model of Ischemic Stroke
Authors: Webb Robin L. , Kaiser Erin E. , Jurgielewicz Brian J. , Spellicy Samantha , Scoville Shelley L. , Thompson Tyler A. , Swetenburg Raymond L. , Hess David C. , West Franklin D. , Stice Steven L. 
Published: April 2018

Background and Purpose—
Recent work from our group suggests that human neural stem cell–derived extracellular vesicle (NSC EV) treatment improves both tissue and sensorimotor function in a preclinical thromboembolic mouse model of stroke. In this study, NSC EVs were evaluated in a pig ischemic stroke model, where clinically relevant end points were used to assess recovery in a more translational large animal model.

Methods—
Ischemic stroke was induced by permanent middle cerebral artery occlusion (MCAO), and either NSC EV or PBS treatment was administered intravenously at 2, 14, and 24 hours post-MCAO. NSC EV effects on tissue level recovery were evaluated via magnetic resonance imaging at 1 and 84 days post-MCAO. Effects on functional recovery were also assessed through longitudinal behavior and gait analysis testing.

Results—
NSC EV treatment was neuroprotective and led to significant improvements at the tissue and functional levels in stroked pigs. NSC EV treatment eliminated intracranial hemorrhage in ischemic lesions in NSC EV pigs (0 of 7) versus control pigs (7 of 8). NSC EV–treated pigs exhibited a significant decrease in cerebral lesion volume and decreased brain swelling relative to control pigs 1-day post-MCAO. NSC EVs significantly reduced edema in treated pigs relative to control pigs, as assessed by improved diffusivity through apparent diffusion coefficient maps. NSC EVs preserved white matter integrity with increased corpus callosum fractional anisotropy values 84 days post-MCAO. Behavior and mobility improvements paralleled structural changes as NSC EV–treated pigs exhibited improved outcomes, including increased exploratory behavior and faster restoration of spatiotemporal gait parameters.

Conclusions—
This study demonstrated for the first time that in a large animal model novel NSC EVs significantly improved neural tissue preservation and functional levels post-MCAO, suggesting NSC EVs may be a paradigm changing stroke therapeutic.
Costs and benefits of post-weaning associations in mountain goats
Authors: Charest Castro Karina , Leblond Mathieu , Côté Steeve D. 
Published: April 2018

AbstractTo better understand the potential costs and benefits of prolonged parental care in gregarious species, we studied post-weaning associations in a marked population of mountain goats (Oreamnos americanus) monitored for 22 years. We calculated the occurrence and frequency of associations involving 1- and 2-year-old juveniles. We investigated (1) the influence of maternal characteristics and population size on the formation of post-weaning associations, (2) the short-term costs of associations on maternal reproductive success, and (3) the short-term benefits of associations on life-history traits of juveniles. We found that barren mothers associated more frequently with 1-year-olds than summer yeld and lactating mothers. Associations with 2-year-olds tended to increase the probability that a mother would be barren the following year. Post-weaning associations did not influence the body mass of newborn kids nor the body mass and survival of juveniles. We discuss how benefits for associated juveniles may appear later in life.
Mucron morphology in male entomopathogenic nematodes of the Steinernematidae (Nematoda)
Authors: Mráček Zdeněk , Nermuť Jiří , Půža Vladimír 
Published: April 2018

Summary
The mucron in male steinernematid nematodes may be missing or present either in the first or second generation, or missing in both generations, with variable shape. However, for many species, the information on mucron morphology is incomplete and its taxonomic significance and distribution remain unclear. The present study assessed mucron morphology in males of 26 species using LM and SEM microscopy. For other species we summarised the published data. Furthermore, ancestral character state reconstruction analysis was performed to assess the distribution of mucron morphology within steinernematid phylogeny. In most species, papilla/spine-like or filamentous mucrons occur at least in the second generation. The species gathered in single phylogenetic groups have a similar mucron morphology. Generally, species with a prominent filamentous mucron belong to the ‘kraussei/feltiae’ and ‘carpocapsae’ groups, whereas mostly non-mucronated species occur in ‘glaseri’ and ‘riobrave’ groups. For future descriptions a precise mucron characterisation in both generations of the male is recommended.
A new species of Sporobolus (Poaceae, Chloridoideae) from Trindade Island, Brazil, with comments on the distribution of the genus in the South Atlantic
Authors: Longhi-Wagner Hilda Maria , Alves Ruy José Válka , Silva Nílber Gonçalves da , Guimarães Alessandra Ribeiro 
Published: April 2018

Sporobolus nesiotioides (Poaceae) is described as a new species from Trindade Island, Brazil, using morphological and anatomical characters. The species has affinity with the extinct S. durus from Ascension Island. The presence of the genus on other tropical oceanic islands of the South Atlantic is discussed. Sporobolus nesiotioides (Poaceae) é descrita como nova espécie da Ilha da Trindade, Brasil, usando caracteres morfológicos e anatômicos. Esta espécie tem afinidade com o extinto S. durus, da Ilha de Ascenção. A presença do gênero em outras ilhas oceânicas do Atlântico Sul é discutida.
Muscular and Vascular Issues Induced by Prolonged Standing With Different Work–Rest Cycles With Active or Passive Breaks
Authors: Garcia Maria-Gabriela , Läubli Thomas , Martin Bernard J. 
Published: April 2018

Objective: The aim of this study was to evaluate the long-lasting motor, behavioral, physiological, and perceptual effects of prolonged standing work in three work–rest cycle conditions including passive or active rest breaks. Background: Muscle fatigue has been evidenced after prolonged standing work through physiological and neuromotor measures. It has been postulated that muscle fatigue induced by prolonged work could be attenuated by appropriate scheduling of work and rest periods. However, investigations in this domain remain limited. Method: Thirty participants simulated standing work for 5 hr with work–rest cycles of short, medium, or long standing periods including passive or active breaks. Lower-leg muscle twitch force (MTF), muscle oxygenation, lower-leg volume, postural stability, force control, and discomfort perception were quantified on 2 days. Results: Prolonged standing induced significant changes in all measures immediately after 5 hr of work, indicating a detrimental effect in long-lasting muscle fatigue, performance, discomfort, and vascular aspects. Differences in the measures were not significant between work cycles and/or break type. Conclusion: Similar physiological and motor alterations were induced by prolonged standing. The absence of difference in the effects induced by the tested work–rest cycles suggests that simply altering the work–rest cycle may not be sufficient to counteract the effects of mainly static standing work. Finally, standing for 3 hr or more shows clear detrimental effects. Application: Prolonged standing is likely to contribute to musculoskeletal and vascular symptoms. A limitation to less than 3 hr of mostly static standing in occupational activities could avoid alterations leading to these symptoms.
Comparison of methods to estimate haemodialysis urea clearance
Authors: Mohamed Ahmed , Davenport Andrew 
Published: April 2018

Introduction: Dialysis adequacy is traditionally measured by monthly blood urea sampling and calculating sessional Kt/Vurea. Modern dialysis machines can estimate clearances each session, so we wished to compare online measurements with standard Kt/Vurea. Methods: Urea clearance was estimated by intermittent changes in effective ionic dialysance and by continuous ultraviolet light absorption spent during the mid-week dialysis session. Total body water was calculated by the Watson equation and measured by multifrequency bioimpedance. Results: We compared Kt/Vurea measurements in 162 patients with online assessments: 38 by ultraviolet absorption and 124 by effective ionic dialysance (50 Fresenius 4008 and 74 Fresenius 5008). All online measurements overestimated single-pool Kt/Vurea (ultraviolet absorption mean bias 0.25 ± 0.24, effective ionic dialysance 4008H 0.25 ± 0.21 and 5008H 0.20 ± 0.25; p < 0.001). However, there was no difference between dual-pool Kt/V and ultraviolet absorbance (1.28 ± 0.26 vs 1.29 ± 0.27) or by effective ionic dialysance with the 4008 (1.40 ± 0.26 vs 1.46 ± 0.33), although the effective ionic dialysance 5008 overestimated clearance (1.39 ± 0.27 vs 1.31 ± 0.22; p < 0.01). Similarly, with dual-pool Kt/Vurea, the mean bias for ultraviolet absorption was 0.08 ± 0.35, for effective ionic dialysance (EID) 4008 was 0.13 ± 0.55 and for EID 5008 was −0.2 ± 0.36. Hence, the mean bias was greater with the EID 5008 compared to ultraviolet absorption (0.08 ± 0.35 vs −0.2 ± 0.36 vs p < 0.01). Conclusions: Online measurements allow dialysis adequacy to be measured every session. We found that although online clearances overestimated single-pool Kt/Vurea measurements, there were no significant differences between the continuous ultraviolet light absorbance method and intermittent effective ionic dialysance.
Initiative for Burnout of ICU Caregivers: Feasibility and Preliminary Results of a Psychological Support
Authors: Ricou Bara , Gigon Fabienne , Durand-Steiner Edith , Liesenberg Maud , Chemin-Renais Christine , Merlani Paolo , Delaloye Sylvette 
Published: April 2018

Background: Intensive care unit (ICU) caregivers are at high risk of burnout and the shortage of this highly specialized personal is a problem. The feasibility and impact of a psychological intervention were never assessed in this special context. Methods: A randomized controlled single-blind study in an ICU. The first intervention consisted in weekly problem-based sessions led by psychologists with small groups of caregivers using a systemic approach over 3 months. The modified intervention was lead for 9 months. The scores of Maslach Burnout Inventory and Hospital Anxiety and Depression Scale were compared between the intervention and control groups, before and after the intervention. Results: One-hundred and sixty six caregivers were randomized in intervention and control groups. The major finding was the way the psychologists could modify the original methodology in order to enable caregivers to attend the sessions. Burnout scores tended to decrease across the whole ICU team after the intervention period, more in the intervention group. Participation in the study was poor at 6 months after intervention. Conclusions: This is the first study attempting to evaluate a psychological intervention on the mental health of ICU caregivers. It shows a modified method of a psychological support with a systemic approach in the special environment of ICU. Notwithstanding the modest results related to the short length of the process and the turnover of the personal, we demonstrated that such an approach is feasible. Further studies on larger scale and of longer duration are needed to investigate the effect of such interventions on the mental health of ICU caregivers.
Tunnelling a midline catheter: When the traffic light shifts from yellow to green
Authors: Fabiani Adam , Dreas Lorella , Sanson Gianfranco 
Published: April 2018

Introduction: A safe, largely used practice for difficult venous access patients is positioning a catheter in deeper veins under ultrasound guide. However, the risk of complications is increased when there is a high catheter-to-vein ratio or when the insertion site is in a zone with particular anatomical/physiological characteristics. Case description: A 60-year-old woman admitted to a post-operative intensive care unit after cardiac surgery had a complicated post-operative course. After the removal of a central venous catheter, it was necessary to insert a midline catheter. A complete ultrasound evaluation showed that only the axillary vein was suitable for direct cannulation. To avoid creating an exit site in the axillary cavity, the decision was made to tunnel the catheter to locate an exit site in a safer position. A guidewire was introduced through a needle in the axillary vein. A tunnel was created using a subcutaneous injection of lidocaine. A 14 G/13.3 cm peripheral venous catheter was inserted in the subcutaneous tract. A 4 Fr/20 cm catheter was introduced through the peripheral venous catheter and moved to the axillary vein through the previously inserted sheath. No acute complications occurred. The catheter was accessed several times a day during the period following its insertion to infuse drugs and take blood samples. It was removed 50 days after its placement because it was no longer needed. No symptomatic thrombosis or infections occurred. Conclusion: The placement of the tunnelled midline catheter is shown to be a safe and effective way to ensure vascular access for almost 2 months.
The Morbidity and Mortality of Laparoscopic Appendectomy in Patients with Cirrhosis
Authors: Al-Azzawi Yasir , Al-Abboodi Yasir , Fasullo Matthew , Najuib Tarek 
Published: April 2018

Introduction: The perioperative mortality is significantly higher in patients with cirrhosis undergoing certain surgical procedures. In this study, we examined the inpatient perioperative mortality and morbidities in cirrhotic people who underwent laparoscopic appendectomy. Methods: We performed a retrospective analysis using the National Inpatient Sample database for 2010. Inclusion criteria were all race and sex who are 18 years or older. Those who have laparoscopic appendectomy and have a history of liver cirrhosis were assigned to case group. An equal random number of appendectomy-related admissions and those who have no history of liver cirrhosis were selected and placed in the control group. A binary logistic regression statistical test was used to examine the odds ratio for the mortality difference and postoperative complication including pneumonia, urinary tract infection (UTI), surgical site infection, postoperative bleeding. IBM SPSS statistics was used to execute the analysis. A confidence interval of 95% and P value less than .05 were determined to define the statistical significance. Result: A total of 754 appendectomy-related admissions were identified—376 appendectomy-related admissions and history of cirrhosis and 378 admissions with appendectomy and no history of cirrhosis. Control group was not found to be statistically different from the case group when it comes to age, race, and sex. Of 754, 520 were white (73.5%), 334 (44.3%) were men. The mean age was 43.75 years for the case group and 46.68 years for the control group. Comparing cirrhotic with noncirrhotic group, the mean length of stay was 1.1 vs 1.52 days, inpatient mortality was 2 (0.5%) vs 1 (0.3%) ( P = .56), pneumonia 8 (2.1%) vs 3 (0.8%) ( P = .142), surgical site infection 3 (0.8%) vs 2 (0.5%) ( P = .652), UTI 18 (4.8%) vs 12 (3.2%) ( P = .26), and postoperative bleeding 3 (0.8%) vs 2 (0.5%) ( P = .65). Conclusions: Appendectomy-related morbidity and mortality in cirrhotic patients are not different from noncirrhotic patients.