bluuebunny/crossref_metadata_2025 huggingface dataset:
Radiation-induced cavernous malformation after stereotactic radiosurgery for cavernous sinus meningioma: a case report
Authors: Yu Zuan , Huang Bin , Liang Risheng
Published: November 2020

Background

Radiation-induced cavernous malformation (RICM) is a rare sequela of stereotactic radiosurgery (SRS) treatment of intracranial tumors. To date, no study reported on RICM after SRS for meningiomas originating from the skull base. The relationship between locus of initial meningioma and RICM has not been studied.

Case presentation

A 57-year-old woman presented with persistent headaches and blepharoptosis at initial episode. MRI disclosed a right parasellar lesion, diagnosed as a cavernous sinus meningioma (CSM). After receiving a single-fractionated SRS, headache relieved, but blepharoptosis did not significantly improve. Three years and three months later, she returned with headaches and dizziness. MRI showed an enlarged CSM. Moreover, a new mass-like lesion, suspected hemangioma, appeared in the nearby right temporal lobe. After surgical removal of the new lesion and the CSM, the patient’s neurological symptoms significantly improved. Pathology confirmed CSM and temporal RICM.

Conclusions

We report the first rare case of RICM occurring after SRS for CSM. The RICM may be in the same region as the initial tumor. Surgical intervention was preferred for symptomatic RICM and initial meningioma. We recommend long-term regular followup MRIs for patients with meningioma after SRS treatment.
The first evidence for SLFN11 expression as an independent prognostic factor for patients with esophageal cancer after chemoradiotherapy
Authors: Kagami Takuma , Yamade Mihoko , Suzuki Takahiro , Uotani Takahiro , Tani Shinya , Hamaya Yasushi , Iwaizumi Moriya , Osawa Satoshi , Sugimoto Ken , Miyajima Hiroaki , Baba Satoshi , Sugimura Haruhiko , Murai Junko , Pommier Yves , Furuta Takahisa
Published: November 2020

Background

Schlafen 11 (SLFN11) was recently identified as a dominant determinant of sensitivity to DNA-targeting agents including platinum-based drugs. SLFN11 also reportedly enhances cellular radiosensitivity. In this study, we examined the prognostic value of SLFN11 expression in esophageal squamous cell carcinoma (ESCC) patients treated with definitive chemoradiotherapy (dCRT), including the platinum derivative nedaplatin.

Methods

Seventy-three patients with ESCC who received dCRT were examined. SLFN11 expression was analyzed in pre-dCRT biopsies using immunohistochemistry and evaluated using a histo-score (H-score). Correlation between the H-score and overall survival was analyzed. An H-score ≥ 51 was provisionally defined as indicating high SLFN11 expression. Viability assays were performed using previously established isogenic human cell lines differentially expressing SLFN11 to test the usefulness of SLFN11 as marker of response to the dCRT regimen.

Results

High SLFN11 expression was independently associated with better prognosis in ESCC patients (hazard ratio = 0.295, 95% CI = 0.143–0.605, p = 0.001 for multivariate analysis). Kaplan-Meier survival curves showed that the prognostic value of high SLFN11 expression was most evident in patients at clinical stages II and III (p = 0.004). In in vitro study, SLFN11-proficient cells were highly sensitive to platinum derivatives compared to SLFN11-deficient cells.

Conclusion

SLFN11 expression is an independent prognostic factor for ESCC patients treated with dCRT and a potential biomarker for treatment selection of ESCC. Examination of SLFN11 may be particularly useful for clinical Stage II–III patients who wish to choose dCRT (instead of surgery) to preserve esophageal function.
Breast cancer distant recurrence lead time interval by detection method in an institutional cohort
Authors: Kaplan Henry G. , Malmgren Judith A. , Atwood Mary K.
Published: November 2020

Background

Lead time, the interval between screen detection and when a disease would have become clinically evident, has been cited to explain longer survival times in mammography detected breast cancer cases (BC).

Methods

An institutional retrospective cohort study of BC outcomes related to detection method (mammography (MamD) vs. patient (PtD)). Cases were first primary invasive stage I-III BC, age 40–74 years (n = 6603), 1999–2016. Survival time was divided into 1) distant disease-free interval (DDFI) and 2) distant disease-specific survival (DDSS) as two separate time interval outcomes. We measured statistical association between detection method and diagnostic, treatment and outcome variables using bivariate comparisons, Cox proportional hazards analyses and mean comparisons. Outcomes were distant recurrence (n = 422), DDFI and DDSS.

Results

39% of cases were PtD (n = 2566) and 61% were MamD (n = 4037). MamD cases had a higher percentage of Stage I tumors [MamD 69% stage I vs. PtD 31%, p < .001]. Rate of distant recurrence was 11% among PtD BC cases (n = 289) vs. 3% of MamD (n = 133) (p < .001). Order of factor entry into the distant recurrence time interval (DDFI) model was 1) TNM stage (p < .001), 2) HR/HER2 status (p < .001), 3) histologic grade (p = .005) and 4) detection method (p < .001). Unadjusted PtD DDFI mean time was 4.34 years and MamD 5.52 years (p < .001), however when stratified by stage, the most significant factor relative to distant recurrence, there was no significant difference between PtD and MamD BC. Distant disease specific survival time did not differ by detection method.

Conclusion

We observed breast cancer distant disease-free interval to be primarily associated with stage at diagnosis and tumor characteristics with less contribution of detection method to the full model. Patient and mammography detected breast cancer mean lead time to distant recurrence differed significantly by detection method for all stages but not significantly within stage with no difference in time from distant recurrence to death. Lead time difference related to detection method appears to be present but may be less influential than other factors in distant disease-free and disease specific survival.
Dynamics on the field: a focused study on the culture and context of pediatric pain management at four Ghanaian hospitals
Authors: Kusi Amponsah Abigail , Oduro Evans , Bam Victoria , Kyei-Dompim Joana , Ahoto Collins Kwadwo , Axelin Anna
Published: November 2020

Background

As part of efforts to develop and implement a short course educational program on pediatric pain management, the current study sought to understand the culture and contextual factors that influence children’s pain management in order to improve the practice in pediatric care settings.

Methods

Guided by Bourdieu’s theory of practice, a focused ethnographic study was conducted from October, 2018 to February, 2019. The study was contextualized at four Ghanaian hospitals among purposefully sampled nurses, physicians, hospitalized children and their families. During the 20-week study period, three ethnographers spent 144 h conducting participant-observation sessions. Formal and informal interviews were held with participants in addition to review of hospital records.

Results

Analysis of the field data resulted in four themes. “Children’s pain expression and response of caregivers” described the disposition (habitus) of both children and caregivers to act in particular ways due to children’s incomplete health status (bodily capital) which caused them pain and also resulted in discomforting procedures. “Pharmacological pain management practices and attitudes” elucidated the use of analgesics as the mainstay disposition (habitus) in children’s pain management due to high level of respect (symbolic capital) given to such interventions on the pediatric units (field). “Managing pain without drugs” illustrated healthcare providers and family caregivers’ disposition (habitus) of using diverse nonpharmacological methods in managing children’s pain. “Communication and interaction between pain actors” depicted how children’s access to care givers (social capital) can serve as a powerful tool in influencing pediatric pain assessment and management disposition (habitus) on the pediatric units (field).

Conclusions

The habitus of pediatric pain actors toward pain assessment and management practices are influenced by various forms of capital (social, cultural, symbolic, bodily and economic) operating at different levels on the pediatric care field. Quality improvement programs that seek to enhance pediatric pain management should use the insights obtained in this study to guide the development, implementation and evaluation stages.
Correction to: South Africa’s new standard material transfer agreement: proposals for improvement and pointers for implementation
Authors: Thaldar Donrich W. , Botes Marietjie , Nienaber Annelize
Published: November 2020

An amendment to this paper has been published and can be accessed via the original article.
Review of evolution of the public long-term care insurance (LTCI) system in different countries: influence and challenge
Authors: Chen Linhong , Zhang Lu , Xu Xiaocang
Published: November 2020

Background

The growing demand for LTC (Long-term care) services for disabled elderly has become a daunting task for countries worldwide, especially China, where population aging is particularly severe. According to CSY (China Statistical Yearbook,2019), the elderly aged 65 or above has reached 167 million in 2018, and the number of disabled elderly is as high as 54%. Germany and other countries have alleviated the crisis by promoting the public LTCI (Long-Term Care Insurance) system since the 1990s, while China’s public LTCI system formal pilot only started in 2016. Therefore, the development of the public LTCI system has gradually become a hot topic for scholars in various countries, including China.

Methods

This review has been systematically sorted the existing related literature to discuss the development of public LTCI (Long-Term Care Insurance)system form four aspects, namely, the comparison of public LTCI systems in different countries, the influence of public LTCI, challenge of public LTCI, and the relationship between public LTCI and private LTCI. We searched some databases including Web of Science Core Collection, Medline, SCOPUS, EBSCO, EMBASE, ProQuest and PubMed from January 2008 to September 2020. The quality of 38 quantitative and 21 qualitative articles was evaluated using the CASP(Critical Appraisal Skills Programme) critical evaluation checklist.

Results

The review systematically examines the development of public LTCI system from four aspects, namely, the comparison of public LTCI systems in different countries, the influence of public LTCI, the challenge of public LTCI, and the relationship between public LTCI and private LTCI. For example, LTCI has a positive effect on the health and life quality of the disabled elderly. However, the role of LTCI in alleviating the financial burden on families with the disabled elderly may be limited.

Conclusion

Some policy implications on the future development of China’s LTCI system can be obtained. For example, the government should fully consider the constraints such as price rise, the elderly disability rate, and the substantial economic burden. It also can strengthen the effective combination of public LTCI and private LTCI. It does not only help to expand the space for its theoretical research but also to learn the experiences in the practice of the LTCI system in various countries around the world. It will significantly help the smooth development and further promote the in-depth reform of the LTCI system in China.
Professionals’ perceptions of the establishment of a specialized brief therapy unit in a district psychiatric centre - a qualitative study
Authors: Markussen Hilde V. , Aasdahl Lene , Rise Marit B.
Published: November 2020

Background

Increasing mental health problems and scarce treatment resources put pressure on mental health services to make innovations in service provision, such as developing differentiated services adapted to different needs. One innovation in differentiated service provision is brief or short-term treatment to patients with moderate mental health problems. Implementing a new unit in an organization usually faces many potential barriers and facilitators, and knowledge on how the professionals providing the services perceive the implementation of innovative approaches in mental health services is scarce. The aim of this study was therefore to explore the professionals’ perceptions of how the establishment of a specialized brief therapy unit had affected the organization, especially the everyday work in the outpatient clinics.

Methods

Eleven professionals, five men and six women, took part in individual interviews. All participants were between 40 and 60 years old and had leading or coordinating positions in the organization. Their professional backgrounds were within psychology, nursing and medicine, most of them specialists in their field. Data was analyzed according to Systematic text condensation.

Results

The professionals’ experiences represented four main themes: (1) The brief therapy unit was perceived as successful and celebrated. (2) The general outpatient clinics, on the other hand, were described as “forgotten”. (3) The establishment process had elucidated different views on treatment in the outpatient clinics - and had set off (4) a discussion regarding the criteria for prioritizing in mental health services.

Conclusion

Providing targeted treatment to patients with moderate mental health problems, while having a concurrent aim to solve broader problems in mental health services, entails a discussion regarding resource use and the appropriate level of treatment provision. Professionals should be more involved when innovative efforts are implemented, and the criteria for success must be conceptualized and evaluated. Longitudinal research on the implementation of innovative efforts in the services should include professionals’ and service users’ perspectives.
A 300-kb microduplication of 7q36.3 in a patient with triphalangeal thumb-polysyndactyly syndrome combined with congenital heart disease and optic disc coloboma: a case report
Authors: Zlotina Anna , Melnik Olesia , Fomicheva Yulia , Skitchenko Rostislav , Sergushichev Alexey , Shagimardanova Elena , Gusev Oleg , Gazizova Guzel , Loevets Tatiana , Vershinina Tatiana , Kozyrev Ivan , Gordeev Mikhail , Vasichkina Elena , Pervunina Tatiana , Kostareva Anna
Published: November 2020

Background

Triphalangeal thumb-polysyndactyly syndrome (TPT-PS) is a rare well-defined autosomal dominant disorder characterized by long thumbs with three phalanges combined with pre- and postaxial polydactyly/syndactyly of limbs. By now, the syndrome has been reported in several large families from different ethnic backgrounds, with a high degree of inter- and intrafamilial variability. The genome locus responsible for TPT-PS has been mapped to the 7q36.3 region harboring a long-range sonic hedgehog (SHH) regulatory sequence (ZRS). Both single-nucleotide variants and complete duplications of ZRS were shown to cause TPT-PS and similar limb phenotypes. TPT-PS usually forms as isolated limb pathology not associated with additional malformations, in particular, with cardiovascular abnormalities.

Case presentation

Here we report on a rare Russian neonatal case of TPT-PS combined with severe congenital heart disease, namely double outlet right ventricle, and microphthalmia with optic disc coloboma. Pedigree analysis revealed TPT-PS of various expressivity in 10 family members throughout five generations, while the cardiac defect and the eye pathology were detected only in the proband. To extend the knowledge on genotype–phenotype spectrum of TPT-PS, the careful clinical and genomic analysis of the family was performed. High-resolution array-based comparative genomic hybridization (array-CGH) revealed a ~ 300 kb microduplication of 7q36.3 locus (arr[GRCh37] 7q36.3(156385810_156684811) × 3) that co-segregated with TPT-PS in the proband and her mother. The duplication encompassed three genes includingLMBR1, the intron 5 of which is known to harbor ZRS. Based on whole-exome sequencing data, no additional pathogenic mutations or variants of uncertain clinical significance were found in morbid cardiac genes or genes associated with a microphthalmia/anophthalmia/coloboma spectrum of ocular malformations.

Conclusions

The results support the previous data, indicating that complete ZRS duplication underlies TPT-PS, and suggest a broader phenotypic impact of the 7q36.3 microduplication. Potential involvement of the 7q36.3 microduplication in the patient’s cardiac and eye malformations is discussed. However, the contribution of some additional genetic/epigenetic factors to the complex patient`s phenotype cannot be excluded entirely. Further comprehensive functional studies are needed to prove the possible involvement of the 7q36.3 locus in congenital heart disease and eye pathology.
Extracellular vesicle-associated miR-135b and -135a regulate stemness in Group 4 medulloblastoma cells by targeting angiomotin-like 2
Authors: Choi Seung Ah , Koh Eun Jung , Kim Ryong Nam , Byun Jung Woo , Phi Ji Hoon , Yang Jeyul , Wang Kyu-Chang , Park Ae Kyung , Hwang Do Won , Lee Ji Yeoun , Kim Seung-Ki
Published: November 2020

Background

Extracellular vesicles (EVs) secreted by tumours, including exosomes, are important factors that regulate cell–cell interactions in oncogenesis. Although EV studies are ongoing, the biological understanding of EV-miRNAs derived from brain tumour spheroid-forming cells (BTSCs) of medulloblastoma is poor.

Purposes

We explored the specific cellular miRNAs and EV-miRNAs in medulloblastoma BTSCs to determine their potential biological function.

Methods

Bulk tumor cells (BTCs) and BTSCs were cultured under different conditions from medulloblastoma tissues (N = 10).

Results

Twenty-four miRNAs were simultaneously increased in both cells and EVs derived from BTSCs in comparison to BTCs. After inhibition of miR-135b or miR135a which were the most significantly increased in BTSCs, cell viability, self-renewal and stem cell marker expression decreased remarkably. Through integrated analysis of mRNAs and miRNAs data, we found that angiomotin-like 2 (AMOTL2), which was significantly decreased, was targeted by both miR-135b and miR-135a. STAT6 and GPX8 were targeted only by miR-135a. Importantly, low expression of AMOTL2 was significantly associated with overall poor survival in paediatric Group 3 and Group 4 medulloblastoma patients.

Conclusion

Our results indicated that inhibition of miR-135b or miR-135a leads to suppress stemness of BTSC through modulation of AMOTL2.
Differential expression of Oct-4, CD44, and E-cadherin in eutopic and ectopic endometrium in ovarian endometriomas and their correlations with clinicopathological variables
Authors: Sancakli Usta Ceyda , Turan Gulay , Bulbul Cagla Bahar , Usta Akin , Adali Ertan
Published: November 2020

Background

Endometriosis is an estrogen-dependent inflammatory disease that often causes infertility and chronic pelvic pain. Although endometriosis is known as a benign disease, it has demonstrated characteristics of malignant neoplasms, including neoangiogenesis, tissue invasion, and cell implantation to distant organs. Octamer-binding protein 4 (Oct-4) is a molecular marker for stem cells that plays an essential role in maintaining pluripotency and self–renewal processes in various types of benign and malignant tissues. CD44 is a multifunctional cell surface adhesion molecule that acts as an integral cell membrane protein and plays a role in cell–cell and cell–matrix interactions. E-cadherin is an epithelial cell–cell adhesion molecule that plays important role in the modulation of cell polarization, cell migration, and cancer metastasis. The aim of this study was to investigate the expression patterns of Oct-4, CD44, and E-cadherin in eutopic and ectopic endometrial tissues from women with endometrioma compared to control endometrial tissues from women without endometrioma.

Methods

In the present study, Oct-4, CD44, and E-cadherin expressions were evaluated in eutopic and ectopic endometrial tissue samples from women with endometrioma (n = 32) and compared with those of control endometrial tissue samples from women without endometrioma (n = 30).

Results

Immunohistochemical expression of Oct-4 was significantly higher in the ectopic endometrial tissue samples of women with endometrioma than in the control endometrial tissue samples (p = 0.0002). Conversely, CD44 and E-cadherin expressions were significantly lower in the ectopic endometrial tissue samples of women with endometrioma than in the control endometrial tissue samples (p = 0.0137 andp = 0.0060, respectively). Correlation analysis demonstrated significant correlations between Oct-4 expression and endometrioma cyst diameter (p = 0.0162), rASRM stage (p = 0.0343), and total rASRM score (p = 0.0223). Moreover, CD44 expression was negatively correlated with the presence of peritoneal endometriotic lesions (p = 0.0304) while E-cadherin expression was negatively correlated with the presence of deep infiltrating endometriosis (p = 0.0445).

Conclusions

Increased expression of Oct-4 and decreased expression of adhesion molecules in endometriotic tissues may contribute to the development and progression of endometriosis.
Workplace neighbourhood built environment and workers’ physically-active and sedentary behaviour: a systematic review of observational studies
Authors: Lin Chien-Yu , Koohsari Mohammad Javad , Liao Yung , Ishii Kaori , Shibata Ai , Nakaya Tomoki , McCormack Gavin R. , Hadgraft Nyssa , Owen Neville , Oka Koichiro
Published: November 2020

Background

Many desk-based workers can spend more than half of their working hours sitting, with low levels of physical activity. Workplace neighbourhood built environment may influence workers’ physical activities and sedentary behaviours on workdays. We reviewed and synthesised evidence from observational studies on associations of workplace neighbourhood attributes with domain-specific physical activity and sedentary behaviour and suggested research priorities for improving the quality of future relevant studies.

Methods

Published studies were obtained from nine databases (PubMed, Web of Science, PsycINFO, Scopus, Transport Research International Documentation, MEDLINE, Cochrane, Embase, and CINAHL) and crosschecked by Google Scholar. Observational studies with quantitative analyses estimating associations between workplace neighbourhood built environment attributes and workers’ physical activity or sedentary behaviour were included. Studies were restricted to those published in English language peer-reviewed journals from 2000 to 2019.

Results

A total of 55 studies and 455 instances of estimated associations were included. Most instances of potential associations of workplace neighbourhood built environment attributes with total or domain-specific (occupational, transport, and recreational) physical activity were non-significant. However, destination-related attributes (i.e., longer distances from workplace to home and access to car parking) were positively associated with transport-related sedentary behaviour (i.e., car driving).

Conclusions

The findings reinforce the case for urban design policies on designing mixed-use neighbourhoods where there are opportunities to live closer to workplaces and have access to a higher density of shops, services, and recreational facilities. Studies strengthening correspondence between the neighbourhood built environment attributes and behaviours are needed to identify and clarify potential relationships.

Protocol registration

The protocol of this systematic review was registered on the International Prospective Register of Systematic Reviews (PROSPERO) on 2 December 2019 (registration number: CRD42019137341).
Autoimmune hemolytic anemia: current knowledge and perspectives
Authors: Michalak Sylwia Sulimiera , Olewicz-Gawlik Anna , Rupa-Matysek Joanna , Wolny-Rokicka Edyta , Nowakowska Elżbieta , Gil Lidia
Published: November 2020

Autoimmune hemolytic anemia (AIHA) is an acquired, heterogeneous group of diseases which includes warm AIHA, cold agglutinin disease (CAD), mixed AIHA, paroxysmal cold hemoglobinuria and atypical AIHA. Currently CAD is defined as a chronic, clonal lymphoproliferative disorder, while the presence of cold agglutinins underlying other diseases is known as cold agglutinin syndrome. AIHA is mediated by autoantibodies directed against red blood cells (RBCs) causing premature erythrocyte destruction. The pathogenesis of AIHA is complex and still not fully understood. Recent studies indicate the involvement of T and B cell dysregulation, reduced CD4+ and CD25+ Tregs, increased clonal expansions of CD8 + T cells, imbalance of Th17/Tregs and Tfh/Tfr, and impaired lymphocyte apoptosis. Changes in some RBC membrane structures, under the influence of mechanical stimuli or oxidative stress, may promote autohemolysis. The clinical presentation and treatment of AIHA are influenced by many factors, including the type of AIHA, degree of hemolysis, underlying diseases, presence of concomitant comorbidities, bone marrow compensatory abilities and the presence of fibrosis and dyserthropoiesis. The main treatment for AIHA is based on the inhibition of autoantibody production by mono- or combination therapy using GKS and/or rituximab and, rarely, immunosuppressive drugs or immunomodulators. Reduction of erythrocyte destruction via splenectomy is currently the third line of treatment for warm AIHA. Supportive treatment including vitamin supplementation, recombinant erythropoietin, thrombosis prophylaxis and the prevention and treatment of infections is essential. New groups of drugs that inhibit immune responses at various levels are being developed intensively, including inhibition of antibody-mediated RBCs phagocytosis, inhibition of B cell and plasma cell frequency and activity, inhibition of IgG recycling, immunomodulation of T lymphocytes function, and complement cascade inhibition. Recent studies have brought about changes in classification and progress in understanding the pathogenesis and treatment of AIHA, although there are still many issues to be resolved, particularly concerning the impact of age-associated changes to immunity.
Displacement in root apex and changes in incisor inclination affect alveolar bone remodeling in adult bimaxillary protrusion patients: a retrospective study
Authors: Mao Huimin , Yang Andi , Pan Yue , Li Houxuan , Lei Lang
Published: November 2020

Background

Periodontal health is of great concern for periodontists and orthodontists in the inter-disciplinary management of patients with bimaxillary protrusion. The aim of present study is to investigate changes in the alveolar bone in the maxillary incisor region and to explore its relationship with displacement of root apex as well as changes in the inclination of maxillary incisors during incisor retraction.

Methods

Samples in this retrospective study consisted of 38 patients with bimaxillary protrusion. Cone-beam computed tomography (CBCT) images was taken before(T0) and after (T1) treatment. Alveolar bone thickness (ABT), height (ABH) and area (ABA) were utilized to evaluate changes in the alveolar bone, while incisor inclination and apex displacement were used to assess changes in the position of maxillary central and lateral incisors. Correlations between alveolar bone remodeling and apex displacement as well as changes in the inclination were investigated.

Results

The labial ABT of central and lateral incisors at the mid-root third was increased. In contrast, the palatal ABT at crestal, mid-root and apical third level were consistently decreased. ABH was not altered on the labial side, while significantly decreased on the palatal side. ABA was not significantly increased on the labial side, but significantly decreased on the palatal side, leading to a significantly reduced total ABA. Orthodontic treatment significantly reduced inclination of upper incisors. Changes in the amount (T1-T0) of ABA was remarkably correlated with apex displacement and changes of inclination (T1-T0); in addition, using the multivariate linear regression analysis, changes of ABA on the palatal side (T1-T0) can be described by following equation: Changes of palatal ABA (T1-T0) = − 3.258- 0.139× changes of inclination (T1-T0) + 2.533 × apex displacement (T1-T0).

Conclusions

Retraction of incisors in bimaxillary protrusion patients may compromise periodontal bone support on the palatal side. An equation that incorporated the displacement of root apex and change in the incisor inclination may enable periodontist-orthodontist interdisciplinary coordination in assessing treatment risks and developing an individualized treatment plan for adult patients with bimaxillary protrusion. Moreover, the equation in predicating area of alveolar bone may reduce the risks of placing the teeth out of the bone boundary during 3D digital setups.
Single cell characterization of B-lymphoid differentiation and leukemic cell states during chemotherapy in ETV6-RUNX1-positive pediatric leukemia identifies drug-targetable transcription factor activities
Authors: Mehtonen Juha , Teppo Susanna , Lahnalampi Mari , Kokko Aleksi , Kaukonen Riina , Oksa Laura , Bouvy-Liivrand Maria , Malyukova Alena , Mäkinen Artturi , Laukkanen Saara , Mäkinen Petri I. , Rounioja Samuli , Ruusuvuori Pekka , Sangfelt Olle , Lund Riikka , Lönnberg Tapio , Lohi Olli , Heinäniemi Merja
Published: November 2020

Background

Tight regulatory loops orchestrate commitment to B cell fate within bone marrow. Genetic lesions in this gene regulatory network underlie the emergence of the most common childhood cancer, acute lymphoblastic leukemia (ALL). The initial genetic hits, including the common translocation that fusesETV6andRUNX1genes, lead to arrested cell differentiation. Here, we aimed to characterize transcription factor activities along the B-lineage differentiation trajectory as a reference to characterize the aberrant cell states present in leukemic bone marrow, and to identify those transcription factors that maintain cancer-specific cell states for more precise therapeutic intervention.

Methods

We compared normal B-lineage differentiation and in vivo leukemic cell states using single cell RNA-sequencing (scRNA-seq) and several complementary genomics profiles. Based on statistical tools for scRNA-seq, we benchmarked a workflow to resolve transcription factor activities and gene expression distribution changes in healthy bone marrow lymphoid cell states. We compared these to ALL bone marrow at diagnosis and in vivo during chemotherapy, focusing on leukemias carrying theETV6-RUNX1fusion.

Results

We show that lymphoid cell transcription factor activities uncovered from bone marrow scRNA-seq have high correspondence with independent ATAC- and ChIP-seq data. Using this comprehensive reference for regulatory factors coordinating B-lineage differentiation, our analysis ofETV6-RUNX1-positive ALL cases revealed elevated activity of multiple ETS-transcription factors in leukemic cells states, including the leukemia genome-wide association study hit ELK3. The accompanying gene expression changes associated with natural killer cell inactivation and depletion in the leukemic immune microenvironment. Moreover, our results suggest that the abundance of G1 cell cycle state at diagnosis and lack of differentiation-associated regulatory network changes during induction chemotherapy represent features of chemoresistance. To target the leukemic regulatory program and thereby overcome treatment resistance, we show that inhibition of ETS-transcription factors reduced cell viability and resolved pathways contributing to this using scRNA-seq.

Conclusions

Our data provide a detailed picture of the transcription factor activities characterizing both normal B-lineage differentiation and those acquired in leukemic bone marrow and provide a rational basis for new treatment strategies targeting the immune microenvironment and the active regulatory network in leukemia.
Correction to: Microfluidic resonators with two parallel channels for independent sample loading and effective density tuning
Authors: Lee Jungchul , Khan Faheem , Thundat Thomas , Lee Bong Jae
Published: November 2020

An amendment to this paper has been published and can be accessed via the original article.
Potential of deep predictive coding networks for spatiotemporal tsunami wavefield prediction
Authors: Fauzi Ardiansyah , Mizutani Norimi
Published: November 2020

Data assimilation is a powerful tool for directly forecasting tsunami wavefields from the waveforms recorded at dense observational stations like S-Net without the need to know the earthquake source parameters. However, this method requires a high computational load and a quick warning is essential when a tsunami threat is near. We propose a new approach based on a deep predictive coding network for forecasting spatiotemporal tsunami wavefields. Unlike the previous data assimilation method, which continuously computes the wavefield when observed data are available, we use only a short sequence from previously assimilated wavefields to forecast the future wavefield. Since the predictions are computed through matrix multiplication, the future wavefield can be estimated in seconds. We apply the proposed method to simple bathymetry and the 2011 Tohoku tsunami. The results show that our proposed method is very fast (1.6 s for 32 frames of prediction with 1-min interval) and comparable to the previous data assimilation. Therefore, the proposed method is promising for integration with data assimilation to reduce the computational cost.
Stationarity of spot freight rates considering supply/demand effect
Authors: Hayashi Koichiro
Published: November 2020

The mean-reverting nature of freight rates is one of the important subjects in maritime economics. The classic understanding of maritime economics (and that of the shipping industry) suggests that freight rate processes are mean-reverting and approach the level decided by the demand/supply ratio. However, statistical tests on freight rate processes often reveal these processes to be non-stationary, which means the processes would not have a mean-reverting nature. In this study, we investigated the mean-reverting nature of Panamax freight rates (Baltic Panamax 4 T/C Average) for two “means”: the actual freight rate process itself, and the deviation process of actual freight rates from estimated ones based on the demand/supply ratio. The AR (1) model can be applied to both processes, and their autoregressive coefficient φ was between 0 and 1. In the actual freight process, φ was close to 1, and a unit root test failed to reject that the process is non-stationary. By contrast, in the deviation process, φ was sufficiently smaller than 1, and a unit root test rejected that the process is non-stationary. The result can resolve the contradiction between two views on mean-reverting nature; if we focus on the actual freight rate process itself and do not consider demand/supply, the process is non-stationary and does not have a mean-reverting nature. If we focus on the deviation process of the actual freight rates from the level decided by the demand/supply ratio, the process is stationary and tends to approach zero.
Modeling of moral decisions with deep learning
Authors: Wiedeman Christopher , Wang Ge , Kruger Uwe
Published: November 2020

One example of an artificial intelligence ethical dilemma is the autonomous vehicle situation presented by Massachusetts Institute of Technology researchers in the Moral Machine Experiment. To solve such dilemmas, the MIT researchers used a classic statistical method known as the hierarchical Bayesian (HB) model. This paper builds upon previous work for modeling moral decision making, applies a deep learning method to learn human ethics in this context, and compares it to the HB approach. These methods were tested to predict moral decisions of simulated populations of Moral Machine participants. Overall, test results indicate that deep neural networks can be effective in learning the group morality of a population through observation, and outperform the Bayesian model in the cases of model mismatches.
Reduction of coercive measures under routine conditions in psychiatric hospitals 2004–2019: Strong effects in old age psychiatry, much less in general psychiatry
Authors: Steinert Tilman , Hirsch Sophie , Goebel Rita , Snellgrove Brendan , Flammer Erich
Published: November 2020

Background

Many interventions to reduce the use of seclusion and restraint have been suggested in the last decades. Evidence-based interventions in old age psychiatry are different from those in general psychiatry. A common database for psychiatric hospitals introduced in 2004 allowed to examine the use of seclusion and restraint over 16 years under routine conditions.

Methods

A registry for coercive measures in the Federal State of Baden-Wuerttemberg has been available since 2015, and comprises all 32 hospitals licensed to admit involuntary patients. A study group had collected data prospectively since 2004 from a subsample of these hospitals. We analyzed the mean percentage of patients subjected to coercive measures and the mean cumulative duration of these interventions in ICD-10 diagnostic groups in psychiatric hospitals from 2004 to 2019 among a total of 1,038,239 admissions.

Results

The proportion of cases affected by coercive measures dropped significantly from 28.4 to 10.5% in patients with ICD-10 F0 disorders, while rates in patients with other diagnoses decreased insignificantly from 7.0 to 5.4%. The cumulated duration of coercive measures per affected case also dropped significantly among patients with F0 disorders, while changes in patients with other diagnoses remained insiginficant.

Conclusions

The use of coercive measures in patients with organic disorders could be reduced by about 50% in a State of 11 million inhabitants within 15 years, while in contrast no substantial reduction occurred among all other diagnostic groups. Specific interventions to reduce coercive interventions seem to be particularly successful for this patient group.
Impact of High-Dose-Rate Brachytherapy Training via Telehealth in Low- and Middle-Income Countries
Authors: Hatcher Jeremy B. , Oladeru Oluwadamilola , Chang Betty , Malhotra Sameeksha , Mcleod Megan , Shulman Adam , Dempsey Claire , Mula-Hussain Layth , Tassoto Michael , Sandwall Peter , Dieterich Sonja , Sulieman Lina , Roa Dante , Li Benjamin
Published: November 2020

PURPOSE

Our objective was to demonstrate the efficacy of a telehealth training course on high-dose-rate (HDR) brachytherapy for gynecologic cancer treatment for clinicians in low- and middle-income countries (LMICs)

METHODS

A 12-week course consisting of 16 live video sessions was offered to 10 cancer centers in the Middle East, Africa, and Nepal. A total of 46 participants joined the course, and 22 participants, on average, attended each session. Radiation oncologists and medical physicists from 11 US and international institutions prepared and provided lectures for each topic covered in the course. Confidence surveys of 15 practical competencies were administered to participants before and after the course. Competencies focused on HDR commissioning, shielding, treatment planning, radiobiology, and applicators. Pre- and post-program surveys of provider confidence, measured by 5-point Likert scale, were administered and compared.

RESULTS

Forty-six participants, including seven chief medical physicists, 16 senior medical physicists, five radiation oncologists, and three dosimetrists, representing nine countries attended education sessions. Reported confidence scores, both aggregate and paired, demonstrated increases in confidence in all 15 competencies. Post-curriculum score improvement was statistically significant ( P < .05) for paired respondents in 11 of 15 domains. Absolute improvements were largest for confidence in applicator commissioning (2.3 to 3.8, P = .009), treatment planning system commissioning (2.2 to 3.9, P = .0055), and commissioning an HDR machine (2.2 to 4.0, P = .0031). Overall confidence in providing HDR brachytherapy services safely and teaching other providers increased from 3.1 to 3.8 and 3.0 to 3.5, respectively.

CONCLUSION

A 12-week, low-cost telehealth training program on HDR brachytherapy improved confidence in treatment delivery and teaching for clinicians in 10 participating LMICs.
The Contribution of Transcriptional Coregulators in the Maintenance of β-cell Function and Identity
Authors: Davidson Rebecca K , Kanojia Sukrati , Spaeth Jason M
Published: November 2020

Islet β-cell dysfunction that leads to impaired insulin secretion is a principal source of pathology of diabetes. In type 2 diabetes, this breakdown in β-cell health is associated with compromised islet-enriched transcription factor (TF) activity that disrupts gene expression programs essential for cell function and identity. TF activity is modulated by recruited coregulators that govern activation and/or repression of target gene expression, thereby providing a supporting layer of control. To date, more than 350 coregulators have been discovered that coordinate nucleosome rearrangements, modify histones, and physically bridge general transcriptional machinery to recruited TFs; however, relatively few have been attributed to β-cell function. Here, we will describe recent findings on those coregulators with direct roles in maintaining islet β-cell health and identity and discuss how disruption of coregulator activity is associated with diabetes pathogenesis.
Successful Microsurgical Replantation of Scalp Amputation Using Medicinal and Chemical Leech Therapy: A Case Report
Authors: Lee Jong Ho , Kim Do Gon , Choi Kang Young , Chung Ho Yun , Lee Joon Seok
Published: November 2020

Scalp amputation is a very rare occurrence worldwide. In particular, replantation failure may occur from venous congestion, which represents a major complication of replantation. Accordingly, this study reports on a scalp amputation case with successful replantation treatment using medicinal and chemical leech therapy. On November 11, 2017, a 47-year-old female patient experienced a complete amputation injury starting from the top of the nose involving the total scalp by rolling machine that packs laundry. Severe venous congestion was controlled by medicinal leech therapy performed six times a day and chemical leech therapy (subcutaneous low-molecular-weight heparin injection) three times a day for 10 days. Approximately 85% of the scalp was replanted, and hair growth was confirmed. The basic concept of replantation surgery, “replace tissue with like tissue,” makes replacement impossible with tissues other than the hair-bearing scalp. Accordingly, the authors present a case of successful replantation with both medicinal and chemical leech therapy.
Problem-Solving or Self-Enhancing? Influences of Diversification and Bright Spot on Corporate Resource Allocation Responses to Performance Shortfalls
Authors: Lim Elizabeth , Audia Pino G.
Published: November 2020

How corporate decision makers respond to firm performance shortfalls has key implications for strategic change in corporate resource allocations. Performance feedback theory assumes problem-solving decision makers faced with performance below aspirations pursue problemistic search and greater strategic change to improve performance. Research on self-enhancement, however, assumes decision makers respond by engaging in lower levels of search and change to portray a favorable self-image. We contribute to advancing this dialogue by investigating contextual features of decision making that prompt self-enhancing behaviors. Specifically, we examine the moderating effects of product and geographic diversification, which reflect indicators of task complexity, and bright spots (defined as the greatest increases in percentage sales of product and geographic segments within a diversified firm’s respective portfolios) on the linkage between performance below aspirations and strategic change. We argue that diversification and bright spots create greater opportunities for corporate decision makers to make self-enhancing interpretations, thereby weakening the relationship between performance below aspirations and strategic change. Empirical tests on Standard & Poor’s 1,500 firms from 1998 to 2006 largely supported the hypotheses.
PEMBELAJARAN ROBOTIK UNTUK MEMPERSIAPKAN GENERASI MUDA MENGHADAPI REVOLUSI INDUSTRI 4.0 DAN SOCIETY 5.0
Authors: Faridawati F Faridawati , Minarto Eko , Istiana Wati Ika , Sutrisno Sutrisno , Hakim Lukman
Published: November 2020

The basic difference between the Industrial revolution 4.0 and society 5.0 is that in the era of the industrial revolution 4.0 technology and computers are used in all human activities, while the era of society 5.0 is an era in which technology becomes a part of humans themselves. The internet is no longer a source of information, but is used to live life. To prepare the young generation to face all the challenges that arise in the era of industrial revolution 4.0 and society 5.0, it is necessary to work hard for educational institutions to educate their students to be ready to face the changing times, and this must start from the most basic level of education, namely at elementary school level (SD and SMP). For this reason, this community service program was arranged, namely improving the quality of education by providing robotic learning training for supervisory teachers and elementary school (SD) students so that they become a generation ready to face all the challenges of the industrial revolution era 4.0 and the society 5.0 era
Both speckle reduction and contrast enhancement for optical coherence tomography via sequential optimization in the logarithmic domain based on a refined Retinex model
Authors: Huang Zongheng , Tang Chen , Xu Min , Shen Yuxin , Lei Zhenkun
Published: November 2020

Optical coherence tomography (OCT) image enhancement is a challenging task because speckle reduction and contrast enhancement need to be addressed simultaneously and effectively. We present a refined Retinex model for guidance in improving the performance of enhancing OCT images accompanied by speckle noise; a physical explanation is provided. Based on this model, we establish two sequential optimization functions in the logarithmic domain for speckle reduction and contrast enhancement, respectively. More specifically, we obtain the despeckled image of an entire OCT image by solving the first optimization function. Incidentally, we can recover the speckle noise map through removing the despeckle component directly. Then, we estimate the illumination and reflectance by solving the second optimization function. Further, we apply the contrast-limited adaptive histogram equalization algorithm to adjust the illumination, and project it back to the reflectance for achieving contrast enhancement. Experimental results demonstrate the robustness and effectiveness of our proposed method. It performs well in both speckle reduction and contrast enhancement and is superior to the other two methods both in terms of qualitative analysis and quantitative assessment. Our method has the practical potential to improve the accuracy of manual screening and computer-aided diagnosis for retinal diseases.