bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical progression at initiation of a life-extending therapy (LET) in metastatic castration-resistant prostate cancer (mCRPC) is associated with a poor prognosis, whatever the treatment-line: Results of the CATS retrospective registry.
Authors: Delanoy Nicolas , Hardy-Bessard Anne-Claire , Le Moulec Sylvestre , Basso Umberto , Birtle Alison Jane , Thomson Alastair H , Krainer Michael , De Giorgi Ugo , Hasbini Ali , Daugaard Kirsten Gedske , Bahl Amit , Chowdhury Simon , Caffo Orazio , Beuzeboc Philippe , Spaeth Dominique , Eymard Jean-Christophe , Flechon Aude , Thiery-Vuillemin Antoine , Efstathiou Eleni , Oudard Stephane 
Published: March 2020

189 Background: We previously reported that cancer pain was associated with a poor prognosis in mCRPC patients (pts) treated with docetaxel (D) ( Oudard, BJU Int 2009). Asymptomatic chemo-naive pts treated with novel androgen receptor targeted agent (H) have a greater overall survival (OS) than those with mild symptoms ( Miller, Eur Urol 2018). We thus investigated the impact on OS of progression type at initiation of first-, second- and third-line of LET in a large cohort of mCRPC pts (CATS registry) treated with D, cabazitaxel (C) and H. Methods: 669 consecutive mCRPC pts treated with 3 LETs (DCH, n= 158; DHC, n=456; HDC, n=55) were retrospectively reviewed. Type of progression: PSA alone, radiographic ± PSA, clinical ± PSA ± radiographic at initiation of each LET was evaluable in 661 pts. Clinical progression was defined by worsening of cancer-related pain or symptoms as per physician judgment. Results: Clinical progression at initiation of LET increased with the number of treatment lines and was consistently associated with a worse outcome. Clinical progression was associated with a significantly shorter duration of treatment with H but had no influence on duration of taxanes. Conclusions: In pts treated with 3 LTEs (D, C and H) clinical progression at sequence initiation is associated with a poor OS and a shorter duration of hormonal treatment. These data may help guide treatment decisions.[Table: see text]
Neurogenesis in the inner ear: the zebrafish statoacoustic ganglion provides new neurons from a Neurod/Nestin-positive progenitor pool well into adulthood
Authors: Schwarzer Simone , Asokan Nandini , Bludau Oliver , Chae Jeongeun , Kuscha Veronika , Kaslin Jan , Hans Stefan 
Published: March 2020

ABSTRACT
The vertebrate inner ear employs sensory hair cells and neurons to mediate hearing and balance. In mammals, damaged hair cells and neurons are not regenerated. In contrast, hair cells in the inner ear of zebrafish are produced throughout life and regenerate after trauma. However, it is unknown whether new sensory neurons are also formed in the adult zebrafish statoacoustic ganglion (SAG), the sensory ganglion connecting the inner ear to the brain. Using transgenic lines and marker analysis, we identify distinct cell populations and anatomical landmarks in the juvenile and adult SAG. In particular, we analyze a Neurod/Nestin-positive progenitor pool that produces large amounts of new neurons at juvenile stages, which transitions to a quiescent state in the adult SAG. Moreover, BrdU pulse chase experiments reveal the existence of a proliferative but otherwise marker-negative cell population that replenishes the Neurod/Nestin-positive progenitor pool at adult stages. Taken together, our study represents the first comprehensive characterization of the adult zebrafish SAG showing that zebrafish, in sharp contrast to mammals, display continued neurogenesis in the SAG well beyond embryonic and larval stages.
The startle reflex in echolocating odontocetes: basic physiology and practical implications
Authors: Götz Thomas , Pacini Aude F. , Nachtigall Paul E. , Janik Vincent M. 
Published: March 2020

ABSTRACT
The acoustic startle reflex is an oligo-synaptic reflex arc elicited by rapid-onset sounds. Odontocetes evolved a range of specific auditory adaptations to aquatic hearing and echolocation, e.g. the ability to downregulate their auditory sensitivity when emitting clicks. However, it remains unclear whether these adaptations also led to changes of the startle reflex. We investigated reactions to startling sounds in two bottlenose dolphins (Tursiops truncatus) and one false killer whale (Pseudorca crassidens). Animals were exposed to 50 ms, 1/3 octave band noise pulses of varying levels at frequencies of 1, 10, 25 and 32 kHz while positioned in a hoop station. Startle responses were quantified by measuring rapid muscle contractions using a three-dimensional accelerometer attached to the dolphin. Startle magnitude increased exponentially with increasing received levels. Startle thresholds were frequency dependent and ranged from 131 dB at 32 kHz to 153 dB at 1 kHz (re. 1 µPa). Startle thresholds only exceeded masked auditory AEP thresholds of the animals by 47 dB but were ∼82 dB above published behavioural audiograms for these species. We also tested the effect of stimulus rise time on startle magnitude using a broadband noise pulse. Startle responses decreased with increasing rise times from 2 to 100 ms. Models suggested that rise times of 141–220 ms were necessary to completely mitigate startle responses. Our data showed that the startle reflex is conserved in odontocetes and follows similar principles as in terrestrial mammals. These principles should be considered when assessing and mitigating the effects of anthropogenic noise on marine mammals.
Correlation between salivary estrogen levels and oral epithelial cytokeratin 5 expression
Authors: Handajani Juni , Effendi Nuraini , Sosroseno Wihaskoro 
Published: March 2020

Background: Estrogen expression levels may be associated with age and may affect keratinization of the hard palate. Keratinized epithelium expresses cytokeratin 5 and 14 in the basal layer. The aim of this study was to determine the correlation between the levels of salivary estrogen and number of cytokeratin 5-positive oral epithelial cells. Methods: A total of 30 female subjects were recruited and divided into children, adults and elderly (N=10 per group). Salivary estrogen levels and cytokeratin 5-expressing oral epithelial cells were assessed using ELISA and immunohistological methods, respectively. Data were analyzed using ANOVA with post hoc LSD test and Pearson’s correlation coefficient. Results: The results showed that both the number of cytokeratin 5-positive cells and the level of salivary estrogen were significantly higher in adults but decreased in the elderly, as compared with those in children (p<0.05). Furthermore, the levels of salivary estrogen were significantly correlated with the number of cytokeratin 5-positive cells (r=0.815). The ANOVA result showed significance difference cytokeratin 5 expression and estrogen level (p<0.05). The post hoc LSD test revealed cytokeratin 5 expression and estrogen level to be significantly different in children, adults, and elderly participants (p<0.05). Conclusions: These results suggest that the profile of salivary estrogen and oral epithelial cell-expressed cytokeratin 5 may be positively correlated with age and depend on age.
Views on social media and its linkage to longitudinal data from two generations of a UK cohort study
Authors: Di Cara Nina H. , Boyd Andy , Tanner Alastair R. , Al Baghal Tarek , Calderwood Lisa , Sloan Luke S. , Davis Oliver S. P. , Haworth Claire M. A. 
Published: March 2020

Background: Cohort studies gather huge volumes of information about a range of phenotypes but new sources of information such as social media data are yet to be integrated. Participant’s long-term engagement with cohort studies, as well as the potential for their social media data to be linked to other longitudinal data, could provide novel advances but may also give participants a unique perspective on the acceptability of this growing research area. Methods: Two focus groups explored participant views towards the acceptability and best practice for the collection of social media data for research purposes. Participants were drawn from the Avon Longitudinal Study of Parents and Children cohort; individuals from the index cohort of young people (N=9) and from the parent generation (N=5) took part in two separate 90-minute focus groups. The discussions were audio recorded and subjected to qualitative analysis. Results: Participants were generally supportive of the collection of social media data to facilitate health and social research. They felt that their trust in the cohort study would encourage them to do so. Concern was expressed about the collection of data from friends or connections who had not consented. In terms of best practice for collecting the data, participants generally preferred the use of anonymous data derived from social media to be shared with researchers. Conclusion: Cohort studies have trusting relationships with their participants; for this relationship to extend to linking their social media data with longitudinal information, procedural safeguards are needed. Participants understand the goals and potential of research integrating social media data into cohort studies, but further research is required on the acquisition of their friend’s data. The views gathered from participants provide important guidance for future work seeking to integrate social media in cohort studies.
On the Role of Group Size in Tournaments: Theory and Evidence from Laboratory and Field Experiments
Authors: List John A. , van Soest Daan , Stoop Jan , Zhou Haiwen 
Published: March 2020

We explore how individual equilibrium effort in tournaments varies with the number of contestants. The probability of winning a tournament depends on both effort and luck, and we show that the distribution of the luck component is critical in determining individual equilibrium effort. Our theory predicts that equilibrium effort is an increasing (decreasing) function of the number of contestants if there is considerable (little) mass on favorable draws. We test our theory using both laboratory and field experiments, and find substantial support for our theory in both settings. This paper was accepted by Teck Ho, behavioral economics.
Comparison between 4 weeks passive static stretching and proprioceptive neuromuscular facilitation programmes on neuromuscular properties of hamstring muscles: a randomised clinical trial
Authors: Cini Anelize , de Vasconcelos Gabriela Souza , Soligo Milena Caumo , Felappi Cassiele , Rodrigues Rodrigo , Aurélio Vaz Marco , Lima Cláudia Silveira 
Published: March 2020

Background/aims Studies have shown the efficacy of stretching to increase the hip flexion range of motion but studies regarding its effects are not unanimous about the most efficient technique. The aim of this study was to compare the effect of two stretching techniques on the neuromuscular properties of the hamstring muscles. Methods A total of 18 women (aged 24 ± 2.52 years old) participated, and were divided into three groups: a control group, a passive static stretching group and a propioceptive neuromuscular facilitation stretching group. Evaluations of variables of the hamstring muscles were performed before and after the training period. The intervention was carried out for 30 seconds, three times a week for a total of 4 weeks. Results A significant difference was found in the range of motion in the passive static stretching group (pre=80.8° [±11.0] and post=94.5° [±10.2]; t(5)=−3.755; P=0.013) and in concentric torque (passive static stretching group – pre=66.3 Nm [±12.9] and post=70.0 Nm [±8.1]; t(5)=−1.267; P=0.023; propioceptive neuromuscular facilitation stretching group – pre=79.1 Nm [±12.7] and post=83.5 Nm [±11.6]; t(5)=−1.917; P=0.014; control group – pre=71.1 Nm [±10.1] and post=74.1 Nm [±14.6]; t(5)=−1.275; P=0.003). Conclusions Passive static stretching was superior to propioceptive neuromuscular facilitation when comparing the increase range of motion in hip flexion, even without neural and structural changes in hamstring muscles after a 4-week period.
Epigenetic Alterations Are Associated With Gastric Emptying Disturbances in Diabetes Mellitus
Authors: Puthanmadhom Narayanan Susrutha , Lee Jeong-Heon , Bhagwate Aditya , Kuwelker Saatchi , Yan Huihuang , Ordog Tamas , Bharucha Adil E. 
Published: March 2020

INTRODUCTION:
Epigenetic modifications have been implicated to mediate several complications of diabetes mellitus (DM), especially nephropathy and retinopathy. Our aim was to ascertain whether epigenetic alterations in whole blood discriminate among patients with DM with normal, delayed, and rapid gastric emptying (GE).

METHODS:
Using the ChIP-seq (chromatin immunoprecipitation combined with next-generation sequencing) assays, we compared the genome-wide enrichment of 3 histone modifications (i.e., H3K4me3, H3K9ac, and H3K27ac) in buffy coats from 20 diabetic patients with gastrointestinal symptoms and normal (n = 6), delayed (n = 8), or rapid (n = 6) GE.

RESULTS:
Between patients with DM with delayed vs normal GE, there were 108 and 54 genes that were differentially bound (false discovery rate < 0.05) with H3K27ac and H3K9ac, respectively; 100 genes were differentially bound with H3K9ac in patients with rapid vs normal GE. The differentially bound genes with H3K27ac were functionally linked to the type 2 immune response, particularly Th2 cell activation and function (e.g., CCR3, CRLF2, CXCR4, IL5RA, and IL1RL1) and glucose homeostasis (FBP-1, PDE4A, and CMKLR1). For H3K9ac, the differentially occupied genes were related to T-cell development and function (e.g., ICOS and CCR3) and innate immunity (RELB, CD300LB, and CLEC2D). Compared with normal GE, rapid GE had differential H3K9ac peaks at the promoter site of diverse immunity-related genes (e.g., TNFRSF25 and CXCR4) and genes related to insulin resistance and glucose metabolism. Motif analysis disclosed enrichment of binding sites for transcription factors relevant to the pathogenesis and complications of DM.

DISCUSSION:
GE disturbances in DM are associated with epigenetic alterations that pertain to dysimmunity, glucose metabolism, and other complications of DM.
Increased Th17-Related Cytokine Serum Levels in Patients With Multiple Polyps of Unexplained Origin
Authors: Alustiza Miren , Hernández-Illán Eva , Juárez Miriam , Giner-Calabuig Mar , Mira Cristina , Martínez-Roca Alejandro , Bujanda Luis , Rodríguez-Moranta Francisco , Cubiella Joaquín , de-Castro Luisa , Marín-Gabriel José-Carlos , Herreros-de-Tejada Alberto , Fernández-Bañares Fernando , Nicolás-Pérez David , Giménez Paula , Martínez-Cardona Claudia , Francés Rubén , Murcia Oscar , Jover Rodrigo 
Published: March 2020

OBJECTIVES:
Most patients with multiple colonic polyps do not have a known genetic or hereditary origin. Our aim was to analyze the presence of inflammatory cytokines and levels of glucose, insulin, and C-reactive protein (CRP) in patients with multiple colonic polyps.

METHODS:
Eighty-three patients with 10 or more adenomatous or serrated polyps and 53 control people with normal colonoscopy were included. Smoking habits were registered, and glucose, CRP, and basal insulin in the serum/blood were measured. Quantification of IL-2, IL-4, IL-6, IL-10, IL-11, IL-17A, and IL-23 cytokine levels in the serum was performed by a high-sensitivity enzyme-linked immunosorbent assay.

RESULTS:
Smoking and diabetes were more prevalent in those with colonic polyps than in the control people (67% vs 16%, P = 0.001; 11% vs 2%, P = 0.048). In addition, the cytokine serum levels were higher, i.e., IL-2 (P = 0.001), IL-4 (P = 0.001), IL-6 (P = 0.001), IL-17A (P = 0.001), IL-23 (P = 0.014), and CRP (P = 0.003). Adjusting for sex, smoking, and diabetes in a multivariate analysis, IL-2, IL-4, IL-6, IL-17A, and IL-23 remained independently elevated in cases with multiple polyps.

DISCUSSION:
These results indicate that immune responses mediated by Th17 cells may be involved in the pathogenesis of multiple colonic polyps.
“I pray sir, hear me: I am married”: Language and Sexual Politics in Webster’sThe Duchess of Malfi
Authors: Hamamra Bilal Tawfiq 
Published: March 2020

AbstractThis article follows the critical lines of new historicism, feminism, psychoanalysis and performance studies so as to reveal Webster’s challenge of the conventional gender roles via the binary opposites of speech and silence. Within the context of new historicism, I contend that Webster’sThe Duchess of Malfi(1613–1614) comments on the corruption and abuse of absolute political power within the reign of King James I and the Catholic Church through the figures of Ferdinand (the head of the state) and the Cardinal (the head of the Church). Contrary to the new historicism’s conception of all-encompassing ideology, Webster attributes male figures’ loss of control over their voices and the movement of the plot to their aural closure to the Duchess’s moral speech. Following the methodology of feminism, I argue that this tragedy enacts an inversion of gender roles with respect to discourse. Webster associates the Duchess of Malfi’s voice and silence with honesty and dramatic authority and her tyrannical brothers’ voices with incestuous and murderous desires. Drawing on Freudian and Jungian concepts of psychoanalysis, I propose that Ferdinand and the Cardinal whose voices are associated with murderous and incestuous desires are linked with the psychic zone of the id while the Duchess, who expresses and acts on her sexual desire within the sphere of marriage, is linked to the ego, the reality principle. Her appearance as an echo in the tragic closure reveals her progression towards perfection, the superego. While Ferdinand’s misogyny is a projection of his unconscious sexual desire towards his sister, his madness is a sign of incestuous frustration. At a meta-theatrical level, I argue that this subversion of gender roles via the binary opposites of embodiment and disembodiment and silence and speech is linked to theatrical performance. Webster shows that the boy actor impersonating the Duchess’s voice and silence appropriates masculine agency while male figures’ voices are linked to madness and lack of subjectivity.
Bodily and Spiritual Borders in the Parsi Males of Rohinton Mistry’s Tales from Firozsha Baag
Authors: Somacarrera-Íñigo Pilar 
Published: March 2020

Abstract
In this essay, I am going to read the bodies of the Parsi male characters in Rohinton Mistry’s Tales from Firozsha Baag (1987) through the lens of Julia Kristeva’s theories of the abject. According to Kristeva, the abject refers to the human reaction (horror, vomit) to a threatened breakdown in meaning caused by the loss of the distinction between subject and object or between self and other, a reaction elicited by bodily fluids such as excrement, blood or even semen. The bodies of the Parsi males in Tales of Firozsha Baag are a site of awareness in which the “bodily borders” (Moreno-Álvarez 2014: 39) explode. In the first section of the essay, I will discuss the stories “One Sunday”, “The Collectors” and “Exercisers”. In the second section, I will delve into Mistry’s Canadian trilogy — ”Squatter”, “Lend Me Your Light” and “Swimming Lessons” — whose main subject is the young Parsi male striving for happiness and individual liberation (moksha) through emigration to North America. I will conclude that these Parsi men have difficulties integrating themselves in their Indian and North American contexts because the realms of the corporeal and the spiritual are, quoting Frantz Fanon’s phrase, “zones of occult instability” (Fanon 1967: 21).
Performance comparison of two next-generation sequencing panels to detect actionable mutations in cell-free DNA in cancer patients
Authors: Macías Mónica , Cañada-Higueras Eva , Alegre Estibaliz , Bielsa Arancha , Gracia Javier , Patiño-García Ana , Ferrer-Costa Roser , Sendino Teresa , Andueza María P. , Mateos Beatriz , Rodríguez Javier , Corral Jesús , Gúrpide Alfonso , Lopez-Picazo José M. , Perez-Gracia Jose L. , Gil-Bazo Ignacio , Alkorta-Aranburu Gorka , González Álvaro 
Published: March 2020

Abstract

Background
Genomic alterations studies in cell-free DNA (cfDNA) have increasing clinical use in oncology. Next-generation sequencing (NGS) technology provides the most complete mutational analysis, but nowadays limited data are available related to the comparison of results reported by different platforms. Here we compare two NGS panels for cfDNA: Oncomine™ Pan-Cancer Cell-Free Assay (Thermo Fisher Scientific), suitable for clinical laboratories, and Guardant360® (GuardantHealth), with more genes targeted but only available in an outsourcing laboratory.

Methods
Peripheral blood was obtained from 16 advanced cancer patients in which Guardant360® (G360) was requested as part of their clinical assistance. Blood samples were sent to be analyzed with G360 panel, and an additional blood sample was drawn to obtain and analyze cfDNA with Oncomine™ Pan-Cancer (OM) panel in an Ion GeneStudio S5™ System.

Results
cfDNA analysis globally rendered 101 mutations. Regarding the 55/101 mutations claimed to be included by manufacturers in both panels, 17 mutations were reported only by G360, 10 only by OM and 28 by both. In those coincident cases, there was a high correlation between the variant allele fractions (VAFs) calculated with each panel (r = 0.979, p < 0.01). Regarding the six actionable mutations with an FDA-approved therapy reported by G360, one was missed with OM. Also, 12 mutations with clinical trials available were reported by G360 but not by OM.

Conclusions
In summary, G360 and OM can produce different mutational profile in the same sample, even in genes included in both panels, which is especially important if these mutations are potentially druggable.
A progesterone receptor membrane component 1 antagonist induces large vesicles independent of progesterone receptor membrane component 1 expression
Authors: Wang-Eckhardt Lihua , Eckhardt Matthias 
Published: March 2020

AbstractTreatment of different cell lines with progesterone receptor membrane component 1 (PGRMC1) antagonist AG-205 rapidly induces the formation of large vesicular structures that likely represent endosomes. Crispr/Cas9 was used to target the PGRMC1 and progesterone receptor membrane component 2 (PGRMC2) genes in CHO-K1 and HeLa. Unexpectedly, deficiency in one of these or both genes did not inhibit the formation of enlarged vesicles by AG-205, demonstrating additional molecular target(s) of this compound besides PGRMC1. Thus, AG-205 cannot be regarded as a PGRMC1-specific antagonist. However, provided that its currently unknown target(s) will be identified, AG-205 may serve as a new reagent to study endosomal trafficking.
Organizational challenges in the management of point-of-care diagnostics in healthcare facilities
Authors: Kachler Marco , Maschek Christiane 
Published: March 2020

Abstract
This text is a synopsis of the “Seminar on Organizational Aspects of POCT Management” which was part of the 4th Munich POCT symposium 2019. The session was chaired in part 1 by Christiane Maschek (Berlin) and Anke Urban (Ludwigshafen), and in part 2 by Barbara Oschwald-Häg (Offenburg) and Marco Kachler (Klagenfurt/AT). The seminar was held in German in order to allow non-English-speaking medical technicians the full understanding of the presented contents. Part 1: Nice to Know – Challenges for networking POCT systems (Michaela Markhoff, Hamburg). Best Practice – Implementation of POCT in a hospital without central lab services (Jennifer Planz, Essen). Best Practice – Benefits of the POCT commission demonstrated using the example of implementing glucose POCT devices (Barbara Oschwald-Häg, Offenburg). Part 2: Best Practice – Challenges of a group-wide implementation of a POCT competence management (Sandra Mütze, Berlin). Nice to Know – Learning from mistakes in preanalytics (Reno Konzack, Berlin). New IFCC recommendation for checking reference intervals (Harald Maier, Altötting).