bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Synergistic Anticancer FAK and HDAC Inhibitor Combination Discovered by a Novel Chemical–Genetic High-Content Phenotypic Screen
Authors: Dawson John C. , Serrels Bryan , Byron Adam , Muir Morwenna T. , Makda Ashraff , García-Muñoz Amaya , von Kriegsheim Alex , Lietha Daniel , Carragher Neil O. , Frame Margaret C. 
Published: November 2019

Abstract
We mutated the focal adhesion kinase (FAK) catalytic domain to inhibit binding of the chaperone Cdc37 and ATP, mimicking the actions of a FAK kinase inhibitor. We reexpressed mutant and wild-type FAK in squamous cell carcinoma (SCC) cells from which endogenous FAK had been deleted, genetically fixing one axis of a FAK inhibitor combination high-content phenotypic screen to discover drugs that may synergize with FAK inhibitors. Histone deacetylase (HDAC) inhibitors represented the major class of compounds that potently induced multiparametric phenotypic changes when FAK was rendered kinase-defective or inhibited pharmacologically in SCC cells. Combined FAK and HDAC inhibitors arrest proliferation and induce apoptosis in a subset of cancer cell lines in vitro and efficiently inhibit their growth as tumors in vivo. Mechanistically, HDAC inhibitors potentiate inhibitor-induced FAK inactivation and impair FAK-associated nuclear YAP in sensitive cancer cell lines. Here, we report the discovery of a new, clinically actionable, synergistic combination between FAK and HDAC inhibitors.
A Novel Sulforaphane-Regulated Gene Network in Suppression of Breast Cancer–Induced Osteolytic Bone Resorption
Authors: Pore Subrata K. , Hahm Eun-Ryeong , Kim Su-Hyeong , Singh Krishna B. , Nyiranshuti Lea , Latoche Joseph D. , Anderson Carolyn J. , Adamik Juraj , Galson Deborah L. , Weiss Kurt R. , Watters Rebecca J. , Lee Boeun , Kumta Prashant N. , Singh Shivendra V. 
Published: November 2019

AbstractBone is the most preferred site for colonization of metastatic breast cancer cells for each subtype of the disease. The standard of therapeutic care for breast cancer patients with bone metastasis includes bisphosphonates (e.g., zoledronic acid), which have poor oral bioavailability, and a humanized antibody (denosumab). However, these therapies are palliative, and a subset of patients still develop new bone lesions and/or experience serious adverse effects. Therefore, a safe and orally bioavailable intervention for therapy of osteolytic bone resorption is still a clinically unmet need. This study demonstrates suppression of breast cancer–induced bone resorption by a small molecule (sulforaphane, SFN) that is safe clinically and orally bioavailable. In vitro osteoclast differentiation was inhibited in a dose-dependent manner upon addition of conditioned media from SFN-treated breast cancer cells representative of different subtypes. Targeted microarrays coupled with interrogation of The Cancer Genome Atlas data set revealed a novel SFN-regulated gene signature involving cross-regulation of runt-related transcription factor 2 (RUNX2) and nuclear factor-κB and their downstream effectors. Both RUNX2 and p65/p50 expression were higher in human breast cancer tissues compared with normal mammary tissues. RUNX2 was recruited at the promotor of NFKB1. Inhibition of osteoclast differentiation by SFN was augmented by doxycycline-inducible stable knockdown of RUNX2. Oral SFN administration significantly increased the percentage of bone volume/total volume of affected bones in the intracardiac MDA-MB-231-Luc model indicating in vivo suppression of osteolytic bone resorption by SFN. These results indicate that SFN is a novel inhibitor of breast cancer–induced osteolytic bone resorption in vitro and in vivo.
Carotid Intima-Media Thickness
Authors: Strawbridge Rona J. , Ward Joey , Bailey Mark E.S. , Cullen Breda , Ferguson Amy , Graham Nicholas , Johnston Keira J.A. , Lyall Laura M. , Pearsall Robert , Pell Jill , Shaw Richard J. , Tank Rachana , Lyall Donald M. , Smith Daniel J. 
Published: December 2019

Objective:
Atherosclerosis is the underlying cause of most cardiovascular disease, but mechanisms underlying atherosclerosis are incompletely understood. Ultrasound measurement of the carotid intima-media thickness (cIMT) can be used to measure vascular remodeling, which is indicative of atherosclerosis. Genome-wide association studies have identified many genetic loci associated with cIMT, but heterogeneity of measurements collected by many small cohorts have been a major limitation in these efforts. Here, we conducted genome-wide association analyses in UKB (UK Biobank; N=22 179), the largest single study with consistent cIMT measurements.

Approach and Results:

We used BOLT-LMM software to run linear regression of cIMT in UKB, adjusted for age, sex, and genotyping chip. In white British participants, we identified 5 novel loci associated with cIMT and replicated most previously reported loci. In the first sex-specific analyses of cIMT, we identified a locus on chromosome 5, associated with cIMT in women only and highlight
VCAN
as a good candidate gene at this locus. Genetic correlations with body mass index and glucometabolic traits were also observed. Two loci influenced risk of ischemic heart disease.

ConclusionS:
These findings replicate previously reported associations, highlight novel biology, and provide new directions for investigating the sex differences observed in cardiovascular disease presentation and progression.
Description of Longidorus barsii Radivojević & De Luca sp. n. (Nematoda: Longidoridae) from Serbia and observations on some taxonomic characters
Authors: Radivojević Milan , Barsi László , Fanelli Elena , De Luca Francesca 
Published: November 2019

Summary
Longidorus barsii sp. n., from Mt Tara in the Balkan Peninsula, is described and characterised by using a polyphasic approach. The species has numerous males. The female body is 5-7 mm long, rather stout and resembles a large Xiphinema. The lip region is wide, with rounded sides continuous with the neck, frontally flattened and depressed around the oral aperture, amphids are pouch-like and distinctly bi-lobed and the odontostyle is moderately long. The nuclei of the pharyngeal glands are in the normal position, the dorsal nucleus located somewhat posterior to anterior third of bulb. The uteri are long, the distal inner epithelium densely covered with papilla-like outgrowths. The tail is rounded, bluntly conoid and very short. Alpha-numerical identification codes: A4/5, B45, C3, D3, E2, F3, G 1(2), H1, I2, J1, K67. The morphologically most similar species are L. kheirii, L. polyae and L. profundorum. Additional observations are provided on the anterior body region and genital organs in L. barsii sp. n., L. piceicola, L. silvae, and L. uroshis. Selected features are discussed from the taxonomic and functional points of view. The D2-D3 expansion domains of the 28S rRNA gene and the ITS region of L. barsii sp. n. were amplified and sequenced. Phylogenetic analysis using the D2-D3 expansion domains of the 28S rRNA gene revealed close evolutionary relationships with L. polyae, L. athesinus and three unidentified Longidorus spp.
Marxism, Structuralism and Psychoanalysis
Authors: Starcenbaum Marcelo 
Published: November 2019

Abstract
Althusser’s reception within Argentinian psychoanalytic culture assumed a variety of different forms. For the purposes of delimiting mediations between Marxism, structuralism and psychoanalysis in Argentina during the 1960s and ’70s, this work seeks to reconstruct historical readings of Althusser according to his reception within three distinct interpretative communities. The first group, centring on the figure of Oscar Masotta, concerns Althusser’s role in the development of Argentina’s incipient Lacanian groups. For the second group, primarily dissident-psychoanalytic and Freudo-Marxist, the reception of Althusser will be considered in tandem with ensuing debates between Freudo-Marxism and Althussero-Lacanism. The third group asks us to consider the role of Althusserianism in discussions around the professionalisation of psychology, where the careers of Carlos Sastre and Roberto Harari showed the strongest connections to Althusser’s work.
Contradictions of the Labour Process, Worker Empowerment and Capitalist Inefficiency
Authors: Vidal Matt 
Published: November 2019

Abstract
I articulate a classical-Marxist theory of technical change in the capitalist labour process, highlighting two contradictions. The management contradiction is the conflict managers experience between coordination (to increase efficiency) and discipline (to ensure valorisation). The workforce contradiction is the tension workers experience between productive socialisation and alienation. I submit that both contradictions were substantially muted from the earliest stages of capitalism through the Fordist stage but have become intensified in the postfordist period. Under postfordism, the basis of efficiency is economies of scope and flexibility, and thus there is a real efficiency advantage to empowering workers, via both multiskilling and employee involvement in problem-solving and decision-making. Postfordist capitalism has thus initiated an intensification of the management and workforce contradictions. In response, capitalist management is increasingly impeding the growth of the productive forces by failing to empower workers.
The Bad, The Wrong, and The Unjust: A Comment on Rondel’s Pragmatist Egalitarianism
Authors: Talisse Robert B. 
Published: November 2019

In his Pragmatist Egalitarianism, David Rondel proposes a “pluralist egalitarianism” as a pragmatist resolution to longstanding debates over egalitarian justice. On Rondel’s view, egalitarianism has three distinct and irreducible variables. In this comment, I argue that pluralist views generally do not reconcile anything, but instead posit sites of normative conflict that are in principle invulnerable to remediation by human intelligence. I then propose that although Rondel might be correct to identify three distinct sites of egalitarian concern, there remains reason to prioritize what he calls the “institutional” variable.
From the Fragments Up: Municipal Margins of Maneuver in Syria and Tunisia
Authors: Salman Lana , Baird-Zars Bernadette 
Published: November 2019

Most studies of the Arab uprisings and their aftermaths focus on national-level political processes, neglecting changes at the municipal level. The few studies of municipalities that do exist tend to treat municipalities either as corruption-prone institutions exploited by local elites, or else as areas in need of intervention to make them function properly. We argue that municipalities are an overlooked site of political change—both spatially and temporally—that began prior to the uprisings but accelerated in their aftermath. Drawing on original empirical material from Tunisia and Syria between 2007 and 2014, we highlight two changing dimensions of municipal governance: how municipalities have sought to expand their power by stretching into new areas; and how, since the uprisings, municipalities have taken up new regulatory and enforcement roles in the wake of central state retreat.
To support this analysis, we utilize on-the-ground interviews and fieldwork in Tunisia and off-site interviews and aerial analyses of urban growth in northern Syria. We find that, first, city governments are moving into the spaces where national actors are absent, transforming municipalities into spaces for meaningful political engagement (Tunisia) and the allocation of resources (Syria). Second, municipalities have gained greater autonomy in the arenas of service delivery and planning. This increase in municipal power does not represent a break from pre-uprising practices, but rather a continuation and perhaps acceleration of the politicization and expansion of municipal authority that began pre-2011.
Word families, allofams, and the comparative method
Authors: FELLNER Hannes A. , HILL Nathan W. 
Published: November 2019

Abstract
Linguists researching the Trans-Himalayan family do not have a self-perception as working outside the mainstream of historical linguistics, but ‘word families’ and ‘allofams’ are important elements in their thinking despite the absence of these terms in the wider discipline. A close examination of the practice of historical linguistics in Indo-European and Trans-Himalayan leads to the conclusion that those phenomena treated as word families admit superior analyses in more traditional terms.
On the event structure of Chinese resultative compounds
Authors: BASCIANO Bianca 
Published: November 2019

Abstract
It has been observed that Chinese resultative compounds display varied aspectual behaviors. Yong (1997) distinguishes between simple change resultatives, i.e. resultatives expressing instantaneous change, but allowing a process preliminary to the final change, and complex change resultatives, i.e. those allowing a gradual development of action. Starting from this distinction, this paper aims at providing a structural account of these resultative compounds, based on the constructionist framework put forth by Ramchand (2008), arguing that only simple change resultatives are characterized by having a result layer in their eventive structure. Complex change resultatives, in contrast, are characterized by having the result element in the complement position of the process projection, providing a scalar path. This allows a gradual change of state, and telicity emerges when the path is bounded. The paper also discusses the relation between complex change resultatives and degree achievements.
A brief response to Fellner and Hill’s “Word families, allofams, and the comparative method”
Authors: HANDEL Zev 
Published: November 2019

Abstract
In a recent article, Fellner & Hill (this volume) level a strong critique against what they view as the misguided prevailing methodology of historical-comparative reconstruction in the Sino-Tibetan (aka Trans-Himalayan) language family. The central focus of their criticism is the assembling of “word families” and the reconstruction of ST proto-forms exhibiting variation to account for those word families. In this response, I argue that the methodology is basically sound and is appropriate to the current state of our knowledge. At the same time, I dispute some of the assertions made by Fellner & Hill, which I believe are mischaracterizations of the methods and assumptions underlying the work of Sino-Tibetan scholars.
The differing status of reconstruction in Trans-Himalayan and Indo-European
Authors: FELLNER Hannes A. , HILL Nathan W. 
Published: November 2019

Abstract
The replies to Fellner and Hill (this volume) present the practice of historical linguistics in the study of the Trans-Himalayan family as on the trail our Indo-European forbears blazed. The replies further present “word families” and “allofams” as beacons that light this path; we disagree. Our respondents overlook the different status of reconstructions in the two families. Research at the subgroup level that they point to as Neogrammarian implements a formalist approach to reconstruction, which, fine as far as it goes, lacks the sophistication of reconstructions in more mature disciplines. Not appreciating the different status of reconstruction in the two families, our respondents exaggerate the extent to which Indo-European evinces “word family”-like phenomena and present allofams as more synchronically plausible than they are.
A review of Fellner and Hill’s “Word families, allofams, and the comparative method”
Authors: THURGOOD Graham 
Published: November 2019

Abstract
Fellner and Hill (this volume) argue that the recourse to the notion of word families has prevented scholars specializing in Sino-Tibetan comparative linguistics from working out regular sound correspondences. This paper disputes this evaluation of the state of the art in the field, and suggests that F&H’s appraisal is due to severe misunderstandings.
On Tán/Tán Distinction in Modern Xiang Dialects and the Reconstruction in Proto Xiang
Authors: Wu Rui-wen 
Published: November 2019

According to Qièyùn, Tán (覃) and Tán (談) are two distinct rhymes, i.e. double rhyme, in Xián Shè Grade I. From the historical Chinese phonology perspective, the Northern people who spoke the Northern dialect started merging Tán / Tán distinction at early Tang Dynasty but, relatively, the Southern people retained it. In other words, Tán / Tán distinction is an important phonological feature to divide the early Chinese dialects into Northern group and Southern group. Recent researches shows that Tán / Tán distinction still obtain in modern Chinese dialects, such as Wú, Mĭn and Gàn dialects. However, the question ‘if Tán / Tán distinction obtains in modern Xiang dialect’ is under debate until now. This article would like to examine 12 modern Xiang dialects and explore the phenomena and phonological contrast in Xiang dialects. Furthermore, this article also tried to reconstruction the proto forms for Tán / Tán rhymes. This article not only focused on the phonological contrast provided by Qièyùn framework but also noticed the colloquial lexicons, which retained the early distinction. The main conclusions are as follows:1.From the viewpoint of phonological contrast, only one kind of Xiang dialect subcategories, i.e. Lóu-Shào Piàn, obtains Tán / Tán distinction. The distinction has been dropped in Cháng Yì Piàn and Xù Pŭ Piàn.2.From the viewpoint of colloquial lexicon, there are still four lexicons with Tán / Tán distinction. Those lexicons are distributed in modern Xiang dialects more or less. 3. From the viewpoint of historical linguistics, the Tán (覃) rhyme after velar initials could be reconstructed as *-oN and *-oʔ and the Tán (談) rhyme as *ɑN and *ɑʔ after the same initial environment. It shows that Tán / Tán distinction is partially remained in Xiang dialects. The main vowel *-o in *oN and *-oɁ finals tends to vowel breaking and so the reflections of *oN and *oʔ in modern Xiang dialects include -uẽ, -uɛ̃, -ua and -ue etc.
What Is the Maximum Entropy Principle? Comments on “Statistical Theory on the Functional Form of Cloud Particle Size Distributions”
Authors: Yano Jun-Ichi 
Published: December 2019

Abstract
The basic idea of the maximum entropy principle is presented in a succinct, self-contained manner. The presentation points out some misunderstandings on this principle by Wu and McFarquhar. Namely, the principle does not suffer from the problem of a lack of invariance by change of the dependent variable; thus, it does not lead to a need to introduce the relative entropy as suggested by Wu and McFarquhar. The principle is valid only with a proper choice of a dependent variable, called a restriction variable, for a distribution. Although different results may be obtained with the other variables obtained by transforming the restriction variable, these results are simply meaningless. A relative entropy may be used instead of a standard entropy. However, the former does not lead to any new results unobtainable by the latter.
What Neuromonitoring Changes Can Be Expected During Hip Arthroscopy in the Pediatric Population?
Authors: Shelton Trevor J. , Patel Akash , Agatstein Lauren , Haus Brian M. 
Published: December 2019

Background: As its indications have evolved, hip arthroscopy is now performed more frequently in pediatric patients. However, despite this increase, there is a lack of evidence in the literature about its safety in this population in regard to traction injury of the nerves of the lower extremity. Purpose: To determine neuromonitoring changes of the sciatic, femoral, and obturator nerves during hip arthroscopy in the pediatric population and determine the rate of and risk factors for clinical neurapraxia. Study Design: Case series; Level of evidence, 4. Methods: A retrospective review was performed of all pediatric patients who underwent hip arthroscopy with neuromonitoring from December 2013 to October 2018. Neuromonitoring included somatosensory evoked potentials (SSEPs) in the peroneal and posterior tibial nerves and electromyography (EMG) signal for the obturator, femoral, and peroneal and posterior tibial nerves. Traction was applied using a radiolucent traction table. We recorded total traction time, surgery time, SSEP changes >50% after traction application, and EMG activity. We also recorded whether there was a clinical neurapraxia and when nerve function returned, and analyzed surgical and patient characteristic data for risk factors for neurapraxia. Results: A total of 89 patients had hip arthroscopy (median traction time, 69 minutes). SSEP changes >50% occurred in 78% of patients in the peroneal nerve and 73% in the posterior tibial nerve. EMG activity was observed in 9% of patients in the obturator nerve, 8% in the femoral nerve, 12% in the peroneal nerve, and 8% in the posterior tibial nerve. Clinical neurapraxia was seen in 19% of patients in either the peroneal nerve or posterior tibial nerve but resolved by 2 days postoperatively. Those who sustained a neurapraxia had a 32-minute longer surgery and 6-minute longer traction time. The clinical rate of neurapraxia of the pudendal nerve was 0%. Conclusion: Neuromonitoring changes are common during hip arthroscopy and nearly 1 in 5 pediatric patients will have some decreased sensation in either the peroneal or the posterior tibial nerve that resolves within 1 to 2 days after surgery. In pediatric patients, longer surgery and traction times during hip arthroscopy are associated with a higher rate of neurapraxia than that reported for adults.
Frequency of biotinidase gene variants and incidence of biotinidase deficiency in the Newborn Screening Program in Minas Gerais, Brazil
Authors: Carvalho Nara de Oliveira , Januário José Nélio , Felix Gilsimary Lessa Pereira , Nolasco Daniela Magalhães , Ladeira Roberto Vagner Puglia , del Castillo Dora Mendes , Starling Ana Lúcia Pimenta , Norton Rocksane de Carvalho , Viana Marcos Borato 
Published: December 2019

Objective The prevalence of biotinidase deficiency and the frequency of biotinidase gene variants in Brazil are not documented. We aimed to determine the incidence of partial and profound biotinidase deficiency in the state of Minas Gerais, Brazil, and to calculate the frequency of biotinidase gene variants in the newborn screening program of Minas Gerais. Methods Neonates (1,168,385) were screened from May 2013 to June 2018. Those detected with abnormal biotinidase activity based on semi-quantitative assays underwent confirmatory serum tests. The biotinidase gene was sequenced in all confirmed cases. Results The combined incidence of partial and profound biotinidase deficiency was estimated at 1:13,909 live births (95% confidence limit 1:11,235–1:17,217), much higher than the incidence rates reported in other populations worldwide. The most frequent biotinidase gene variants were p.D444H (allele frequency, 0.016), haplotype c.1330G>C;c.511G>A (p.D444H;A171T), p.D543E, c.310-15delT (intronic), p.V199M, and p.H485Q. Together these accounted for 74.6% of the alleles analysed. Conclusion Newborn screening for biotinidase deficiency, which revealed a higher incidence in Minas Gerais, is feasible and plays a critical role in the early identification of affected neonates and prevention of symptoms and irreversible sequelae. Biotinidase gene sequencing is a useful tool to confirm the diagnosis, and also provides valuable information about genetic variability among different populations.