bluuebunny/crossref_metadata_2025_split huggingface dataset:
SLAMF3-Mediated Signaling via ERK Pathway Activation Promotes Aggressive Phenotypic Behaviors in Multiple Myeloma
Authors: Ishibashi Mariko , Takahashi Risa , Tsubota Asako , Sasaki Makoto , Handa Hiroshi , Imai Yoichi , Tanaka Norina , Tsukune Yutaka , Tanosaki Sakae , Ito Shigeki , Asayama Toshio , Sunakawa Mika , Kaito Yuta , Kuribayashi-Hamada Yasuko , Onodera Asaka , Moriya Keiichi , Komatsu Norio , Tanaka Junji , Odajima Takeshi , Sugimori Hiroki , Inokuchi Koiti , Tamura Hideto 
Published: January 2020

Abstract

The signaling lymphocytic activation molecule family 3 (SLAMF3) is a member of the immunoglobulin superfamily expressed on T, B, and natural killer cells and modulates the activation and cytotoxicity of these cells. SLAMF3 is also expressed on plasma cells from patients with multiple myeloma (MM), although its role in MM pathogenesis remains unclear. This study found that SLAMF3 is highly and constitutively expressed on MM cells regardless of disease stage and that SLAMF3 knockdown/knockout suppresses proliferative potential and increases drug-induced apoptosis with decreased levels of phosphorylated ERK protein in MM cells. SLAMF3-overexpressing MM cells promote aggressive myeloma behavior in comparison with cytoplasmic domain-truncated SLAMF3 (ΔSLAMF3) cells. SLAMF3 interacts directly with adaptor proteins SH2 domain-containing phosphatase 2 (SHP2) and growth factor receptor bound 2 (GRB2), which also interact with each other. SLAMF3 knockdown, knockout, ΔSLAMF3, and SHP2 inhibitor-treated MM cells decreased phosphorylated ERK protein levels. Finally, serum soluble SLAMF3 (sSLAMF3) levels were markedly increased in advanced MM. Patients with high levels of sSLAMF3 progressed to the advanced stage significantly more often and had shorter progression-free survival times than those with low levels. This study revealed that SLAMF3 molecules consistently expressed on MM cells transmit MAPK/ERK signals mediated via the complex of SHP2 and GRB2 by self-ligand interaction between MM cells and induce a high malignant potential in MM. Furthermore, high levels of serum sSLAMF3 may reflect MM disease progression and be a useful prognostic factor.

Implications:
SLAMF3 may be a new therapeutic target for immunotherapy and novel agents such as small-molecule inhibitors.
Type I Interferon Regulates a Coordinated Gene Network to Enhance Cytotoxic T Cell–Mediated Tumor Killing
Authors: Fan Jun-Bao , Miyauchi Sayuri , Xu Hui-Zhong , Liu Dan , Kim Leo J.Y. , Burkart Christoph , Cheng Hua , Arimoto Kei-ichiro , Yan Ming , Zhou Yu , Győrffy Balázs , Knobeloch Klaus-Peter , Rich Jeremy N. , Cang Hu , Fu Xiang-Dong , Zhang Dong-Er 
Published: January 2020

Abstract

Type I interferons (IFN), which activate many IFN-stimulated genes (ISG), are known to regulate tumorigenesis. However, little is known regarding how various ISGs coordinate with one another in developing antitumor effects. Here, we report that the ISG UBA7 is a tumor suppressor in breast cancer. UBA7 encodes an enzyme that catalyzes the covalent conjugation of the ubiquitin-like protein product of another ISG (ISG15) to cellular proteins in a process known as “ISGylation.” ISGylation of other ISGs, including STAT1 and STAT2, synergistically facilitates production of chemokine-receptor ligands to attract cytotoxic T cells. These gene-activation events are further linked to clustering and nuclear relocalization of STAT1/2 within IFN-induced promyelocytic leukemia (PML) bodies. Importantly, this coordinated ISG–ISGylation network plays a central role in suppressing murine breast cancer growth and metastasis, which parallels improved survival in patients with breast cancer. These findings reveal a cooperative IFN-inducible gene network in orchestrating a tumor-suppressive microenvironment.

Significance:
We report a highly cooperative ISG network, in which UBA7-mediated ISGylation facilitates clustering of transcription factors and activates an antitumor gene-expression program. These findings provide mechanistic insights into immune evasion in breast cancer associated with UBA7 loss, emphasizing the importance of a functional ISG–ISGylation network in tumor suppression.
This article is highlighted in the In This Issue feature, p. 327
Monocytic Subclones Confer Resistance to Venetoclax-Based Therapy in Patients with Acute Myeloid Leukemia
Authors: Pei Shanshan , Pollyea Daniel A. , Gustafson Annika , Stevens Brett M. , Minhajuddin Mohammad , Fu Rui , Riemondy Kent A. , Gillen Austin E. , Sheridan Ryan M. , Kim Jihye , Costello James C. , Amaya Maria L. , Inguva Anagha , Winters Amanda , Ye Haobin , Krug Anna , Jones Courtney L. , Adane Biniam , Khan Nabilah , Ponder Jessica , Schowinsky Jeffrey , Abbott Diana , Hammes Andrew , Myers Jason R. , Ashton John M. , Nemkov Travis , D'Alessandro Angelo , Gutman Jonathan A. , Ramsey Haley E. , Savona Michael R. , Smith Clayton A. , Jordan Craig T. 
Published: January 2020

Abstract

Venetoclax-based therapy can induce responses in approximately 70% of older previously untreated patients with acute myeloid leukemia (AML). However, up-front resistance as well as relapse following initial response demonstrates the need for a deeper understanding of resistance mechanisms. In the present study, we report that responses to venetoclax +azacitidine in patients with AML correlate closely with developmental stage, where phenotypically primitive AML is sensitive, but monocytic AML is more resistant. Mechanistically, resistant monocytic AML has a distinct transcriptomic profile, loses expression of venetoclax target BCL2, and relies on MCL1 to mediate oxidative phosphorylation and survival. This differential sensitivity drives a selective process in patients which favors the outgrowth of monocytic subpopulations at relapse. Based on these findings, we conclude that resistance to venetoclax + azacitidine can arise due to biological properties intrinsic to monocytic differentiation. We propose that optimal AML therapies should be designed so as to independently target AML subclones that may arise at differing stages of pathogenesis.

Significance:
Identifying characteristics of patients who respond poorly to venetoclax-based therapy and devising alternative therapeutic strategies for such patients are important topics in AML. We show that venetoclax resistance can arise due to intrinsic molecular/metabolic properties of monocytic AML cells and that such properties can potentially be targeted with alternative strategies.
Directing Traffic: How to Effectively Drive T Cells into Tumors
Authors: Anandappa Annabelle J. , Wu Catherine J. , Ott Patrick A. 
Published: January 2020

AbstractAlthough immune checkpoint inhibitors (ICI) have demonstrated clinical activity in multiple tumor types, the majority of patients do not respond to ICI monotherapy. Mounting evidence suggests that ICI-mediated clinical responses rely upon tumor infiltration by T cells that are able to recognize and kill cancer cells. Here, we review therapeutic modalities that have been shown to promote T-cell infiltration into human tumors in studies to date, and discuss emerging data guiding how these modalities can be sequenced in order to optimize T-cell effector function and memory T-cell generation, while minimizing overactivation and potential toxicity.Significance:The lack of preexisting T-cell inflammation in tumors is a major barrier to effective cancer immunity. A deep understanding of the mechanisms that prevent T cells from trafficking into the tumor in a given individual will be critical for tailoring immunotherapy combinations that can overcome resistance to ICI in patients with cancer.
Cryo-Electron Microscopy Structure of the αIIbβ3-Abciximab Complex
Authors: Nešić Dragana , Zhang Yixiao , Spasic Aleksandar , Li Jihong , Provasi Davide , Filizola Marta , Walz Thomas , Coller Barry S. 
Published: January 2020

Objective:
The αIIbβ3 antagonist antiplatelet drug abciximab is the chimeric antigen-binding fragment comprising the variable regions of murine monoclonal antibody 7E3 and the constant domains of human IgG1 and light chain κ. Previous mutagenesis studies suggested that abciximab binds to the β3 C177-C184 specificity-determining loop (SDL) and Trp129 on the adjacent β1-α1 helix. These studies could not, however, assess whether 7E3 or abciximab prevents fibrinogen binding by steric interference, disruption of either the αIIbβ3-binding pocket for fibrinogen or the β3 SDL (which is not part of the binding pocket but affects fibrinogen binding), or some combination of these effects. To address this gap, we used cryo-electron microscopy to determine the structure of the αIIbβ3-abciximab complex at 2.8 Å resolution.

Approach and Results:
The interacting surface of abciximab is comprised of residues from all 3 complementarity-determining regions of both the light and heavy chains, with high representation of aromatic residues. Binding is primarily to the β3 SDL and neighboring residues, the β1-α1 helix, and β3 residues Ser211, Val212 and Met335. Unexpectedly, the structure also indicated several interactions with αIIb. As judged by the cryo-electron microscopy model, molecular-dynamics simulations, and mutagenesis, the binding of abciximab does not appear to rely on the interaction with the αIIb residues and does not result in disruption of the fibrinogen-binding pocket; it does, however, compress and reduce the flexibility of the SDL.

Conclusions:
We deduce that abciximab prevents ligand binding by steric interference, with a potential contribution via displacement of the SDL and limitation of the flexibility of the SDL residues.
From Abramtsevo to Zakopane: Folk Art and National Ideals in Russia and Eastern Europe
Authors: Hilton Alison 
Published: January 2020

Abstract
Folk art revivals were incubators for modernist movements in painting, sculpture, architecture, applied arts, and performing arts. The upsurge of national sentiment in late Imperial Russia and official economic support of handicraft industries (known as kustar’) promoted the marketing of wood crafts and textiles made at Abramtsevo, Talashkino, and other centers in western Russia and Ukraine. Parallel developments drew upon both folk traditions and patriotic ideals in the central and eastern European countries that had suffered territorial encroachments by Russia, Prussia, and the Austro-Hungarian Empire. Artists’ groups and art colonies showed special respect for regional landscapes, peasant communities, and local artistic traditions. Their activities reflected nationalist ideologies, as well as practical, economic, and philanthropic concerns. The variety of circumstances and motivations sheds light on the phenomena of art colonies, new valuations of applied art forms, and the enduring importance of education in traditional crafts.
Revision of the genus Dziriblatta Chopard, 1936 (Blattodea, Ectobiidae, Ectobiinae). II. The species of the subgenera Pauciscleroblatta and Monoscleroblatta
Authors: BOHN HORST 
Published: January 2020

The present paper is a continuation of the revision of the genus Dziriblatta started with definition and description of the nine subgenera of the genus (Bohn 2019). In that first part of the revision usually only one species of each subgenus was described; the remaining species should be treated in following papers of which this contribution is the first dealing with the species of the subgenera Pauciscleroblatta (6 species) and Monoscleroblatta (4 species). Five species are new to science: Dziriblatta (Pauciscleroblatta) cyprica, spec. nov., Dz. (P.) habbachii, spec. nov., Dz. (P.) stenoptera, spec. nov., Dz. (P.) multiporosa, spec. nov., and Dz. (Monoscleroblatta) aglandulosa, spec. nov. The descriptions are illustrated by numerous figures and determination keys allow the discrimination of the species. The geographical distribution of the species is shown on several maps. The species of Pauciscleroblatta are distributed in Algeria, Tunisia, Israel, West Bank, Syria (Golan) and Cyprus, those of Monoscleroblatta are restricted to northwestern Morocco.
Stillbirth Among Arab Women in Canada, 1981-2015
Authors: Auger Nathalie , Racape Judith , Raynault Marie-France , Bilodeau-Bertrand Marianne , Lee Ga Eun , Janevic Teresa 
Published: January 2020

Objectives: The Arabic-speaking population is increasing in Europe and North America. Evidence suggests that Arab migrants have a greater risk of adverse birth outcomes than nonmigrants, but the risk of stillbirth is largely understudied. We examined inequality in stillbirth rates between Arab women and the French and English majority of women in Quebec, Canada. Methods: We conducted a retrospective study of all births in Quebec from 1981 through 2015. We computed stillbirth rates by period and cause of death, and we used log binomial regression to estimate the association between Arabic mother tongue and stillbirth, adjusted for maternal characteristics. Results: Stillbirth rates per 1000 births overall were lower among women with Arabic mother tongue (3.89) than among women with French or English mother tongue (4.52), and rates changed little over time. However, Arabic-speaking women from Arab countries had a higher adjusted risk of stillbirth than French- or English-speaking women (risk ratio = 1.23; 95% confidence interval, 1.07-1.42). Congenital anomalies, termination of pregnancy, and undetermined causes contributed to a disproportionate number of stillbirths among women with Arabic mother tongue compared with the French- and English-speaking majority. Conclusions: Arabic-speaking women from Arab countries have higher risks of stillbirth compared with the French and English majority in Quebec. Strategies to reduce stillbirth risk among Arabic speakers should focus on improving identification of causes of death.
Effect of a cognitive behavioural intervention on depression reduction among community-dwelling adult learners in Nigeria: Implications for adult education administration
Authors: Nwabuko Linus Okechukwu , Okechukwu Ann Ebere , Eneh Eberechukwu Charity , Eze Georgina Chinagorom , Eseabasi Favour Okon 
Published: January 2020

Objective The study objective was to determine the effect of a cognitive behavioural intervention (CBI) on depression among community-dwelling adult learners in Nigeria. Methods This was a 10-week randomized control trial. Participants were 82 community-dwelling adult learners with depression. The Beck Depression Inventory-II was used for data collection. Data were analysed using repeated measures analysis of variance. Results The initial results showed that the participants in both the treatment group and the usual care control group had severe depression. After 10 weeks of the CBI, there was a significant reduction in depression among adult learners in the treatment group compared with those in the usual care control group. The follow-up assessment indicated a further significant reduction in depression among participants in the treatment group compared with those in the control group. Conclusion The CBI was effective in reducing depression among community-dwelling university adult learners in Nigeria.
Resection of benign tumours of the submandibular gland with harmonic scalpel-assisted minimally extracapsular dissection
Authors: Hu Yongjie , Zheng Chongyang , Cao Rui , Hong Weisheng , Zhang Zhiyuan 
Published: January 2020

Objective This study was performed to compare the oncologic and functional outcomes in patients with benign submandibular gland (SMG) tumours after harmonic scalpel-assisted minimally extracapsular dissection (HS-MECD) or total gland excision (TGE). Methods In total, 133 consecutive patients who were preoperatively diagnosed with benign SMG tumours (pleomorphic adenoma, Warthin’s tumour, basal cell adenoma, or lymphoepithelial cyst) from 2013 to 2016 were included in this two-centre retrospective study. Sixty-four patients underwent HS-MECD and 69 patients underwent TGE. All tumours were within 4 cm. Surgical variables, complications, functional outcomes, and recurrence rates were evaluated. Results The operation time, blood loss, drainage time and volume, and length of hospital stay were significantly lower in the HS-MECD than TGE group. HS-MECD reduced local pain and transient facial nerve paralysis outcomes. Incision scars and facial deformities were less visible according to the visual analogue scale. No significant differences were found in either unstimulated or stimulated whole saliva at 1 month postoperatively, whilst higher unstimulated levels were detected in the HS-MECD group at 6 months. The recurrence rate was similar between the two groups. Conclusion For benign SMG tumours of <4 cm, HS-MECD represents a less invasive technique than TGE and affords patients increased postoperative functionality.
Renal pseudoaneurysm after blunt trauma in a 10-year-old girl: A case report
Authors: Sforza Simone , Persano Giorgio , Cini Chiara , Sforzi Idanna , Grosso Antonio Andrea , Bronzini Francesca , Bussolin Leonardo , Acquafresca Manlio , Masieri Lorenzo 
Published: January 2020

Introduction: Renal trauma is a relevant cause of morbidity in children older than 1 year. Most patients are currently managed conservatively, even in case of high-grade traumas; nevertheless, harmful complications may occur even in hemodynamically stable patients. We present a case of grade IV blunt renal trauma complicated by post-traumatic pseudoaneurysm. Case description: A 10-year-old girl was referred to our institution for grade IV trauma of the right kidney. During observation she had persistent hematuria that caused anemia. A second contrast-enhanced computed tomography scan revealed a posttraumatic pseudoaneurysm that was successfully treated by angiographic embolization. Conclusions: Although extremely rare after blunt renal trauma, post-traumatic renal pseudoaneurysm may cause severe blood loss and anemia, and angioembolization is therefore indicated. This condition should be suspected and move physicians to investigate further.
Burnout in Canadian Radiology Residency: A National Assessment of Prevalence and Underlying Contributory Factors
Authors: Ferguson Craig , Low Gavin , Shiau Gillian 
Published: January 2020

Objective: To determine burnout prevalence in Canadian radiology residency and identify contributing factors. Materials and Methods: A prospective 57-item survey, including the 22-item Maslach Burnout Inventory-Health Sciences Survey, was sent to all Canadian radiology residents, with a total resident population of 359. The association between emotional exhaustion (EE), depersonalization (DP), and personal achievement (PA) scores with items in the survey was performed. Continuous data were evaluated using the Student t test for comparing the means between the 2 groups or the analysis of variance test for comparing the means between at least 3 groups. Spearman correlation coefficient was performed when evaluating ordinal categorical data. Results: Response rate is 40.1% (n = 144); 50.7% of residents demonstrate high EE, 48.6% demonstrate high DP, and 35.9% demonstrate low PA. Being unhappy with residency and with radiology as a career is associated with burnout ( P < .001). Age, sex, marital status, and children have no impact on burnout. More hours worked is associated with higher EE ( P = .025) and DP ( P = .004). In all, 47.2% residents experienced intimidation or harassment. Feeling unsupported by staff radiologists is associated with higher EE ( P < .001), higher DP ( P = .001), and lower PA ( P = .008). In all, 45.1% of residents have poor work–life balance, and those residents demonstrate higher EE ( P < .001), higher DP ( P = .006), and lower PA ( P = .01). In all, 25% of residents identify poor education-service balance in their residency, and those residents have higher EE ( P < .001), higher DP ( P = .042), and lower PA ( P = .005). Conclusion: This study demonstrates significant burnout in Canadian radiology residents with major contributory factors identified.
Designing meditation for doctor well-being: can ‘Om’ help obstetrics and gynaecology doctors?
Authors: Allen Rosie , Robinson Andrew , Allen Shelley , Nathan Elizabeth , Coghlan Edwina , Leung Yee 
Published: January 2020

Objective: The study aimed to measure the impact of meditation on participants’ ability to regulate brain wave activity in high-stress situations, control physiological stress responses and improve subjective wellbeing. Methods: Twelve obstetrics and gynaecology (O&G) doctors meditated for 20 minutes daily for 21 days utilising a portable EEG (electroencephalogram) providing instantaneous audio feedback. Their brain activity levels and salivary cortisol were measured before and after performing three surgical procedures. Participants were interviewed about their experiences and completed self-ratings of distress (e.g. DASS-21, Depression, Anxiety and Depression Scale). Data were analysed statistically and thematically. Results: (a) Measures of pre- and post-operative brain activity showed no significantly higher levels of alpha waves. (b) Pre- and post-operative salivary cortisol levels did not significantly decrease. (c) DASS-21 scores showed significant decreases in levels of anxiety and stress. Conclusion: Results suggest that, with biofeedback meditation, O&G doctors can learn to reduce situational stress and improve mood overall through a focussed intervention.
The migration pattern and initial stability of the Optimys short stem in total hip arthroplasty: a prospective 2-year follow-up study of 33 patients with RSA
Authors: de Waard Sheryl , Sierevelt Inger N , Jonker Renee , Hoornenborg Daniel , van der Vis Harm M , Kerkhoffs Gino M M J , Haverkamp Daniël 
Published: January 2020

Background and purpose: The consensus that bone stock preservation and optimal restoration of offset and leg length is important in total hip arthroplasty is now widespread, especially for young and active patients. Short stems seem promising in this aspect, though implant stability is still of concern. This study looked at the migration pattern of the Optimys short stem through RSA analysis. Patients and methods: 40 patients were included. RSA images were made directly postoperatively (within 5 days), at 6 weeks and at 3, 6, 12 and 24 months. Double examinations were made for precision measurement. HOOS and pain scores were obtained preoperatively and at 2 years. 4 patients were excluded due to protocol violation and 1 patient was excluded for RSA analysis with a CN number >110. 2 patients were lost to follow-up after 3 and 6 months ( n  = 1 lost, n  = 1 deep infection, respectively). Results: Mean age was 60 years with a mean BMI of 27. RSA analysis of 34 patients showed a significant initial median proximodistal translation (subsidence) of 0.21 mm (IQR 0.64–0.06) and anteversion-retroversion rotation of 0.59° (IQR 0.01–1.34) at 6 weeks, after which the stem stabilises and showed no further significant movement. Median migration in other directions was small. 4 patients had an initial subsidence of >2 mm, all showed secondary stabilisation. HOOS outcomes were satisfactory, with the domain symptoms and pain showing a median score of 95/100 at 2 years. Conclusions: After initial migration the Optimys achieves secondary stabilisation, suggesting low risk on long-term aseptic loosening. Clinical trials registration: NL47055.048.13.