bluuebunny/crossref_metadata_2025_split huggingface dataset:
Circadian rhythms in bipolar disorder patient-derived neurons predict lithium response
Authors: Mishra Himanshu K. , Ying Noelle M. , Luis Angelica , Wei Heather , Nguyen Metta , Nakhla Timothy , Vandenburgh Sara , Alda Martin , Berrettini Wade H. , Brennand Kristen J. , Calabrese Joseph R. , Coryell William H. , Frye Mark A. , Gage Fred H. , Gershon Elliot S. , McInnis Melvin G. , Nievergelt Caroline M. , Nurnberger John I. , Shilling Paul D. , Oedegaard Ketil J. , Zandi Peter P. ,   The Pharmacogenomics of Bipolar Disorder Study, Kelsoe John R. , Welsh David K , McCarthy Michael J. 
Published: December 2020

AbstractBipolar disorder (BD) is a neuropsychiatric disorder with genetic risk factors defined by recurrent episodes of mania/hypomania, depression and circadian rhythm abnormalities. While lithium is an effective drug for BD, 30-40% of patients fail to respond adequately to treatment. Previous work has demonstrated that lithium affects the expression of “clock genes” and that lithium responders (Li-R) can be distinguished from non-responders (Li-NR) by differences in circadian rhythms. However, rhythm abnormalities in BD have not been evaluated in neurons and it is unknown if neuronal rhythms differ between Li-R and Li-NR. We used induced pluripotent stem cells (iPSCs) to culture neuronal precursor cells (NPC) and glutamatergic neurons from BD patients and controls. We identified strong circadian rhythms inPer2-lucexpression in NPCs and neurons from controls and Li-R. NPC rhythms in Li-R had a shorter circadian period. Li-NR rhythms were low-amplitude and profoundly weakened. In NPCs and neurons, expression ofPER2was higher in both BD groups compared to controls. In neurons, PER2 protein expression was higher in BD than controls, especially in Li-NR samples. In single cells, NPC and neuron rhythms in both BD groups were desynchronized compared to controls. Lithium lengthened period in Li-R and control neurons but failed to alter rhythms in Li-NR. In contrast, temperature entrainment increased amplitude across all groups, and partly restored rhythms in Li-NR neurons. We conclude that neuronal circadian rhythm abnormalities are present in BD and most pronounced in Li-NR. Rhythm deficits in BD may be partly reversible through stimulation of entrainment pathways.
Whole Genome Sequencing-based Characterization of Human Genome Variation and Mutation Burden in Botswana
Authors: Thami Prisca K. , Choga Wonderful T. , Mulisa Delesa D. , Dandara Collet , Shevchenko Andrey K. , Leteane Melvin M. , Novitsky Vlad , O’Brien Stephen J. , Essex Myron , Gaseitsiwe Simani , Chimusa Emile R. 
Published: December 2020

ABSTRACTThe study of human genome variations can contribute towards understanding population diversity and the genetic aetiology of health-related traits. We sought to characterise human genomic variations of Botswana in order to assess diversity and elucidate mutation burden in the population using whole genome sequencing. Whole genome sequences of 390 unrelated individuals from Botswana were available for computational analysis. The sequences were mapped to the human reference genome GRCh38. Population joint variant calling was performed using Genome Analysis Tool Kit (GATK) and BCFTools. Variant characterisation was achieved by annotating the variants with a suite of databases in ANNOVAR and snpEFF. The genomic architecture of Botswana was delineated through principal component analysis, structure analysis and FST. We identified a total of 27.7 million unique variants. Variant prioritisation revealed 24 damaging variants with the most damaging variants beingACTRT2rs3795263,HOXD12rs200302685,ABCB5rs111647033,ATP8B4rs77004004 andABCC12rs113496237. We observed admixture of the Khoe-San, Niger-Congo and European ancestries in the population of Botswana, however population substructure was not observed. This exploration of whole genome sequences presents a comprehensive characterisation of human genomic variations in the population of Botswana and their potential in contributing to a deeper understanding of population diversity and health in Africa and the African diaspora.
Analysis of Amino Acid Variants in Malignant Melanoma Cells Resistant to BRAF inhibition
Authors: Schmitt Marisa , Sinnberg Tobias , Bratl Katrin , Zittlau Katharina , Garbe Claus , Macek Boris , Nalpas Nicolas C. 
Published: December 2020

AbstractAnalysis of patient-specific nucleotide variants is a cornerstone of personalised medicine. Although only 2% of the genomic sequence is protein-coding, mutations occurring in these regions have the potential to influence protein structure and may have severe impact on disease aetiology. Of special importance are variants that affect modifiable amino acid residues, as protein modifications involved in signal transduction networks cannot be analysed by genomics. Proteogenomics enables analysis of proteomes in context of patient- or tissue-specific non-synonymous nucleotide variants. Here, we developed a proteogenomics workflow and applied it to study resistance to serine/threonine-protein kinase B-raf (BRAF) inhibitor (BRAFi) vemurafenib in malignant melanoma cell line A375. This approach resulted in high identification and quantification of non-synonymous nucleotide variants and (phospho)proteins. We integrated multi-omic datasets to reconstruct the perturbed signalling networks associated with BRAFi resistance and to predict drug therapies with the potential to disrupt BRAFi resistance mechanism in A375 cells. Notably, we showed that aurora kinase A (AURKA) inhibition is effective and specific against BRAFi resistant A375 cells. Furthermore, we investigated nucleotide variants that interfere with protein post-translational modification (PTM) status and potentially influence cell signalling. Mass spectrometry (MS) measurements confirmed variant-driven PTM changes in 12 proteins; among them was the runt-related transcription factor 1 (RUNX1) displaying a variant on a known phosphorylation site S(Ph)276L. We confirmed the loss of phosphorylation site by MS and demonstrated the impact of this variant on RUNX1 interactome.
A novel family of nonribosomal peptides modulate collective behavior inPseudovibriobacteria isolated from marine sponges
Authors: Ióca Laura P. , Dai Yitao , Kunakom Sylvia , Diaz-Espinosa Jennifer , Krunic Aleksej , Crnkovic Camila M. , Orjala Jimmy , Sanchez Laura M. , Ferreira Antonio G. , Berlinck Roberto G. S. , Eustáquio Alessandra S. 
Published: December 2020

AbstractCollective behavior is a common feature of life. Although swarming motility and biofilms are opposed collective behaviors, both contribute to bacterial survival and host colonization. We have identified a link between motility/biofilms and a nonribosomal peptide synthetase-polyketide synthase gene cluster family (ppp) conserved inPseudovibrioandPseudomonasProteobacteria known to interact with diverse eukaryotes. After developing reverse genetics forPseudovibrio, we discovered two pseudovibriamide families, heptapeptides with a reversal in chain polarity via an ureido linkage1-6and related nonadepsipeptides7-12. Imaging mass spectrometry showed that1was excreted whereas7was colony-associated. Deletion ofpppAabolished production of1-12leading to reduced motility and increased biofilm production.pppDmutants that produced only1-6showed motility comparable to the wild-type and reduced biofilm formation, indicating that the excreted heptapeptides play a role in promoting motility. In contrast to lipopeptides widely known to affect swarming and biofilms, pseudovibriamides are not surfactants. Our results expand current knowledge on metabolites mediating bacterial collective behavior. Moreover, the establishment of reverse genetics will enable future exploration of the ecological and biotechnological potential ofPseudovibriobacteria which have been proposed to contribute to marine sponge health.SignificanceBacteria contribute to health and disease of plants and animals. Specialized metabolites produced by bacteria are important in mediating their behavior and the colonization of their hosts. We have identified a conserved gene cluster family inPseudovibrioandPseudomonasbacteria known to colonize marine animals and terrestrial plants, respectively. UsingPseudovibrioas a model, we show the encoded metabolites, which we termed pseudovibriamides, promote motility and decrease biofilms. In contrast to lipopeptides widely known to affect motility/biofilms, pseudovibriamides are not surfactants, but instead are linear peptides with a reversal in chain polarity. The discovery of pseudovibriamides expands current knowledge of bacteria collective behavior. The establishment of reverse genetics will enable exploration of the ecological and biotechnological potential ofPseudovibriobacteria.ClassificationBiological Sciences, Microbiology
The core of business ethics
Authors: Hasnas John 
Published: December 2020

AbstractMuch of the focus on business ethics literature is on complex questions of corporate social responsibility. Yet, the heart of business ethics consists in a set of fundamental moral principles that are inherent in the activity of doing business in a market. These principles transcend differences in nationality, culture, and religion and supply the building blocks on which the more complex analyses can be based. This set of principles, which constitute the core of business ethics, provides business people with a code of conduct that is the analog of attorneys’ Canon of Ethics and physicians’ Code of Medical Ethics.
Use of random pattern skin flaps for wound closure in two horses
Authors: Jansson J. , Knottenbelt D. , Hennessy S. 
Published: December 2020

SummaryA 9‐year‐old Thoroughbred broodmare presented with a mass rostral to the medial canthus of the left eye. The mass was removed under general anaesthesia and the wound bed infiltrated with carboplatin emulsion before partially closing using a Z‐plasty. The mass recurred and subsequently was resected twice. It has not recurred 68 weeks post‐treatment. The second case describes removal of a granulomatous mass from the metatarsus of a yearling Thoroughbred colt. Skin expanders and a rotational flap were used to allow tension‐free closure. This required two separate surgeries to firstly insert the skin expanders and secondly to remove the mass, the expanders and to close the defect. The wound healed with good cosmesis. There have been few reports on the use of skin flaps in equine reconstructive surgery in the last 30 years. This report details two cases of wound closure where skin flaps were used to achieve primary intention wound healing.
A reduced panel of eight genes (ATM, SF3B1, NOTCH1, BIRC3, XPO1, MYD88, TNFAIP3, and TP53) as an estimator of the tumor mutational burden in chronic lymphocytic leukemia
Authors: Chauzeix Jasmine , Pastoret Cédric , Donaty Lucie , Gachard Nathalie , Fest Thierry , Feuillard Jean , Rizzo David 
Published: December 2020

AbstractIntroductionMutational complexity or tumor mutational burden (TMB) influences the course of chronic lymphocytic leukemia (CLL). However, this information is not routinely used because TMB is usually obtained from whole genome or exome, or from large gene panel high‐throughput sequencing.MethodsHere, we used the C‐Harrel concordance index to determine the minimum panel of genes for which mutations predict treatment‐free survival (TFS) as well as large resequencing panels.ResultsAn eight gene estimator was defined encompassing ATM, SF3B1, NOTCH1, BIRC3, XPO1, MYD88, TNFAIP3, and TP53. TMB estimated from either a large panel of genes or the eight gene estimator was increased in treated patients or in those with a short TFS (<2 years), unmutated IGHV gene or with an unfavorable karyotype. Being an independent prognostic parameter, any mutation in the eight gene estimator predicted a shorter TFS better than Binet stage and IGHV mutational status among patients with an apparently non‐progressive disease (TFS >6 months). Strikingly, the eight gene estimator was also highly informative for patients with Binet stage A CLL or with a good prognosis karyotype.ConclusionThese results suggest that the eight gene estimator, that is easily achievable by high‐throughput resequencing, brings robust and valuable information that predicts evolution of untreated patients at diagnosis better than any other parameter.
Taking a long view: Investor trading horizon and earnings management strategy
Authors: Jang Yeejin , Lee Kyung Yun (Kailey) 
Published: December 2020

AbstractThis paper studies how the investment horizon of institutional investors affects firms' earnings management strategy in terms of trade‐off decisions between accrual management and operational adjustment. We find that when overall earnings management motives are held fixed, firms in which long‐term investors hold large stakes are more likely to manage earnings by adjusting operational decisions than by manipulating accruals. The preference for real earnings management is more pronounced when long‐term investors face performance pressures and when they have a strong influence on managers. We further document that real earnings management helps smooth earnings, and the future adverse consequences of operational adjustment are relatively less severe for firms with a greater proportion of long‐term investors than for those with more short‐term investors. Our findings are robust to the endogenous choice of ownership structure. Overall, the evidence suggests that firms choose earnings management methods to meet the earnings expectations of institutional investors, who have different earnings target windows.
Effectiveness of lip repositioning surgeries in the treatment of excessive gingival display: A systematic review and meta‐analysis
Authors: dos Santos‐Pereira Silvio Antônio , Cicareli Álvaro José , Idalgo Fábio Alarcon , Nunes Alexandre Gomes , Kassis Elias Naim , Castanha Henriques José Fernando , Bellini‐Pereira Silvio Augusto 
Published: December 2020

AbstractTo synthesize the available evidence regarding lip repositioning surgery (LRS) and quantify the short‐ and long‐term reduction in excessive gingival display (EGD) with the procedure. Additionally, evaluate the effect of myotomy on the results. Seven electronic databases were searched up to May 2020 by two independent reviewers. Studies evaluating the exclusive use of LRS to treat EGD were included. After risk of bias assessment, the data were quantitatively evaluated with random‐effects meta‐analysis. The initial database search yielded 368 studies, of which 16 were selected for full‐text review. Finally, eight studies were included. The random effects model exhibited an EGD reduction of 2.87 mm (95% CI: 1.91–3.82) after 3 months of LRS. These results decreased after 6 months (2.71 mm; 95% CI: 1.95–3.47) and 12 months (2.10 mm; 95% CI: 1.48–2.72). Meta‐analysis comparing the performance of myotomy showed greater EGD reduction at 6 months than without myotomy (P < 0.02). LRS is an effective approach for treating EGD, and it has satisfactory results up to 6 months. After this period, the effectiveness appears to progressively decrease over time indicating substantial relapse at 12 months. Myotomy seems a suitable alternative to increase the stability of LRS. Lip repositioning surgery is an effective procedure to improve smile esthetics in the short‐term (up to 6 months). After this period, the efficacy of LRS seems to decrease progressively, and an approximately 25% relapse may be expected after 12 months. Clinicians should combine the procedure with other approaches, such as plastic periodontal surgeries, restorative procedures, or botulin toxin injections for more predictable and stable outcomes.
Raynaud's phenomenon as a presenting manifestation of ovarian cancer: A case report
Authors: Matanes Emad , Boulus Sari , Lauterbach Roy , Matanis Jawad , Reiss Ari , Amit Amnon 
Published: December 2020

AbstractRaynaud's phenomenon (RP) is characterized by episodes of vasospasm affecting the hands and feet. Paraneoplastic RP, as a single presenting symptom is rarely seen in cases of ovarian cancer (OC), and thus may lead to misdiagnosis. We present a case of paraneoplastic RP in a patient with high‐grade serous OC. A 66‐year‐old female presented with dyspnea and bilateral peripheral cyanosis involving her fingers. CA125 was elevated (423 U/mL). CT revealed a pleural effusion on the left side, suspicious omental lesions and ascites. Omental biopsy and pleural cytology demonstrated high‐grade serous OC. Neoadjuvant chemotherapy (carboplatin/paclitaxel) resulted in objective improvement in finger ischemia and complete regression of vasospastic features. However, the patient's disease was refractory to post‐surgical treatment and eventually she deceased of multiple organ failure. To conclude, RP may be a presenting symptom of OC. It is important to determine the underlying disease and develop an effective treatment strategy.
Tax treaties worldwide: Estimating elasticities and revenue foregone
Authors: Janský Petr , Láznička Jan , Palanský Miroslav 
Published: December 2020

AbstractWhile researchers agree that dividend and interest payments respond to tax treaties, evidence of the magnitude of this response remains scarce. We combine data from the International Bureau of Fiscal Documentation and the International Monetary Fund in a set of 65,000 annual country‐pair observations for the 2009–2016 period. We estimate dividend flows to be highly elastic in a cross‐country regression and arrive at somewhat lower and less robust estimates for interest income. While our revenue estimates are lower than static estimates which do not reflect elasticities, we show that for some countries the revenue foregone remains non‐negligible.
Fiscal competition for foreign direct investment with knowledge spillovers and trade costs
Authors: Ferrett Ben , Gravino Daniel 
Published: December 2020

AbstractWe develop a model of fiscal competition for foreign direct investment and show that the decision of multinational firms to locate in the proximity of indigenous firms—which can be thought of as agglomeration—may be the result of the provision of government incentives that aim to capitalise on the potential for knowledge spillovers to indigenous industry. Somewhat different but complementary to existing literature, we also show that fiscal competition may increase the welfare of both winning and losing countries in the auction for the multinational firm when it leads to the relocation of multinationals away from countries that do not have the potential to benefit from knowledge spillovers to countries that do. As trade costs fall and the potential for knowledge spillovers increases, both outcomes become more likely in equilibrium.
Companion-animal-inclusive domestic violence practice: Implications for service delivery and social work
Authors: Taylor Nik , Fraser Heather , Riggs Damien W. 
Published: December 2020

INTRODUCTION: Based on an understanding of links between human- and animal-directed domestic violence, this article: 1) argues for companion-animal inclusive domestic violence service delivery; and 2) reflects on the challenges this offers to social work and the human services.APPROACH: We start by considering the importance of companion animals in many people’s lives and then offer an overview of material on “the link” between human- and animal-directed violence, specifically as it pertains to domestic violence.CONCLUSIONS: Implications for service design and provision are discussed. We conclude with brief comments about the importance of centring animals in future considerations of human– animal violence links and outline how this offers an opportunity to challenge and re-think the humanist foundations on which traditional social work is built.
“It’s about the most needy children”: A Foucauldian analysis of school social workers’ responses to need in post-earthquake Canterbury
Authors: Tudor Raewyn 
Published: December 2020

INTRODUCTION: After the 2011 Canterbury earthquake, the provision of school social work was extended into a larger number of schools in the greater Christchurch region to support discussions of their practice priorities and responses in post-earthquake schools.FINDINGS: Two main interpretations of need are reflected in the school social workers’ accounts of their work with children and families. Firstly, hardship-focused need, which represented children as adversely influenced by their home circumstances; the interventions were primarily with parents. These families were mainly from schools in low socioeconomic areas. Secondly, anxiety-based need, a newer practice response, which emphasised children who were considered particularly susceptible to the impacts of the disaster event. This article considers how these practitioners conceptualised and responded to the needs of the children and their families in this context.METHOD: A qualitative study examining recovery policy and school social work practice following the earthquakes including 12 semi-structured interviews with school social workers. This article provides a Foucauldian analysis of the social worker participants’ perspectives on emotional and psychological issues for children, particularly those from middle-class families; the main interventions were direct therapeutic work with children themselves. Embedded within these practice accounts are moments in which the social workers contested the predominant, individualising conceptualisations of need to enable more open-ended, negotiable, interconnected relationships in post-earthquake schools.IMPLICATIONS: In the aftermath of disasters, school social workers can reflect on their preferred practice responses and institutional influences in schools to offer children and families opportunities to reject the prevalent norms of risk and vulnerability.