bluuebunny/crossref_metadata_2025_split huggingface dataset:
Frequent upregulation of G9a promotes RelB-dependent proliferation and survival in multiple myeloma
Authors: Zhang Xi Yun , Rajagopalan Deepa , Chung Tae-Hoon , Hooi Lissa , Toh Tan Boon , Tian Johann Shane , Rashid Masturah Bte Mohd Abdul , Sahib Noor Rashidha Bte Meera , Gu Mengjie , Lim Jhin Jieh , Wang Wilson , Chng Wee Joo , Jha Sudhakar , Chow Edward Kai-Hua 
Published: May 2020

Abstract
Background
Multiple myeloma is an incurable hematological malignancy characterized by a heterogeneous genetic and epigenetic landscape. Although a number of genetic aberrations associated with myeloma pathogenesis, progression and prognosis have been well characterized, the role of many epigenetic aberrations in multiple myeloma remain elusive. G9a, a histone methyltransferase, has been found to promote disease progression, proliferation and metastasis via diverse mechanisms in several cancers. A role for G9a in multiple myeloma, however, has not been previously explored.

Methods
Expression levels of G9a/EHMT2 of multiple myeloma cell lines and control cells Peripheral Blood Mononuclear Cells (PBMCs) were analyzed. Correlation of G9a expression and overall survival of multiple myeloma patients were analyzed using patient sample database. To further study the function of G9a in multiple myeloma, G9a depleted multiple myeloma cells were built by lentiviral transduction, of which proliferation, colony formation assays as well as tumorigenesis were measured. RNA-seq of G9a depleted multiple myeloma with controls were performed to explore the downstream mechanism of G9a regulation in multiple myeloma.

Results
G9a is upregulated in a range of multiple myeloma cell lines. G9a expression portends poorer survival outcomes in a cohort of multiple myeloma patients. Depletion of G9a inhibited proliferation and tumorigenesis in multiple myeloma. RelB was significantly downregulated by G9a depletion or small molecule inhibition of G9a/GLP inhibitor UNC0642, inducing transcription of proapoptotic genes Bim and BMF. Rescuing RelB eliminated the inhibition in proliferation and tumorigenesis by G9a depletion.

Conclusions
In this study, we demonstrated that G9a is upregulated in most multiple myeloma cell lines. Furthermore, G9a loss-of-function analysis provided evidence that G9a contributes to multiple myeloma cell survival and proliferation. This study found that G9a interacts with NF-κB pathway as a key regulator of RelB in multiple myeloma and regulates RelB-dependent multiple myeloma survival. G9a therefore is a promising therapeutic target for multiple myeloma.
No evidence for Wolbachia as a nutritional co-obligate endosymbiont in the aphid Pentalonia nigronervosa
Authors: Manzano-Marín Alejandro 
Published: May 2020

AbstractObligate symbiotic associations are present in a wide variety of animals with a nutrient-restricted diet. Aphids (hemiptera: Aphididae) almost-universally host Buchnera aphidicola bacteria in specialised organs (called bacteriomes). These bacteria supply the aphid with essential nutrients lacking from their diet (i.e. essential amino acids and some B vitamins). Some aphid lineages, such as species from the Lacninae subfamily, have evolved co-obligate associations with secondary endosymbionts, deriving from a loss of biotin- and riboflavin-biosynthetic genes. In this study, I re-analyse previously published sequencing data from the banana aphid Pentalonia nigronervosa. I show that the metabolic inference results from De Clerck et al. (Microbiome 3:63, 2015) are incorrect and possibly arise from the use of inadequate methods. Additionally, I discuss how the seemingly biased interpretation of their antibiotic treatment analyses together with an incorrect genome-based metabolic inference resulted in the erroneous suggestion “that a co-obligatory symbiosis between B. aphidicola and Wolbachia occurs in the banana aphid”.
Relationship between circulating miR-132 and non-alcoholic fatty liver disease in a Chinese population
Authors: Zong Yicen , Yan Jing , Jin Li , Xu Bo , He Zhen , Zhang Rong , Hu Cheng , Jia Weiping 
Published: May 2020

AbstractBackgroundNon-invasive diagnostic markers are of great importance for early screening nonalcoholic fatty liver disease (NAFLD). MicroRNAs (miRNAs) play significant roles in many metabolic disease, including NAFLD. Therefore, this study focusd on a Chinese population to explore the possible correlation between circulating miR-132 and NAFLD.ResultsSerum miR-132 was positively associated with NAFLD in non-type 2 diabetes mellitus (T2DM) groups by logistic regression (OR = 3.082 [1.057, 8.988],P = 0.039) after adjusting age, sex, and body mass index (BMI). Additionally, in non-T2DM subgroup, after adjusting age, sex, bmi, serum miR-132 was significantly associated with ALT (β ± SE = 0.005 ± 0.002,P = 0.018), TG (β ± SE = 0.072 ± 0.029,P = 0.015), FPG (β ± SE = 0.123 ± 0.058,P = 0.036), γ-GT (β ± SE = 0.002 ± 0.001,P = 0.047), apoE (β ± SE = 0.038 ± 0.002,P = 0.017) .ConclusionsSerum miR-132 was found to be associated with NAFLD risk in a Chinese cross-section study. This finding provides a prospective research direction for early screening and diagnosing NAFLD.
Genomic Profiling of Smoldering Multiple Myeloma Identifies Patients at a High Risk of Disease Progression
Authors: Bustoros Mark , Sklavenitis-Pistofidis Romanos , Park Jihye , Redd Robert , Zhitomirsky Benny , Dunford Andrew J. , Salem Karma , Tai Yu-Tzu , Anand Shankara , Mouhieddine Tarek H. , Chavda Selina J. , Boehner Cody , Elagina Liudmila , Neuse Carl Jannes , Cha Justin , Rahmat Mahshid , Taylor-Weiner Amaro , Van Allen Eliezer , Kumar Shaji , Kastritis Efstathis , Leshchiner Ignaty , Morgan Elizabeth A. , Laubach Jacob , Casneuf Tineke , Richardson Paul , Munshi Nikhil C. , Anderson Kenneth C. , Trippa Lorenzo , Aguet François , Stewart Chip , Dimopoulos Meletios-Athanasios , Yong Kwee , Bergsagel P. Leif , Manier Salomon , Getz Gad , Ghobrial Irene M. 
Published: May 2020

PURPOSE Smoldering multiple myeloma (SMM) is a precursor condition of multiple myeloma (MM) with a 10% annual risk of progression. Various prognostic models exist for risk stratification; however, those are based on solely clinical metrics. The discovery of genomic alterations that underlie disease progression to MM could improve current risk models. METHODS We used next-generation sequencing to study 214 patients with SMM. We performed whole-exome sequencing on 166 tumors, including 5 with serial samples, and deep targeted sequencing on 48 tumors. RESULTS We observed that most of the genetic alterations necessary for progression have already been acquired by the diagnosis of SMM. Particularly, we found that alterations of the mitogen-activated protein kinase pathway ( KRAS and NRAS single nucleotide variants [SNVs]), the DNA repair pathway (deletion 17p, TP53, and ATM SNVs), and MYC (translocations or copy number variations) were all independent risk factors of progression after accounting for clinical risk staging. We validated these findings in an external SMM cohort by showing that patients who have any of these three features have a higher risk of progressing to MM. Moreover, APOBEC associated mutations were enriched in patients who progressed and were associated with a shorter time to progression in our cohort. CONCLUSION SMM is a genetically mature entity whereby most driver genetic alterations have already occurred, which suggests the existence of a right-skewed model of genetic evolution from monoclonal gammopathy of undetermined significance to MM. We identified and externally validated genomic predictors of progression that could distinguish patients at high risk of progression to MM and, thus, improve on the precision of current clinical models.
The effects of a temporal processing-based auditory training program on the auditory skills of elderly users of hearing aids: a study protocol for a randomized clinical trial
Authors: Rahbar Nariman , Sattari Karim , Ahadi Mohsen , Haghani Hamid 
Published: May 2020

Background: One of the most important effects of age-related declines in neural processing speed is the impairment of temporal resolution, which leads to difficulty hearing in noisy environments. Since the central auditory system is highly plastic, by designing and implementing a temporal processing-based auditory training program, we can help the elderly improve their listening skills and speech understanding in noisy environments.Methods:In the first phase of this research, based on the theoretical framework of temporal processing, an auditory training solution was developed as a software program. In the second phase, which will be described in the present study, the effects of the designed program on the listening skills of the elderly users of hearing aids (age: 60-75 years) will be studied in the control and intervention groups. In the intervention group, the auditory training program will be implemented for three months (36 sessions), and the results of central tests (GIN, DPT, QuickSIN) and the electrophysiological speech-ABR test will be compared in both groups before, immediately and one month after the intervention.Discussion: Since temporal processing is not sufficient in auditory training programs for the elderly with hearing impairments, implementation of a temporal processing-based auditory training program can reduce hearing problems in noisy environments among elderly users of hearing aids.Trial registration:This study was registered as a clinical trial in the Iranian Registry of Clinical Trials (IRCT20190921044838N1) on December 25, 2019.
Glycoalkaloids in commercial potato varieties traded in Nairobi, Kenya
Authors: Musita Consolata Nolega , Omayio Duke Gekonge , Abong' George Ooko , Okoth Michael Wandayi 
Published: May 2020

Background: Glycoalkaloids are naturally occurring toxins in potatoes which, at high levels, pose food safety concerns to consumers. Their concentrations in potatoes are dependent on postharvest handling, variety and stress factors tubers are exposed to. Limited information, however, exists on levels of glycoalkaloids in commercially traded potato tubers in Kenya. The current study sought to determine the glycoalkaloid levels in potatoes traded in Nairobi, Kenya. Methods: Three potato varieties, Shangi, Dutch Robjin and Royal sold in open-air markets and supermarkets were randomly sampled and their glycoalkaloid levels determined by high-performance liquid chromatography. Results: The levels varied significantly (p<0.05). The Shangi variety had the highest glycoalkaloids with a mean of 410.35 mg kg-1 dry weight with samples from supermarkets having the highest levels (550.8 mg kg-1). The same variety from open air markets averaged 382.26 mg kg-1 dry weight compared to the Dutch Robjin (129.2 mg kg-1 dry weight) and Royal variety (98.2 mg kg-1 dry weight) which had the least levels of glycoalkaloids. Conclusions: The levels in sampled tubers did not exceed the recommended levels of 1000 mg/kg on dry weight basis and, therefore, consumption of these potatoes would not raise safety concerns. There is, however, a need to ensure that marketing of tubers is carried out under conditions that minimize occurrence of glycoalkaloids, especially for the Shangi variety, which is the most common in the markets but had relatively high levels of these toxins. There is also a need to educate marketers on the need for proper storage and handling of potatoes during marketing to avoid risk of accumulation of glycoalkaloids.
Exploration in Teams and the Encouragement Effect: Theory and Experimental Evidence
Authors: von Essen Emma , Huysentruyt Marieke , Miettinen Topi 
Published: May 2020

This paper analyzes a two-person, two-stage model of sequential exploration where both information and payoff externalities exist and tests the derived hypotheses in the laboratory. We theoretically show that, even when agents are self-interested and perfectly rational, the information externality induces an encouragement effect: a positive effect of first player exploration on the optimality of the second player exploring as well. When agents have other-regarding preferences and imperfectly optimize, the encouragement effect is strongest. The explorative nature of the game raises the expected surplus compared with a payoff equivalent public goods game. We empirically confirm our main theoretical predictions using a novel experimental paradigm. Our findings are relevant for motivating and managing groups and teams innovating not only for private but also and especially so, for public goods.This paper was accepted by John List, behavioral economics.
Implicações da Gestalt-terapia Frente às Relações de Hiperconsumo
Authors: Alegria Carla Machado 
Published: May 2020

A hipermodernidade, com suas bases culturais fundamentadas no individualismo e nas relações de consumo, levou o homem a um completo esgotamento frente às expectativas de felicidade a ser obtida por meio da conquista de melhores desempenhos em vários aspectos da existência e em aquisições materiais. Uma vez que o indivíduo está constantemente exposto às consequências do modus vivendi do hiperconsumo, qual seja, o caráter transitório do sucesso que provoca o sentimento de fracasso, são observadas sequelas emocionais que podem se desdobrar em fenômenos psicopatológicos contemporâneos, sendo alguns destes destacados no artigo. O objetivo deste trabalho é apontar como a força do imperativo do sucesso pode intensificar sentimentos como humilhação, vergonha e inveja, assim como sugerir a Gestalt-terapia como oportunidade de libertação da opressora ideologia da superação de si, por ser, pelo encontro dialógico, um instrumento na sustentação da dignidade do sujeito diante das desconfirmações a que é constantemente submetido.
Biomusicalidade, Experiência e Awareness Coletiva: Gestalt-Terapia e Musicoterapia no Cuidado de Pais e Bebês
Authors: Peixoto Paulo-de-Tarso De Castro 
Published: May 2020

O artigo apresenta caminhos sobre a produção do cuidado para pais e bebês. Inicialmente é apresentado o conceito de ‘biomusicalidade', trazendo em cena a visão da vida tecida em contrapontos, a partir dos signos-sinais afetivos advindos das relações. As perspectivas da Gestalt-Terapia, da Musicoterapia e das Filosofias da Imanência sustentam as experiências de produção do cuidado para os pais e bebês. Problematiza-se a questão da produção de novas temporalidades nas relações entre os pais dirigida à produção do cuidado onde a subjetividade dos filhos seja ‘afetada' por campos de experiências vitais. Experiências movidas pela potência do desejo da descoberta, da busca pela novidade, do desejo de conexão com algo do ambiente que possa nutrir. Experiências da potência do devir-criança que habita os adultos e que pode ser despertada pelos campos de afetação do espaço clínico. O artigo propõe o desenvolvimento de uma Scientia Patibilis Natura, como uma Ciência da Alma Sensível. Ciência aliançada a uma ‘fenomenologia biomusical' que orienta e excita as consciências sensíveis dos pais para a produção de uma consciência sensível mutual, uma awareness coletiva. Experiências produtoras de um espaço clínico excitante, espaço da relação, espaço do sagrado, espaço da musicalidade da vida, espaço biomusical.
As Contribuições da Psicologia aos Ideais da Liga Brasileira de Higiene Mental: Algumas Reflexões
Authors: Borges Roselania Francisconi 
Published: May 2020

A psicologia científica é um produto histórico configurado por uma diversidade teórica e metodológica que, em solo brasileiro, foi fortemente constituída no final do século XIX e início do século XX. Tendo em vista esta diversidade, este estudo faz um recorte e trata da parceria entre a Psicologia e a Liga Brasileira de Higiene Mental (LBHM), no que tange às aferições das diferenças individuais. O movimento higienista, materializado pela LBHM, exerceu forte influência sobre as práticas psicológicas as quais serviram de sustentação científica para a implantação de políticas públicas visando um padrão de normalidade, via seleção dos considerados capazes e incapazes, tanto para fatores relacionados a padrões de conduta e de comportamento, quanto para fatores relacionados a aprendizagem de conteúdos acadêmicos. Atualmente, em meio a inúmeras tentativas de implantação de pautas conservadoras nas políticas públicas, grande parte dos profissionais da Psicologia busca compreender em que os saberes psicológicos podem contribuir para ampliar avanços e evitar retrocessos. Exercitar a competência para a reflexão que a ciência psicológica proporciona pode ser uma alternativa para suplantar a histórica busca de um dado padrão de normalidade. Após mais de um século, esta ainda parece ser uma tarefa urgente e necessária para a Psicologia.
Captação e subversão de práticas intersemióticas: uma análise discursiva no contexto político brasileiro
Authors: Sampaio de Almeida Fabio , Moraes Rego de Souza Alice , Giorgi Maria Cristina 
Published: May 2020

Neste artigo, buscando articular contribuições da Análise do Discurso enunciativa, às propostas de Bakhtin quanto ao dialogismo e aos gêneros de discurso, objetivamos discutir os processos de captação e subversão (MAINGUENEAU, 1997), no contexto da internet, de um gênero do discurso intersemiótico para produzir um posicionamento outro, marcado pelo embate entre diferentes formações discursivas. À luz desses referenciais teóricos, empreendemos uma análise discursiva de uma capa da revista Exame, abordando a questão da reforma da previdência no Brasil – proposta pelo governo de Michel Temer em 2016 – e de uma paródia desse mesmo texto. Os resultados de análise possibilitam compreender que captação e subversão são parte de um mesmo processo e que, no âmbito de práticas intersemióticas na internet entre diferentes formações discursivas fazem parte do repertório da competência discursiva de uma comunidade que se posiciona contra discursos neoliberais. Por meio deste percurso pautado na perspectiva discursiva, esperamos colaborar, em termos teórico-analíticos, com pesquisas que se voltam para a análise de textos verbo-visuais oriundos da internet, propondo a reflexão sobre saberes produzidos em enunciados que circulam atualmente em nosso país sobre temas de natureza política.
Studi Pemanfaatan Produk Recovery Alum Dari Lumpur IPAM sebagai Koagulan pada Proses Koagulasi – Flokulasi
Authors: Oktaviani Serly 
Published: May 2020

Produksi Lumpur unit Clearator pada Instalasi Pengolahan Air Minum (IPAM cukup besar. Lumpur dari unit clearator ini masih mengadung alumunium cukup besar. Kandungan Al dalam lumpur ini dimungkinkan bisa dimanfaatkan kembali melalui proses recovery. Metode recovery dalam penelitian menggunakan proses asidifikasi, dengan menambahkan larutan asam sampai pH 1-3. Efektifitas Al hasil recovery diuji dengan menambahkan pada proses koagulasi flokulasi menggunakan air baku yang sama. Penelitian dilakukan dengan variasi pH, kecepatan dan waktu pengadukan. Variasi pH dilakukan pada pH 2, 3 dan 4 sedangkan kecepatan pengadukan pada 100 dan 120 rpm, dengan waktu masing – masing 30 dan 45 menit. Hasil penelitian proses recovery alum diperoleh kondisi terbaik pada pH 2, kecepatan pengadukan 100 rpm, dengan waktu pengadukan 45 menit, menghasilkan kadar alum sebesar 3,2912 mg Al/gram lumpur kering. Efektifitas Al recovery diuji pada proses koagulasi dan flokulasi dengan kombinasi Al recovery dan Tawas asli pada variasi kekeruhan air 13 NTU, 11NTU dan 10 NTU. Hasil penelitian terbaik pada kekeruhan air 11 NTU dengan kombinasi Tawas asli dan Al recovery 3:2 menghasilkan kekeruhan akhir 0,75 NTU. Analisis perbandingan biaya Al produk recovery, kombinasi dan Tawas asli berturut turut sebesar Rp 32500, Rp 13510, dan Rp 850. Proses recovery tidak layak untuk proses bisnis, namun layak untuk pengendalian pencemaran lingkungan.
Subtrochanteric femoral shortening for hip centre restoration in complex total hip arthroplasty with functional outcome
Authors: Oommen A. T. , Chandy V. J. , Jeyaraj Christo , Kandagaddala Madhavi , Hariharan T. D. , Arun Shankar A. , Poonnoose P. M. , Korula Ravi Jacob 
Published: May 2020

Aims Complex total hip arthroplasty (THA) with subtrochanteric shortening osteotomy is necessary in conditions other than developmental dysplasia of the hip (DDH) and septic arthritis sequelae with significant proximal femur migration. Our aim was to evaluate the hip centre restoration with THAs in these hips. Methods In all, 27 THAs in 25 patients requiring THA with femoral shortening between 2012 and 2019 were assessed. Bilateral shortening was required in two patients. Subtrochanteric shortening was required in 14 out of 27 hips (51.9%) with aetiology other than DDH or septic arthritis. Vertical centre of rotation (VCOR), horizontal centre of rotation, offset, and functional outcome was calculated. The mean followup was 24.4 months (5 to 92 months). Results The mean VCOR was 17.43 mm (9.5 to 27 mm) and horizontal centre of rotation (HCOR) was 24.79 mm (17.2 to 37.6 mm). Dislocation at three months following acetabulum reconstruction required femoral shortening for offset correction and hip centre restoration in one hip. Mean horizontal offset was 39.72 (32.7 to 48.2 mm) compared to 42.89 (26.7 to 50.6 mm) on the normal side. Mean Harris Hip Score (HHS) of 22.64 (14 to 35) improved to 79.43 (68 to 92). Mean pre-operative shortening was 3.95 cm (2 to 8 cm). Residual limb length discrepancy was 1.5 cm (0 to 2 cm). Sciatic neuropraxia in two patients recovered by six months, and femoral neuropraxia in one hip recovered by 12 months. Mean Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was 13.92 (9 to 19). Mean 12-item short form survey (SF-12) physical scores of 50.6 and mental of 60.12 were obtained. Conclusion THA with subtrochanteric shortening is valuable in complex hips with high dislocation. The restoration of the hip centre of rotation and offset is important in these hips. Level of evidence IV Femoral shortening useful in conditions other than DDH and septic sequelae. Restoration of hip centre combined with offset to be planned and ensured.
Benefits of the Educational Leadership Programme for Surgeons (ELPS)
Authors: Beard J , Gulati A 
Published: May 2020

The Educational Leadership Programme for Surgeons (ELPS) has been developed by The Royal College of Surgeons of England with the aim of helping senior surgeon educators to develop key leadership skills. The format combines the flexibility of online learning with two face-to-face days of interactive activities. Many key management and leadership principles are covered in the context of an educational environment. The two days are separated by a two-month period to encourage participants to develop their own action plan with a view to expanding their role and influence as surgeon educators. This article conveys the content of the ELPS programme in more detail and explains how it helped one of the participants to successfully achieve educational change at his hospital trust regarding induction and training. Creating and sustaining a learning culture in the NHS.