bluuebunny/crossref_metadata_2025 huggingface dataset:
Parental communication on sexual and reproductive health issues and its associated factors among preparatory school students in Debre Tabor, Northcentral Ethiopia: institution based cross-sectional study
Authors: Mekie Maru , Taklual Wubet , Melkie Abenezer , Addisu Dagne
Published: September 2019

Objective

This study was aimed to assess parental communication on sexual and reproductive health (SRH) issues and its associated factors among preparatory school students in Debre Tabor, Northcentral Ethiopia. Institution based cross sectional study was employed among 394 preparatory school students through self-administered questionnaire.

Result

A total of 394 students were participated in the study with a response rate of 100%. The magnitude of parental communication on SRH issues was found to be 68.5%, (95% CI (63.7, 72.8)). Low grade (AOR = 0.31, 95% CI (0.17, 0.58)), feel embraced to discuss about SRH issues (AOR = 0.31, 95% CI (0.17, 0.56)), and living with mother/father (AOR = 0.15, 95% CI (0.06, 0.36)) were associated with reduced parental communication on SRH. While, family size < 5 (AOR = 2.46, 95% CI (1.25, 4.84)), and believe on the importance of discussion on SRH (AOR = 10.83, 95% CI (5.07, 23.17) were found to be associated with increased communication about SRH issues. Health education shall be given to preparatory school students on importance of discussion on SRH issues and related consequences of risky sexual behaviors.
Ontology based mining of pathogen–disease associations from literature
Authors: Kafkas Şenay , Hoehndorf Robert
Published: September 2019

Background

Infectious diseases claim millions of lives especially in the developing countries each year. Identification of causative pathogens accurately and rapidly plays a key role in the success of treatment. To support infectious disease research and mechanisms of infection, there is a need for an open resource on pathogen–disease associations that can be utilized in computational studies. A large number of pathogen–disease associations is available from the literature in unstructured form and we need automated methods to extract the data.

Results

We developed a text mining system designed for extracting pathogen–disease relations from literature. Our approach utilizes background knowledge from an ontology and statistical methods for extracting associations between pathogens and diseases. In total, we extracted a total of 3420 pathogen–disease associations from literature. We integrated our literature-derived associations into a database which links pathogens to their phenotypes for supporting infectious disease research.

Conclusions

To the best of our knowledge, we present the first study focusing on extracting pathogen–disease associations from publications. We believe the text mined data can be utilized as a valuable resource for infectious disease research. All the data is publicly available from https://github.com/bio-ontology-research-group/padimi
and through a public SPARQL endpoint from http://patho.phenomebrowser.net/.
Assessing exhibition swine as potential disseminators of infectious disease through the detection of five respiratory pathogens at agricultural exhibitions
Authors: Lauterbach Sarah E. , Nelson Sarah W. , Robinson Meghann E. , Lorbach Josh N. , Nolting Jacqueline M. , Bowman Andrew S.
Published: September 2019

Widespread geographic movement and extensive comingling of exhibition swine facilitates the spread and transmission of infectious pathogens. Nasal samples were collected from 2862 pigs at 102 exhibitions and tested for five pathogens. At least one pathogen was molecularly detected in pigs at 63 (61.8%) exhibitions. Influenza A virus was most prevalent and was detected in 498 (17.4%) samples. Influenza D virus was detected in two (0.07%) samples. More than one pathogen was detected in 165 (5.8%) samples. Influenza A virus remains a top threat to animal and human health, but other pathogens may be disseminated through the exhibition swine population.
The potential of acetylsalicylic acid and vitamin E in modulating inflammatory cascades in chickens under lipopolysaccharide-induced inflammation
Authors: Konieczka Paweł , Barszcz Marcin , Kowalczyk Paweł , Szlis Michał , Jankowski Jan
Published: September 2019

Distinct enzymes, including cyclooxygenase 1 and 2 (COX-1 and COX-2), lipoxygenase (LOXs), and cytochrome P450 monooxygenase (CYP450), produce different stress mediators and mediate inflammation in birds. Bioactive agents such as acetylsalicylic acid (ASA) and vitamin E (vE) may affect enzyme activities and could be used in poultry production to control the magnitude of acute phase inflammation. Here, we characterized COX, LOX, and CYP450 mRNA expression levels in chicken immune tissues in response to Escherichia coli lipopolysaccharide (LPS) challenge and investigated whether ASA and vE could alter gene expression. Additionally, for the first time in chickens, we evaluated oxygen consumption by platelet mitochondria as a biomarker of mitochondria function in response to ASA- and vE. LPS challenge compromised bird growth rates, but neither dietary ASA nor vE significantly ameliorated this effect; however, gradually increasing dietary vE levels were more effective than basal levels. ASA regulated arachidonic acid metabolism, providing an eicosanoid synthesis substrate, whereas gradually increasing vE levels evoked aspirin resistance during challenge. Gene expression in immune tissues was highly variable, indicating a complex regulatory network controlling inflammatory pathways. However, unlike COX-1, COX-2 and CYP450 exhibited increased mRNA expression in some cases, suggesting an initiation of novel anti-inflammatory and pro-resolving signals during challenge. Measuring oxygen consumption rate, we revealed that neither the ASA nor vE levels applied here exerted toxic effects on platelet mitochondria.
Codebook-based precoding for generalized spatial modulation with diversity
Authors: Sourour Essam
Published: September 2019

This paper investigates codebook-based precoding for spatial modulation (SM) and generalized spatial modulation (GSM) systems. Codebook-based precoding allows the system to dispense with full channel state information at the transmitter (CSIT). This considerably reduces the feedback overhead. Phase-only codebooks with systematic structure are investigated since they avoid increasing the peak to average power ratio of the transmitted signal. It is shown that the proposed phase-only codebooks yield equivalent performance to published codebooks that involve gain and phase. In addition, a gain-only codebook is designed to supplement the phase-only codebook and reduce the bit error rate (BER) further. We also compare the performance with the Grassmannian codebooks which are proposed for other multiple-in-multiple-out (MIMO) systems. In GSM systems, several antennas are simultaneously active as a transmit antenna combination (TAC). The BER performance of unprecoded GSM systems is typically inferior to SM systems due to correlation among TACs. However, with codebook precoding, this effect is mitigated, and the performance of the GSM system becomes superior to the SM system. We investigate codebook precoding for GSM systems where precoding is performed per-TAC or per-antenna. Moreover, we investigate the GSM system where the TACs are selected adaptively based on the achievable benefit from codebook precoding. Using computer simulation, it is shown that the performance of the proposed codebooks is very promising in both SM and GSM systems. Per-antenna precoding is superior to per-TAC precoding. Adaptive TACs selection further improves performance.
An alternating iteration algorithm for solving the split equality fixed point problem with L-Lipschitz and quasi-pseudo-contractive mappings
Authors: Li Meixia , Zhou Xueling , Che Haitao
Published: September 2019

In this paper, we are concerned with the split equality common fixed point problem. It is a significant generalization of the split feasibility problem, which can be used in various disciplines, such as medicine, military and biology, etc. We propose an alternating iteration algorithm for solving the split equality common fixed point problem with L-Lipschitz and quasi-pseudo-contractive mappings and prove that the sequence generated by the algorithm converges weakly to the solution of this problem. Finally, some numerical results are shown to confirm the feasibility and efficiency of the proposed algorithm.
Non-linear population discrete models with two time scales: re-scaling of part of the slow process
Authors: Sanz Luis , Bravo de la Parra Rafael , Marvá Marcos , Sánchez Eva
Published: September 2019

In this work we present a reduction result for discrete-time systems with two time scales. In order to be valid, previous results in the field require some strong hypotheses that are difficult to check in practical applications. Roughly speaking, the iterates of a map as well as their differentials must converge uniformly on compact sets. Here, we eliminate the hypothesis of uniform convergence of the differentials at no significant cost in the conclusions of the result. This new result is then used to extend to non-linear cases the reduction of some population discrete models involving processes acting at different time scales. In practical cases, some processes that occur at a fast time scale are often only measured at slow time intervals, notably mortality. For a general class of linear models that include such a kind of processes, it has been shown that a more realistic approach requires the re-scaling of those processes to be considered at the fast time scale. We develop the same type of re-scaling in some non-linear models and prove the corresponding reduction results. We also provide an application to a particular model of a structured population in a two-patch environment.
Predator–prey pattern formation driven by population diffusion based on Moore neighborhood structure
Authors: Huang Tousheng , Zhang Huayong , Hu Zhengran , Pan Ge , Ma Shengnan , Zhang Xiumin , Gao Zichun
Published: September 2019

Diffusion-driven instability is a basic nonlinear mechanism for pattern formation. Therefore, the way of population diffusion may play a determinative role in the spatiotemporal dynamics of biological systems. In this research, we launch an investigation on the pattern formation of a discrete predator–prey system where the population diffusion is based on the Moore neighborhood structure instead of the von Neumann neighborhood structure widely applied previously. Under pattern formation conditions which are determined by Turing instability analysis, numerical simulations are performed to reveal the spatiotemporal complexity of the system. A pure Turing instability can induce the self-organization of many basic types of patterns as described in the literature, as well as new spiral-spot and labyrinth patterns which show the temporally oscillating and chaotic property. Neimark–Sacker–Turing and flip–Turing instability can lead to the formation of circle, spiral and much more complex patterns, which are self-organized via spatial symmetry breaking on the states that are homogeneous in space and non-periodic in time. Especially, the emergence of spiral pattern suggests that spatial order can generate from temporal disorder, implying that even when the predator–prey dynamics in one site is chaotic, the spatially global dynamics may still be predictable. The results obtained in this research suggest that when the way of population diffusion changes, the pattern formation in the predator–prey systems demonstrates great differences. This may provide realistic significance to explain more general predator–prey coexistence.
3D effects of a bone-anchored intra-oral protraction in treating class III growing patient: a pilot study
Authors: Almuzian Mohammed , Almukhtar Anas , Ulhaq Aman , Alharbi Fahad , Darendeliler M. Ali
Published: September 2019

Objectives

The aim of this prospective case series study is to assess the three-dimensional (3D) skeletal and soft tissue effects of the alternate rapid maxillary expansion and constriction (Alt-RAMEC) protocol in conjunction with a miniscrew-supported class III elastic wear in class III growing patients.

Materials and methods

Fourteen consecutive participants (mean age 12.05 ± 1.09 years), who displayed class III malocclusions with retrognathic maxillae, were recruited. A cone beam computed tomography (CBCT) scan was acquired before commencing treatment (T1). All participants were treated with a tooth-bone-borne rapid maxillary expansion (hybrid MARME) appliance that was activated by the Alt-RAMEC protocol for 9 weeks. This was followed by full-time class III elastics, delivering 400 g/side, to protract the maxilla. When a positive overjet was achieved, protraction was ceased and a post-treatment CBCT scan (T2) was taken. The 3D analysis of pre- and post-treatment CBCT scans was blinded. The scans were registered on the anterior cranial base. The Euclidean distance between the two extracted surface models of the pre- and post-treatment scans was displayed as a color surface map.

Results

All participants completed the intervention successfully. The majority of the participants showed protraction of the anterior maxillary region (71.4%) and in the zygomatic processes (64.2%). The maxilla significantly protracted (SNA 1.87° ± 1.06°; Vert.T-A 3.29 ± 1.54 mm), while the mandibular base significantly redirected posteriorly (SNB − 2.03° ± 0.85°, Vert.T-B − 3.43 ± 4.47 mm) and that was reflected on the ANB and Wits measurements. No adverse effects were observed.

Conclusion

Class III elastics combined with the Alt-RAMEC activation protocol of the hybrid MARME appliance is an effective treatment method for mild/moderate class III malocclusions. A long-term follow-up and comparisons with other treatment modalities are required.
Independent validation of machine learning in diagnosing breast Cancer on magnetic resonance imaging within a single institution
Authors: Ji Yu , Li Hui , Edwards Alexandra V. , Papaioannou John , Ma Wenjuan , Liu Peifang , Giger Maryellen L.
Published: September 2019

Background

As artificial intelligence methods for the diagnosis of disease advance, we aimed to evaluate machine learning in the predictive task of distinguishing between malignant and benign breast lesions on an independent clinical magnetic resonance imaging (MRI) dataset within a single institution for subsequent use as a computer aid for radiologists.

Methods

Computer analysis was conducted on consecutive dynamic contrast-enhanced MRI (DCE-MRI) studies from 1483 breast cancer and 496 benign patients who underwent MRI examinations between February 2015 and October 2017; with the age ranges of the cancer and benign patients being 19 to 77 and 16 to 76 years old, respectively. Cases were separated into a training dataset (years 2015 & 2016; 1444 cases) and an independent testing dataset (year 2017; 535 cases) based solely on MRI examination date. After radiologist indication of the lesion, the computer automatically segmented and extracted radiomic features, which were subsequently merged with a support-vector machine (SVM) to yield a lesion signature. Area under the receiving operating characteristic (ROC) curve (AUC) with 95% confidence intervals (CI) served as the primary figure of merit in the statistical evaluation for this clinical classification task.

Results

In the task of distinguishing malignant and benign breast lesions DCE-MRI, the trained predictive model yielded an AUC value of 0.89 (95% CI: 0.858, 0.922) on the independent image set. AUC values of 0.88 (95% CI: 0.845, 0.926) and 0.90 (95% CI: 0.837, 0.940) were obtained for mass lesions only and non-mass lesions only, respectively. Compared with actual clinical management decisions, the predictive model achieved 99.5% sensitivity with 9.6% fewer recommended biopsies.

Conclusion

On an independent, consecutive clinical dataset within a single institution, a trained machine learning system yielded promising performance in distinguishing between malignant and benign breast lesions.
Age-related injury risk curves for the lumbar spine for use in low-back-pain prevention in manual handling tasks
Authors: Kudo Naoki , Yamada Yoji , Ito Daisuke
Published: September 2019

This study introduces injury risk curves for the lumbar spine for use in the risk assessment of low back pain (LBP) caused by manual lifting of heavy loads. LBP has been a longstanding problem among industrial workers, giving rise to the development of assistive devices. However, quantitative evaluation methods to verify the safety of such devices have not yet been established. The notable biomechanical criterion of 3.4 kN of lumbar compressive force, defined by the National Institute for Occupational Safety and Health, applies only to young, healthy workers with a fixed risk level. This study on injury risk curves clarified the risk level of injury to the lumbar spine due to lumbar compressive force for individuals within a wide age range. The findings can be applied for the design and evaluation of assistive devices as well as the design of ergonomic guidelines for manual work.
T-Box20 inhibits osteogenic differentiation in adipose-derived human mesenchymal stem cells: the role of T-Box20 on osteogenesis
Authors: Mollazadeh Samaneh , Fazly Bazzaz Bibi Sedigheh , Neshati Vajiheh , de Vries Antoine A. F. , Naderi-Meshkin Hojjat , Mojarad Majid , Neshati Zeinab , Kerachian Mohammad Amin
Published: September 2019

Background

Skeletal development and its cellular function are regulated by various transcription factors. The T-box (Tbx) family of transcription factors have critical roles in cellular differentiation as well as heart and limbs organogenesis. These factors possess activator and/or repressor domains to modify the expression of target genes. Despite the obvious effects ofTbx20on heart development, its impact on bone development is still unknown.

Methods

To investigate the consequence by forcedTbx20expression in the osteogenic differentiation of human mesenchymal stem cells derived from adipose tissue (Ad-MSCs), these cells were transduced with a bicistronic lentiviral vector encodingTbx20and an enhanced green fluorescent protein.

Results

Tbx20gene delivery system suppressed the osteogenic differentiation of Ad-MSCs, as indicated by reduction in alkaline phosphatase activity and Alizarin Red S staining. Consistently, reverse transcription-polymerase chain reaction analyses showed thatTbx20gain-of-function reduced the expression levels of osteoblast marker genes in osteo-inductive Ad-MSCs cultures. Accordingly,Tbx20negatively affected osteogenesis through modulating expression of key factors involved in this process.

Conclusion

The present study suggests thatTbx20could inhibit osteogenic differentiation in adipose-derived human mesenchymal stem cells.
Metagenome of a polluted river reveals a reservoir of metabolic and antibiotic resistance genes
Authors: Mittal Parul , Prasoodanan PK Vishnu , Dhakan Darshan B. , Kumar Sanjiv , Sharma Vineet K.
Published: September 2019

Background

Yamuna, a major tributary of Ganga, which flows through the national capital region of Delhi, is among the major polluted rivers in India. The accumulation of various effluents, toxic chemicals, heavy metals, and increased organic load in the Yamuna directly affects the organisms that thrive inside or around this river. It also makes it an ideal site for studying the impact of pollution on the river microflora, which are sentinels of the water quality.

Results

In this study, the microbial community structure and functional diversity of the Yamuna river water was assessed from the New Delhi region. The community structure of Yamuna during pre-monsoon (June) was found to be significantly different from the post-monsoon (November) time, with Acinetobacter being the most abundant genus during June, and Aeromonas during November. The functional characterization revealed the higher abundance of Methyl-accepting chemotaxis protein in the river water, which could be important for the microbial chemosensory adaptation in the environment. A higher abundance of genes related to nitrogen and sulfur metabolism, metal tolerance, and xenobiotic degradation, and complete degradation pathways of aromatic compounds such as toluene, xylene, benzene and phenol were identified. Further, the results showed the presence of a pool of antibiotic resistance genes in the bacterial microbiome in the Yamuna alongside a large number of broad-spectrum antibiotics, such as carbapenemases and metallo-β-lactamases. Efflux mechanism of resistance was found to dominate among these microbes conferring multi-drug resistance. The Principal Coordinate Analysis of the taxonomic composition of the Yamuna River water with publicly available freshwater and sewage datasets revealed significant differences in the two Yamuna samples and a greater resemblance of pre-monsoon Yamuna sample to sewage sample owing to the higher pollution levels in Yamuna in the pre-monsoon time.

Conclusion

The metagenomic study of the Yamuna river provides the first insights on the bacterial microbiome composition of this large polluted river, and also helps to understand the dynamics in the community structure and functions due to seasonal variations. The presence of antibiotic resistance genes and functional insights on the metabolic potential of a polluted river microbiome are likely to have several applications in health, biotechnology and bioremediation.
Pattern of fin rays along the antero-posterior axis based on their connection to distal radials
Authors: Hamada Hiroki , Uemoto Toshiaki , Tanaka Yoshitaka , Honda Yuki , Kitajima Keiichi , Umeda Tetsuya , Kawakami Atsushi , Shinya Minori , Kawakami Koichi , Tamura Koji , Abe Gembu
Published: September 2019

Background

Teleost paired fins are composed of two endoskeletal domains, proximal and distal radials, and an exoskeletal domain, the fin ray. The zebrafish pectoral fin displays elaborately patterned radials along the anteroposterior (AP) axis. Radials are considered homologous to tetrapod limb skeletons, and their patterning mechanisms in embryonic development are similar to those of limb development. Nevertheless, the pattern along the AP axis in fin rays has not been well described in the zebrafish pectoral fin, although several recent reports have revealed that fin ray development shares some cellular and genetic properties with fin/limb endoskeleton development. Thus, fin ray morphogenesis may involve developmental mechanisms for AP patterning in the fin/limb endoskeleton, and may have a specific pattern along the AP axis.

Results

We conducted detailed morphological observations on fin rays and their connection to distal radials by comparing intra- and inter-strain zebrafish specimens. Although the number of fin rays varied, pectoral fin rays could be categorized into three domains along the AP axis, according to the connection between the fin rays and distal radials; additionally, the number of fin rays varied in the posterior part of the three domains. This result was confirmed by observation of the morphogenesis process of fin rays and distal radials, which showed altered localization of distal radials in the middle domain. We also evaluated the expression pattern oflhxgenes, which have AP patterning activity in limb development, in fin rays and during distal radial development and found these genes to be expressed during morphogenesis in both fin rays and distal radials.

Conclusion

The fin ray and its connection to the endoskeleton are patterned along the AP axis, and the pattern along the AP axis in the fin ray and the radial connection is constructed by the developmental mechanism related to AP patterning in the limb/fin bud. Our results indicate the possibility that the developmental mechanisms of fin rays and their connection are comparable to those of the distal element of the limb skeleton.
Large-scale narrative events in popular cinema
Authors: Cutting James E. , Armstrong Kacie L.
Published: September 2019

Most experiments in event perception and cognition have focused on events that are only a few minutes in length, and the previous research on popular movies is consistent with this temporal scope. Scenes are generally between a few seconds and a few minutes in duration. But popular movies also offer an opportunity to explore larger events—variously called acts, major parts, or large-scale parts by film theorists—in which the boundaries often have few if any unique physical attributes. These units tend to be between about 20 to 35 min in duration. The present study had observers watch seven movies they had not seen before and, over the course of several days and with ample justifications, reflect on them, and then segment them into two to six parts with the aid of a running description of the narrative. Results showed consistency across viewers’ segmentations, consistency with film-theoretic segmentations, and superiority over internet subjects who had access to only the scenarios used by the movie viewers. Thus, these results suggest that there are large scale events in movies; they support a view that their events are organized meronomically, layered with units of different sizes and with boundaries shared across layers; and they suggest that these larger-scale events can be discerned through cognitive, not perceptual, means.
Lower limb weakness with gyrus rectus hematoma: an unusual presentation of paraclinoid aneurysm; a case report with review of literature
Authors: Patankar Amey P. , Vaja Maulik
Published: September 2019

Lower limb weakness is usually a feature of ruptured anterior communicating (ACom) aneurysms due to spasm of the anterior cerebral arteries. Paraclinoid aneurysms, in addition to other cardinal features of subarachnoid haemorrhage (SAH), usually present with headache and visual field defects due to compression of the optic pathway. We report a case of left paraclinoid aneurysm presenting with right lower limb weakness and gyrus rectus hematoma without SAH. The aneurysm was long, passing beneath the optic nerve to emerge in the inter-optic cistern, leading to such atypical presentation. The aneurysm was clipped successfully after drilling the clinoid. As per our knowledge, such a clinical presentation of paraclinoid aneurysm has not been reported in the literature till date.
Effect of Psychological Intervention on Fear of Cancer Recurrence: A Systematic Review and Meta-Analysis
Authors: Tauber Nina M. , O’Toole Mia S. , Dinkel Andreas , Galica Jacqueline , Humphris Gerry , Lebel Sophie , Maheu Christine , Ozakinci Gozde , Prins Judith , Sharpe Louise , Smith Allan “Ben” , Thewes Belinda , Simard Sébastien , Zachariae Robert
Published: September 2019

PURPOSE

Fear of cancer recurrence (FCR) is a significantly distressing problem that affects a substantial number of patients with and survivors of cancer; however, the overall efficacy of available psychological interventions on FCR remains unknown. We therefore evaluated this in the present systematic review and meta-analysis.

METHODS

We searched key electronic databases to identify trials that evaluated the effect of psychological interventions on FCR among patients with and survivors of cancer. Controlled trials were subjected to meta-analysis, and the moderating influence of study characteristics on the effect were examined. Overall quality of evidence was evaluated using the GRADE system. Open trials were narratively reviewed to explore ongoing developments in the field (PROSPERO registration no.: CRD42017076514).

RESULTS

A total of 23 controlled trials (21 randomized controlled trials) and nine open trials were included. Small effects (Hedges’s g) were found both at postintervention ( g = 0.33; 95% CI, 0.20 to 0.46; P < .001) and at follow-up ( g = 0.28; 95% CI, 0.17 to 0.40; P < .001). Effects at postintervention of contemporary cognitive behavioral therapies (CBTs; g = 0.42) were larger than those of traditional CBTs ( g = 0.24; β = .22; 95% CI, .04 to .41; P = .018). At follow-up, larger effects were associated with shorter time to follow-up (β = −.01; 95% CI, −.01 to −.00; P = .027) and group-based formats (β = .18; 95% CI, .01 to .36; P = .041). A GRADE evaluation indicated evidence of moderate strength for effects of psychological intervention for FCR.

CONCLUSION

Psychological interventions for FCR revealed a small but robust effect at postintervention, which was largely maintained at follow-up. Larger postintervention effects were found for contemporary CBTs that were focused on processes of cognition—for example, worry, rumination, and attentional bias—rather than the content, and aimed to change the way in which the individual relates to his or her inner experiences. Future trials could investigate how to further optimize and tailor interventions to individual patients’ FCR presentation.
Pembrolizumab in Relapsed and Refractory Mycosis Fungoides and Sézary Syndrome: A Multicenter Phase II Study
Authors: Khodadoust Michael S. , Rook Alain H. , Porcu Pierluigi , Foss Francine , Moskowitz Alison J. , Shustov Andrei , Shanbhag Satish , Sokol Lubomir , Fling Steven P. , Ramchurren Nirasha , Pierce Robert , Davis Asa , Shine Richard , Li Shufeng , Fong Sophia , Kim Jinah , Yang Yi , Blumenschein Wendy M. , Yearley Jennifer H. , Das Biswajit , Patidar Rajesh , Datta Vivekananda , Cantu Erin , McCutcheon Justine N. , Karlovich Chris , Williams P. Mickey , Subrahmanyam Priyanka B. , Maecker Holden T. , Horwitz Steven M. , Sharon Elad , Kohrt Holbrook E. , Cheever Martin A. , Kim Youn H.
Published: September 2019

PURPOSE

To assess the efficacy of pembrolizumab in patients with advanced relapsed or refractory mycosis fungoides (MF) or Sézary syndrome (SS).

PATIENTS AND METHODS

CITN-10 is a single-arm, multicenter phase II trial of 24 patients with advanced MF or SS. Patients were treated with pembrolizumab 2 mg/kg every 3 weeks for up to 24 months. The primary end point was overall response rate by consensus global response criteria.

RESULTS

Patients had advanced-stage disease (23 of 24 with stage IIB to IV MF/SS) and were heavily pretreated with a median of four prior systemic therapies. The overall response rate was 38% with two complete responses and seven partial responses. Of the nine responding patients, six had 90% or more improvement in skin disease by modified Severity Weighted Assessment Tool, and eight had ongoing responses at last follow-up. The median duration of response was not reached, with a median response follow-up time of 58 weeks. Immune-related adverse events led to treatment discontinuation in four patients. A transient worsening of erythroderma and pruritus occurred in 53% of patients with SS. This cutaneous flare reaction did not result in treatment discontinuation for any patient. The flare reaction correlated with high PD-1 expression on Sézary cells but did not associate with subsequent clinical responses or lack of response. Treatment responses did not correlate with expression of PD-L1, total mutation burden, or an interferon-γ gene expression signature.

CONCLUSION

Pembrolizumab demonstrated significant antitumor activity with durable responses and a favorable safety profile in patients with advanced MF/SS.
Potentially Every Culture Is All Cultures
Authors: Feyerabend Paul
Published: September 2019

With a focus on the role of Achilles in the Iliad, this essay argues that it is a mistake to assume that languages and cultures are closed totalities impervious to influence from the outside and from internally driven transformations. If we eliminate that assumption, several others likewise become untenable, including the assumption that precise meanings for words or concepts are available in principle. Objectivism and relativism are claimed to be equally chimerical.
The Historians’ Preposterous Project
Authors: Clendinnen Inga
Published: September 2019

Contrasting its author’s microhistorical approach with other historical methodologies, especially that of Keith Thomas, Clendinnen praises Kirsten McKenzie’s A Swindler’s Progress: Nobles and Convicts in the Age of Liberty (Cambridge, MA: Harvard University Press, 2010) for deftly tying the apparently idiosyncratic stories of a transported convict and the noble family whose scion he impersonated to more pervasive dynamics in nineteenth-century British imperial culture.
Rethinking “Normative Conscience”
Authors: Kristeva Julia
Published: September 2019

Written originally as part of a Common Knowledge symposium (2007) responding to Cardinal Joseph Ratzinger’s homily against relativism, which was delivered immediately before his election as pope, this essay describes a reactionary German intellectual current that includes not only Ratzinger and the conservative jurist E.-W. Böckenförde but also the more liberal philosopher Jürgen Habermas. What the three share, according to Kristeva, is their assessment of “rationalist humanism” as incapable of sustaining constitutional democracies, which by nature “need ‘normative presuppositions’ [on which] to found rational law.” In an effort to “counterbalance this hypothesis,” she argues that “we are already confronted with . . . experiences that render obsolete any appeal for a normative conscience.” These experiences comprise discoveries of the modern human sciences above all psychoanalysis and literary theory, which “are likely to found the ‘unifying bond’ that secular, political rationality has until now lacked.” Thus, she concludes, “modern thought, which is neither hostile nor indulgent toward religion, may be our one good option as we face, on the one hand, mounting obscurantism and, on the other, the technological management of the human species.”
Une Machine à Penser
Authors: Ginzburg Carlo
Published: September 2019

The author describes his research experience in the 1960s as an apprentice historian in the Warburg Library. His work on witchcraft trials in early modern Italy, he argues, was deeply affected by the library’s unique character. Aby Warburg’s law of the “good neighbor” (the book we need is placed next to the one we are looking for) is illustrated through a specific example: the encounter with a forgotten tract dealing with some anomalous Bavarian witchcraft trials — a book that would have been very difficult (if not impossible) to come across anywhere but Warburg’s Library.
On How Postwar Germany Has Faced Its Recent Past
Authors: Habermas Jürgen
Published: September 2019

In this essay Habermas contends that, until 1989, four phases are discernible in how postwar Germany attempted to come to terms with its “unmasterable past.” Between the end of the war in 1945 and the foundation of two German states in 1949, the first reconstruction generation mythologized the Nazi period as a criminal abyss. If this strategy allowed the government of the Federal Republic to assume legal responsibility for reparation claims, it also served to release individuals from working through their own painful pasts. This stage yielded to a second phase, one of “communicative silencing,” during the Adenauer years from 1949-63 in which the second reconstruction generation chose not to speak of the past but rather to concentrate on building the Wirtschaftswunder. The student movement of the 1960s challenged this presentism with demands for disclosure and accountability, and from the mid-1970s until 1989 this quest for unmasking existed in tension with an ongoing desire for evasion. This tension drove the “Historians’ Debate” of those years. Since reunification in 1989, Germany’s attitude toward its past has remained ambivalent. Today a New Right calls for the self-confident reassertion of a German nation unburdened by its past. But the past will lose its hold over Germany, Habermas argues, only through the work of a truly faithful memory.
Cosmopolitan
Authors: Jasanoff Maya
Published: September 2019

Written in an effort “to frame questions of culture and power in different terms” from those of Edward Said, this case study of Ottoman Alexandria before the French invasion in 1798 (identified by Said as the “launchpad of modern Orientalism”) reveals “lines between empowered and powerless, even East and West,” blurred or erased by “cosmopolitan mixing. . . . So much attention is paid to the way that empires divide people against each other that it is easy to forget how empires have also brought populations together, forcibly at times, yet often with enduring effects. The cosmopolitan possibilities of empire, as opposed to narrower definitions of national belonging, would shape the life of Etienne Roboly,” whose complicated existence in Egypt—as a citizen of both or neither the French state and/nor the Ottoman—is the focus of this study. The author asks her readers to glean from this article two “lessons”: first, that “nation-states, as the briefest glance at twentieth-century history will confirm, have often proved themselves hostile toward minority populations. Yet we have also been taught to see empires as evil things, which makes the second lesson— that empires have sometimes been more accommodating of difference than many independent nations—seem somewhat counterintuitive. . . . The history of Alex-andria invites us to look at how empire may provide an umbrella of common security for a range of cultures to coexist, and even at times intermingle.” Still, “the larger question is whether and how inclusionary definitions of belonging can be made to oughtweigh exclusionary ones,” regardless of the political context.
Two Hundred Years Together
Authors: Solzhenitsyn Alexander
Published: September 2019

This essay is a translated excerpt from the first volume of Solzhenitsyn’s controversial history of Russian-Jewish relations, Dvesti let vmeste: 1795 – 1995, which was first published in Russian in 2001 and 2002. Solzhenitsyn writes from explicitly nationalist positions, ascribing defined identities and “fates” to disparate peoples, and seeks to offer a “two-sided and equitable” account of the “sins” and historical “guilt” of both Russians and Jews. He seeks to establish “mutually accessible and benevolent paths along which Russian-Jewish relations may proceed” on the basis of an honest and full accounting of history. In this excerpt he treats the immediate prerevolutionary period of the early twentieth century, drawing on the writings of a number of prominent commentators of that period, both Jewish and Russian. He argues that a combination of, on the one hand, the investments of the progressive Russian intelligentsia in atonement for anti-Semitic policies and social violence, and, on the other, Jewish assimilation to Russian cultural life led to an identification of Jews with revolutionary and anti-tsarist culture. Among the figures treated here by Solzhenitsyn are Vladimir Jabotinsky, Lev Tolstoi, Nikolai Berdiaev, and Pyotr Struve.
Zebrafish prmt5 arginine methyltransferase is essential for germ cell development
Authors: Zhu Junji , Zhang Dawei , Liu Xing , Yu Guangqing , Cai Xiaolian , Xu Chenxi , Rong Fangjing , Ouyang Gang , Wang Jing , Xiao Wuhan
Published: September 2019

Protein arginine methyltransferase 5 (Prmt5), a type II arginine methyltransferase, symmetrically dimethylates arginine in nuclear and cytoplasmic proteins. Prmt5 is involved in a variety of cellular processes including ribosome biogenesis, cellular differentiation, germ cell development, and tumorigenesis. However, the mechanisms by which prmt5 influences cellular processes have remained unclear. Here, prmt5 loss in zebrafish led to the expression of an infertile male phenotype due to a reduction in germ cell number, an increase in germ cell apoptosis, and the failure of gonads to differentiate into normal testes or ovaries. Moreover, arginine methylation of the germ-cell-specific proteins Zili and Vasa, as well as histones H3 (H3R8me2s) and H4 (H4R3me2s), was reduced in the gonads of prmt5-null zebrafish. This resulted in the downregulation of several Piwi pathway proteins, including Zili, and Vasa. In addition, various genes related to meiosis, gonad development, and sexual differentiation were dysregulated in the gonads of prmt5-null zebrafish. Our results revealed a novel mechanism associated with prmt5, i.e., prmt5 apparently controls germ cell development in vertebrates by catalyzing arginine methylation of the germline-specific proteins Zili and Vasa.
Invadopodia-mediated ECM degradation is enhanced in the G1 phase of the cell cycle
Authors: Bayarmagnai Battuya , Perrin Louisiane , Esmaeili Pourfarhangi Kamyar , Graña Xavier , Tüzel Erkan , Gligorijevic Bojana
Published: September 2019

The process of tumor cell invasion and metastasis includes assembly of invadopodia, protrusions capable of degrading the extracellular matrix (ECM). The effect of cell cycle progression on invadopodia has not been elucidated. In this study, by using invadopodia and cell cycle fluorescent markers, we show in 2D and 3D cultures, as well as in vivo, that breast carcinoma cells assemble invadopodia and invade into the surrounding ECM preferentially during the G1 phase. The expression (MT1-MMP, also known as MMP14, and cortactin) and localization (Tks5; also known as SH3PXD2A) of invadopodia components are elevated in G1 phase, and cells synchronized in G1 phase exhibit significantly higher ECM degradation compared to the cells synchronized in S phase. The cyclin-dependent kinase inhibitor (CKI) p27kip1 (also known as CDKN1B) localizes to the sites of invadopodia assembly. Overexpression and stable knockdown of p27kip1 lead to contrasting effects on invadopodia turnover and ECM degradation. Taken together, these findings suggest that expression of invadopodia components, as well as invadopodia function, are linked to cell cycle progression, and that invadopodia are controlled by cell cycle regulators. Our results caution that this coordination between invasion and cell cycle must be considered when designing effective chemotherapies.
Impact of movement and motion-artefact correction on image quality and interpretability in CBCT units with aligned and lateral-offset detectors
Authors: Santaella Gustavo Machado , Wenzel Ann , Haiter-Neto Francisco , Rosalen Pedro Luiz , Spin-Neto Rubens
Published: September 2019

Objectives:

To evaluate the impact of movement and motion-artefact correction systems on CBCT image quality and interpretability of simulated diagnostic tasks for aligned and lateral-offset detectors.

Methods:

A human skull simulating three diagnostic tasks (implant planning in the anterior maxilla, implant planning in the left-side-mandible and mandibular molar furcation assessment in the right-side-mandible) was mounted on a robot performing six movement types. Four CBCT units were used: Cranex 3Dx (CRA), Ortophos SL (ORT), Promax 3D Mid (PRO), and X1. Protocols were tested with aligned (CRA, ORT, PRO, and X1) and lateral-offset (CRA and PRO) detectors and two motion-artefact correction systems (PRO and X1). Movements were performed at one moment-in-time (t1), for units with an aligned detector, and three moments-in-time (t1-first-half of the acquisition, t2-second-half, t3-both) for the units with a lateral-offset detector. 98 volumes were acquired. Images were scored by three observers, blinded to the unit and presence of movement, for motion-related stripe artefacts, overall unsharpness, and interpretability. Fleiss’ κ was used to assess interobserver agreement.

Results:

Interobserver agreement was substantial for all parameters (0.66–0.68). For aligned detectors, in all diagnostic tasks a motion-artefact correction system influenced image interpretability. For lateral-offset detectors, the interpretability varied according to the unit and moment-in-time, in which the movement was performed. PRO motion-artefact correction system was less effective for the offset detector than its aligned counterpart.

Conclusion:

Motion-artefact correction systems enhanced image quality and interpretability for units with aligned detectors but were less effective for those with lateral-offset detectors.
Procedural Justice and the Risks of Consumer Voting
Authors: Kim Tami , John Leslie K. , Rogers Todd , Norton Michael I.
Published: September 2019

Firms are increasingly giving consumers the vote. Eight studies show that, when firms empower consumers to vote, consumers infer a series of implicit promises—even in the absence of explicit promises. We identify three implicit promises to which consumers react negatively when violated: representation (Experiments 1A–1C), consistency (Experiment 2), and nonsuppression (Experiment 3). However, when firms honor these implicit promises, voting can mitigate the disappointment that arises from receiving an undesired outcome (Experiment 4). Finally, Experiment 5 identifies one instance when suppressing the vote outcome is condoned: when voters believe that the process of voting has resulted in an unacceptable outcome. More generally, we show that procedural justice plays a key mediating role in determining the relative success or failure of various empowerment initiatives—from soliciting feedback to voting. Taken together, we offer insight into how firms can realize the benefits of empowerment strategies while mitigating their risks.

This paper was accepted by Elke Weber, judgment and decision making.
La invisibilización de la evasión de impuestos en el agro cordobés: tres técnicas de inmuno-ocultamiento
Authors: Comba Antonella
Published: September 2019

En este artículo nos dedicamos a examinar las operaciones socioculturales por medio de las cuales se margina —al punto que se oculta e invisibiliza— la evasión de impuestos en la producción agrícola cordobesa en el discurso social por medio de tres operaciones sociodiscursivas que llamamos «técnicas de inmuno-ocultamiento». El objetivo es explicar la falta de criminalización social y/o la ausencia de sentimientos de condena y repudio hacia la evasión de impuestos en el agro por parte del imaginario de todos aquellos que se inscriben en la ruralidad cordobesa. Para ello, realizamos treinta entrevistas en profundidad a distintos actores sociales del agro cordobés que trabajamos a partir de los lineamientos de la teoría fundamentada. Analizamos el material cualitativo a partir de un andamiaje conceptual propio de las Ciencias Sociales que se nutre de los aportes de Michel Foucault, la «Criminología Crítica» y la «Criminología Rural».