bluuebunny/crossref_metadata_2025 huggingface dataset:
SABOLICH PROSTHETICS AND RESEARCH: A CONTINUING JOURNEY ON THE ROAD LESS TRAVELED
Authors: Sabolich Scott
Published: September 2021

The Sabolich family had made a unique contribution to both the clinical practice of Prosthetics and Orthotics as well as the business of prosthetics and orthotics. In preparing for this Special Edition, as Co-Editor-in-Chief, I felt it important to include the story of the Sabolich vision for prosthetic clinical practice and their experiences in achieving that vision. Their story is an important part of the history of prosthetic clinical practice in the United States. Their rethinking of what a clinical practice could look like and function as was far-sighted.  Achieving it required both risk taking, as well as a new business model. The reaction from other Prosthetic and Orthotic practitioners was strong. Some saw the new model as visionary while others found it provocative.    The model was based on a concierge style practice, which provided a premium service to a patient from first appointment to providing and maintaining of their device.  They then went further than that by incorporating in-house research into their facility to develop new and innovative prosthetic approaches that would make them leaders in the field of socket design and fit. Their vision was to be a Center of Excellence for Prosthetics and Orthotics Practices, a vison that many people within the sector would likely agree was achieved. I invited current CEO of Scott Sabolich Prosthetics and Research to reflect back on the history of his family’s business and how multiple generations of his family were able to see gaps and create opportunities where others could not see beyond the status quo and even fought hard to maintain the status quo. The evolution of this company provides insight into the successful development of novel business practices and economics in Prosthetics and Orthotics, while staying true to core service principles.  The result was a business model that, in hind sight, had future-proofed the company in the face of the global economic challenges that impacted the sector in 2008-9 and beyond.  It is also an indicator of what opportunities there are, at the business, clinical and technical levels, for those who take the risk of breaking from the status quo. Because of time and capacity constraints on the part of Mr. Scott Sabolich, it was agreed that his professional opinions and insights would be done in an interview format.

Article PDF Link: https://jps.library.utoronto.ca/index.php/cpoj/article/view/37089/28362

How To Cite: Sabolich S. Sabolich Prosthetics and Research: A continuing journey on the road less traveled. Canadian Prosthetics & Orthotics Journal. 2021;Volume 4, Issue 2, No.14. https://doi.org/10.33137/cpoj.v4i2.37089

Corresponding Author: Scott Sabolich, Scott Sabolich Prosthetics and Research, Oklahoma City, USA.E-Mail: scott.sabolich@scottsabolich.comORCID ID: https://orcid.org/0000-0001-5723-7963
Comparison of the Risk of Mortality from Solid Cancers after Radiation Incidents and Occupational Exposures
Authors:   State Research Center – Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency, Moscow, Russian Federation, Koterov A.N. , Ushenkova L.N. ,   State Research Center – Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency, Moscow, Russian Federation, Kalinina M.V. ,   State Research Center – Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency, Moscow, Russian Federation, Biryukov A.P. ,   State Research Center – Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency, Moscow, Russian Federation
Published: September 2021

The purpose of the study was to compare the excess relative risk of mortality (ERR per 1 Sv) from solid cancers during acute — catastrophic or accidental and occupational, fractionated or chronic — exposure. Study materials and methods. Materials of the study: maintained database (source database) on nuclear industry workers from about 40 countries, based on which a pooled analysis of data was conducted to determine the integral value of ERR per 1 Gy for mortality from solid cancers; indicators of cohorts exposed to catastrophic and accidental radiation: the cohort LSS victims of the atomic bombings in Japan; residents of the Techa River — radioactive contamination resulting from releases from "Mayak" production association; Russian liquidators of the Chernobyl nuclear accident. Study results and analysis. Comparison of the ERR of 1 Sv deaths from solid cancers for workers in the global nuclear industry (pooling analysis of data from 37 studies) with those of the LSS cohort; Techa River residents and Chernobyl accident liquidators showed no logical and principled differences, with the risks for the latter two cohorts being the highest. Although the findings partly support the approach of the UN Scientific Committee on the Effects of Atomic Radiation that the carcinogenic effects of acute (catastrophic or accidental) and occupational (fractionated or chronic) radiation exposure are independent of the dose rate factor (DDREF), this issue cannot be considered unequivocally resolved, given the biological mechanisms and radiobiological experimental data. Based on the ERR per 1 Sv, the average external dose, and the annual background cancer mortality rates in Russia and the United States, the expected cancer mortality increase for 100,000 workers in the nuclear industry would be an average of 32-69 people over 10 years — 0.032-0.069% of the group. Such risks, due to multiple carcinogenic non-radiation factors of life and work, as well as fluctuating background values, cannot be taken into account in the practice of disaster medicine and public health.
Radiation Risks of Helicopter Personnel Responding to the Chernobyl Accident: Early and Long-Term Health Disorders
Authors:   State Research Center – Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency, Moscow, Russian Federation, Ushakov I.B. , Fedorov V.P. ,   Voronezh State Institute of Physical Culture, Voronezh, Russian Federation
Published: September 2021

The objectives of the study were to analyze the radiation doses received by helicopter crew members during the work above the emergency unit and the effectiveness of some radioprotective means; to determine the most radiosensitive systems of the body, their condition in the early and distant terms after the accident and the causes of disqualification of flight personnel. Materials and research methods. The first stage of the work was performed directly in the zone of helicopter aviation flight over the Chernobyl NPP emergency power unit. We determined radiation doses received by flight personnel, their dependence on the type of helicopter and pilot's workplace. Also we evaluated the dependence of exposure dose on the radio-protective means used and the primary reaction of pilots to radiation exposure. The second stage of the work was performed on the basis of the Central Research Aviation Hospital and the State Research Test Institute of Military Medicine of the Russian Ministry of Defense. At this stage the results of laboratory, clinical and psychological examination of the pilots who performed the tasks of liquidation of the Chernobyl accident effects in 1986 - 1987 and received regulated radiation doses were assessed. The corresponding medical documents (expert decisions of medical and aviation committees, results of medical follow-up) were studied for the period from 1986 till 2000, i.e. till the time when almost all helicopter liquidators were disqualified for health reasons or discharged due to senior service. Results of the study and their analysis. The radiation doses received by the helicopter crew members during the execution of the assigned tasks over the emergency unit and the efficiency of some radio-protective means were analyzed. The most radiosensitive body systems, their condition in the early and distant terms after the accident and the diseases leading to the disqualification of flight personnel were determined.
Risk-Based Causal Model of Risk Factors for Infection among Medical Personnel Involved in the Care Of Patients with the New COVID-19 Coronavirus Infection
Authors:   State Research Center – Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency, Moscow, Russian Federation, Annenkova E.A. , Tikhonova O.A. ,   State Research Center – Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency, Moscow, Russian Federation, Biryukov A.P. ,   State Research Center – Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency, Moscow, Russian Federation, Baranov L.I. ,   State Research Center – Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency, Moscow, Russian Federation, Dibirgadzhiev I.G. ,   State Research Center – Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency, Moscow, Russian Federation, Sheyanov M.V. ,   State Research Center – Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency, Moscow, Russian Federation, Kasymova O.A. ,   State Research Center – Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency, Moscow, Russian Federation, Parinov O.V. ,   State Research Center – Burnasyan Federal Medical Biophysical Center of Federal Medical Biological Agency, Moscow, Russian Federation
Published: September 2021

The aim of the study is to develop and apply a mathematical model for assessing the risks of contamination of medical personnel involved in providing medical care to patients with COVID-19 in a "red zone" environment. Materials and methods. Based on the analysis of informative signs and information on working conditions in the infectious disease department of the A.I. Burnazyan Federal Medical Biophysical Center of the Federal Medical and Biological Agency of Russia, a decision-making support system was developed to provide an objective assessment of the risks of infection for medical personnel when providing medical care in the "red zone". Results of the study and their analysis. The influence of various risk factors for infection of medical personnel involved in the provision of medical care to patients with new coronavirus infection COVID-19 was analyzed; the most significant risk factors were identified.
Prospects for Creation of Autonomous Life Support Complexes Using Biological Systems for Arctic and Far North Conditions
Authors:   Military innovative technopolis ", Markin I.V. ,   ERA",   , Anapa, Russian Federation, Shchelkanova E.S. ,   Military innovative technopolis "ERA", Anapa, Russian Federation, Volodyashkin R.A. ,   Military innovative technopolis "ERA", Anapa, Russian Federation, Zhurbin E.A. ,   Military innovative technopolis "ERA", Anapa, Russian Federation, Fisun A.Ya. ,   Military innovative technopolis "ERA", Anapa, Russian Federation
Published: September 2021

The purpose of the study is a comparative analysis of the implemented projects of closed ecological systems and the creation on their basis of own scheme of autonomous life-support complex for the conditions of the Arctic and the Far North. Materials and methods of research. The object of the study is implemented projects of closed ecological systems. The subject of the study is the principles of configuration of such projects, their main components and the relationship between them. Research results and their analysis. The support systems created at different times, with the purpose to be used in long-duration space flights or to carry out fundamental ecological research, were analyzed. Such projects were based on the use of biological systems, which opens the possibility of their use to ensure the autonomy of infrastructure in the Arctic and Far North. The scheme of the complex planned for development is proposed. This complex allows to recycle waste products, meets human nutritional needs and produces biofuel of the third generation.
MDV model for planning RT malignant tumors (reference allowance for radiotherapist and medical physicist)
Authors: Klepper L.Ia.
Published: September 2021

Work is dedicated to problem of mathematical modeling and optimization plan RT of the malignancies with the help of created mathematical model, modified distribution Veybull, (the model MDV). The results of the calculation of the best values parameter happen to in work to models MDV for different organ and tissues, received on base systematized clinical data, provided in work Emami et al and Kehwar et al. They allow successfully using the model MDV for planning RT malignancies. Mathematical models is designed on base of the models MDV for reduction non-uniform dose distribution in equivalent on NTCP the uniform irradiation organs and tissues. It Is Shown that these models can be are also used for check of consensus source clinical data.
Issues of establishing an alternative concept of energy development. Part 1. From an increase in the capacity of the power system to an increase in the structural stability of the electric power industry.
Authors: Nekrasov S.A.
Published: September 2021

The monograph presents the Issues of establishing an alternative energy development concept. Based on tectology and systematic economic theory, it is demonstrated that, unlike post-reform increase in quantitative figures of certain energetic companies, the basis for the effectiveness growth of technological chain “production-consumption of energetic resources” as an integral system is the growth of energy development structural sustainability as a result of shifting priority to consumers’ development. Fall of tariffs for electric power is possible due to consumers’ development, but without any damage to them, as well as increase in energy supply reliability and current energetic system figures, and prospectively – even its integration with renewable sources with minimal expenses. For university teachers, researchers, consultants and experts in the energy sector, graduate students and undergraduates.
Mathematical Modeling and Forecast of the “First Wave” of COVID-19 in Russia
Authors:   CEMI Russian Academy of Sciences, Arutyunov A.L.
Published: September 2021

The article presents the results of a study on mathematical modeling of the spread of a new type of coronavirus disease codenamed (according to the WHO classification) “COVID-19».
Fontana K.A. Governing Water and Energy as Specific Resourses
Authors:   CEMI RAS, Yerznkyan B.H. , Fontana K.A. ,   CEMI RAS
Published: September 2021

Water and energy are resources without which it is impossible to present, at least, neither functioning of industrial enterprises nor existence of housekeeping. In terms of Oliver Williamson they are the typical resources (assets) of the general setting. Cases are at the same time possible, when they come forward as resources, alternative to generally accepted, namely: they appear in a role of specific resources. Reasons for it can be various, depending on the specificity of the concrete situation. As in the case of specific resources (assets) risks are great, it causes the special system requirements management such by water and energy. This paper is devoted to the exposure of features of these requirements.
Uncertainty and Risk Phenomenon in the Enterprise Managing
Authors:   CEMI RAS, Kachalov R.M. , Kurshina F.L. ,   CEMI RAS, Pletenenko O.A. ,   CEMI RAS
Published: September 2021

Periods of aggravation of the situation in the economy and politics, especially in connection with the crisis and transformation processes in society, are usually accompanied by increased interest in the problem of the phenomenon of risk and uncertainty in the economy. In this regard, the main results of creating methodological support and its practical application for solving management problems of modern production enterprises are analyzed. It is taken into account that management decisions are developed and implemented in an uncertain future state of the management object, as well as incomplete information about the past and current state of the surrounding socio-economic environment. Since in this case it is impossible to estimate in advance possible hindrances and obstacles to the «movement» of the controlled object to the goal and ways to overcome them, modern economic science has introduced the concept of «the phenomenon of economic risk» to solve this problem. It is proved that with the help of this concept and its applied characteristics, it is possible to analyze the purposeful activity of the control object and develop ways to control it when moving towards the goal in conditions of uncertainty. The main operational characteristics and variables of the risk management subsystem are analyzed, as well as applied methods for implementing risk management procedures in modern enterprises. It is shown that to reduce the economic risk level in the activities of enterprises, first of all, it is necessary to draw attention to the problem of forming a specific culture of risk management within economic organizations, which will allow using the advantages and positive features of such a culture to improve the efficiency of enterprises, including in the conditions of digitalization of the general economic space. The hypothesis is introduced that the inevitable spread of risk management in the practice of modern and especially promising enterprises as economic managed objects should be based, including on the application of the achievements of behavioral economic theory.
The Place of Visualization of Economic Benefits in the Ratio of Spiritual and Material Consumption
Authors:   THE STATE UNIVERSITY OF MANAGEMENT, Bykovskaya E.N. , Isaenko V.O. , Rybina M.N. ,   THE STATE UNIVERSITY OF MANAGEMENT
Published: September 2021

A special characteristic of the modern economy is the transition to a new type of consumption. In this regard, the question of the economics of creative consumption and individualized consumption is clearly raised; consumption is becoming an increasingly significant factor in human development. Obtaining a new quality of everyday life is possible due to many factors of socio-economic, political, environmental nature. However, without attention to intangible assets, in particular the visualization of objects and phenomena, it is not possible to obtain a new quality of everyday life. Visualization of objects and phenomena has a number of socio-economic functions that not only ensure competitiveness for economic benefits, but also become a bond of spiritual and material consumption in the daily life of the modern human being. However, this understanding of the problem remains debatable, so the relevance of its appeal is not in doubt
A Role of Digitalization in Decision of Problem of Increase of Tie-Up of Territories of Russian Federation
Authors:   CEMI Russian Academy of Sciences, Jiltsova E.S.
Published: September 2021

In the paper, the questions of influence of disjoined of regions of Russian Federation and their transport availability are examined on the terms of life and economic activity, measures undertaken be the Government and by regional authorities for the increase of tie-up of separate regions of Russia by means of transport and of communication networks, and also role of digitalization in the decision of problem of tie-up of territories are analyzed
Production and Technological Potential of the Enterprise
Authors:   CEMI Russian Academy of Sciences, Zotov V.V. , Petukhova O.V. ,   CEMI Russian Academy of Sciences, Presnyakov V.F. ,   CEMI Russian Academy of Sciences
Published: September 2021

The article offers an approach to the analysis of the structure and subsequent assessment of the production and technological potential of the enterprise, which is based on the rejection of the position that the concept of potential includes all the resources that are involved in the production process, become its factors. It is proposed to consider the potential as the state of an enterprise that characterizes its ability to perform the roles of an enterprise as a production system, as an economic entity, and as a system of collective action. To identify the information components of the enterprise's potential, the concept of system aspects of the enterprise's functioning is introduced, which is based on the fact of its involvement in the life of society as a larger social whole. The objects of such analysis include ethical, informational, economic, industrial, personnel, spatial and social aspects – all those in which people's interactions are characterized by conflicts of interests. Performance characteristics of system requirements are parameters of the state of the enterprise, which serve to describe the ability of the enterprise to perform its functions in the relevant aspects. To characterize the measurement of changes in the value of indicators, it is proposed to use indicators that reflect the use of certain methods to achieve their values. Such indicators should be included in the indicators of internal statistical accounting at the enterprise. The article offers a unified terminological system of indicators used to assess the production and technological potential of an enterprise, including indicators of the production function, marketing and organization of production-functions that are associated with the formation of the production and technological potential of the enterprise.
Institutional Aspects of Russian Economic Thought: A View From Outside
Authors:   CEMI Russian Academy of Sciences, Yerznkyan B.H.
Published: September 2021

The institutional aspects of the Russian economic thought as they are seen to the professor from Montenegro Veselin Draskovic in comparison with such aspects of economic thougt of the former socialistic countries, including Montenegro and wider – former Yugoslavia are studied. The special attention is spared to illumination of the representative themes and directions of the development of economic thougt – both accepted and declined by Russian practice and official politics. The most essential problems and taking place theoretical discussions, lasting during all period of socialism with an accent on today's realities, are investigated. Undertaken by the author of book the comparative institutional analysis of consequences of the strict government control in different periods of development of economic thought allows to differentiate two most essential factors of influence – domination of politics over all forms of life, from one side, and cult of personality – from another. Particular interest is presented by the selfguided enterprises, as they can be interpreted as the popular now ecosystems, i.e. ecosystems in miniature.
Induced Breeding of Fresh Water Menoda Catfish (Hemibagrus Menoda) Using Ovupin Hormone
Authors: Islam N , Islam MF , Islam MS , Miah MI
Published: September 2021

An experiment on induced breeding of menoda catfish, Hemibagrus menoda was conducted during the period from May 2017 to July 2018 by using commercial Ovupin hormone (GnRHa, Gonadotropin Releasing Hormone Analogues) to attain its optimum dose. The study consists of three treatments, each with three replications. The objective of the experiment was to find out the effective dose for induced breeding. The breeding parameters were determined in terms of ovulation, fertilization, hatching, and survival rate. A total of 36 males and 18 females lived brood fish were kept in the ratio of 2♂:1♀ for breeding purpose. The commercial Ovupin hormone were injected at the doses of 4 (T1), 6 (T2), 7 (T3) mL Ovupin·kg-1body weight for female and 1.5(T1), 2 (T2), 3(T3) mL Ovupin·kg-1 body weight for male in a triplicate replication. In this study, it was found that treatment T2 demonstrated the best spawning performance for both male and female and were statistically significant (p<0.05). The investigation indicated that the dose of Ovupin hormone 6mL Ovupin·kg-1body weight for female and 2 mL Ovupin·kg-1 body weight for male determines the highest spawning performance of menoda catfish which should be recommended for high quality eggs and larvae.
J. Biodivers. Conserv. Bioresour. Manag. 2020, 6(2): 11-18
PENILAIAN KINERJA KARYAWAN MENGGUNAKAN METODE TOPSIS
Authors: Sukamto Sukamto , Andriyani Yanti , Wahyuni Kiki
Published: September 2021

Abstract: The Employee’s performance appraisal is something that must be done by the company or organization to be able to evaluate the company's development. Permata Hati Duri Hospital conducts employee performance appraisals every month. This study aims to create an employee performance appraisal system that can facilitate the hospital when evaluating employee performance. The assessment criteria used are competence, professionalism, communication, management and friendliness with. This research uses TOPSIS method, PHP and MySQL programming as database. The sample used is 10 employees. The final result obtained in the system is the result of ranking employee.            Keywords: employee performance appraisal; topsis.  Abstrak: Penilaian kinerja karyawan adalah hal yang harus dilakukan oleh perusahaan atau organisasi untuk dapat mengevaluasi perkembangan perusahaan. Rumah Sakit Permata Hati Duri melakukan penilaian kinerja terhadap karyawan pada setiap bulannya. Penelitian ini bertujuan membuat sistem penilaian kinerja karyawan yang dapat memudahkan pihak rumah sakit saat melakukan penilaian kinerja karyawan. Kriteria penilaian yang digunakan adalah kompetensi, profesionalisme, komunikasi, manajemen dan keramahan dengan. Penelitian ini menggunakan metode TOPSIS, pemograman PHP dan MySQL sebagai database. Adapun sampel yang digunakan adalah 10 karyawan. Hasil akhir yang didapatkan pada sistem berupa hasil perangkingan nilai karyawan. Kata kunci: penilaian kinerja karyawan; topsis.
Temporal trends in home-grown forage eaten on New Zealand dairy farms
Authors: Mills Ryan , Neal Mark
Published: September 2021

Pasture is the main source of feed on New Zealand dairy farms, having the benefit of a low cost of production, giving New Zealand’s dairy industry a competitive cost advantage in international markets. Previous literature indicates a plateau in forage grown and consumed on farm (referred to as pasture and crop eaten) over the last 20 years. Farm-level performance data over 14 years from DairyBase across Northland, Waikato, Canterbury and Otago were used to analyse the medium-term trends of pasture and crop eaten at the middle (median) and top (frontier) portions of the distributions of pasture and crop eaten. A performance metric was designed to compare the time trends between top-, average- and bottom-performing farms at the national level. The results were consistent with prior literature with no substantial evidence of an increasing trend in pasture and crop eaten across any region. Furthermore, the results showed that at a national level, top-performing farms were not improving on their pasture and crop eaten, while the average- and bottom-performing farms are improving slightly. The lack of a consistent positive trend is concerning for the dairy sector’s international competitiveness, making further research into new pastoral technologies and techniques paramount for maintaining New Zealand’s competitive position.
Interaktioner och relationer mellan lärare och elever, en kort översikt
Authors: Wubbels Theo
Published: September 2021

Positiva relationer mellan lärare och elever är av största vikt för elevers lärande (se t ex Wubbels, et al., 2016). Lärare som har positiva relationer med sina elever sägs ofta ha “varma krav”, det vill säga de visar omsorg om sina elever samtidigt som de också ställer höga krav på dem (Ross et al., 2008). Sådana lärar-elev-relationer (ett ganska stabilt, generellt beteende, eftersom det är konstant över en längre tid) byggs upp genom interaktioner mellan läraren och eleverna (det beteende som elever och lärare uppvisar från en stund till nästa), särskilt under det första mötet mellan läraren och en ny klass (Mainhard et al., 2011).
Metabolic Biomarkers for the Early Detection of Cancer Cachexia
Authors: O’Connell Thomas M. , Golzarri-Arroyo Lilian , Pin Fabrizio , Barreto Rafael , Dickinson Stephanie L. , Couch Marion E. , Bonetto Andrea
Published: September 2021

Background:Cancer cachexia is a severe metabolic disorder characterized by progressive weight loss along with a dramatic loss in skeletal muscle and adipose tissue. Like cancer, cachexia progresses in stages starting with pre-cachexia to cachexia and finally to refractory cachexia. In the refractory stage, patients are no longer responsive to therapy and management of weight loss is no longer possible. It is therefore critical to detect cachexia as early as possible. In this study we applied a metabolomics approach to search for early biomarkers of cachexia.

Methods:Multi-platform metabolomics analyses were applied to the murine Colon-26 (C26) model of cachexia. Tumor bearing mice (n= 5) were sacrificed every other day over the 14-day time course and control mice (n= 5) were sacrificed every fourth day starting at day 2. Linear regression modeling of the data yielded metabolic trajectories that were compared with the trajectories of body weight and skeletal muscle loss to look for early biomarkers of cachexia.

Results:Weight loss in the tumor-bearing mice became significant at day 9 as did the loss of tibialis muscle. The loss of muscle in the gastrocnemius and quadriceps was significant at day 7. Reductions in amino acids were among the earliest metabolic biomarkers of cachexia. The earliest change was in methionine at day 4. Significant alterations in acylcarnitines and lipoproteins were also detected several days prior to weight loss.

Conclusion:The results of this study demonstrate that metabolic alterations appear well in advance of observable weight loss. The earliest and most significant alterations were found in amino acids and lipoproteins. Validation of these results in other models of cachexia and in clinical studies will pave the way for a clinical diagnostic panel for the early detection of cachexia. Such a panel would provide a tremendous advance in cachectic patient management and in the design of clinical trials for new therapeutic interventions.
Classification of Estrogen Receptor-Positive Breast Cancer Based on Immunogenomic Profiling and Validation at Single-Cell Resolution
Authors: Ma Xianxiong , Chen Hengyu , Yang Ming , Ke Zunxiang , Wang Mengyi , Huang Tao , Li Lei
Published: September 2021

Background: The aim of this paper was to identify an immunotherapy-sensitive subtype for estrogen receptor-positive breast cancer (ER+ BC) patients by exploring the relationship between cancer genetic programs and antitumor immunity via multidimensional genome-scale analyses.

Methods: Multidimensional ER+ BC high-throughput data (raw count data) including gene expression profiles, copy number variation (CNV) data, single-nucleotide polymorphism mutation data, and relevant clinical information were downloaded from The Cancer Genome Atlas to explore an immune subtype sensitive to immunotherapy using the Consensus Cluster Plus algorithm based on multidimensional genome-scale analyses. One ArrayExpress dataset and eight Gene Expression Omnibus (GEO) datasets (GEO-meta dataset) as well as the Molecular Taxonomy of Breast Cancer International Consortium dataset were used as validation sets to confirm the findings regarding the immune profiles, mutational features, and survival outcomes of the three identified immune subtypes. Moreover, the development trajectory of ER+ BC patients from the single-cell resolution level was also explored.

Results: Through comprehensive bioinformatics analysis, three immune subtypes of ER+ BC (C1, C2, and C3, designated the immune suppressive, activation, and neutral subtypes, respectively) were identified. C2 was associated with up-regulated immune cell signatures and immune checkpoint genes. Additionally, five tumor-related pathways (transforming growth factor, epithelial–mesenchymal transition, extracellular matrix, interferon-γ, and WNT signaling) tended to be more activated in C2 than in C1 and C3. Moreover, C2 was associated with a lower tumor mutation burden, a decreased neoantigen load, and fewer CNVs. Drug sensitivity analysis further showed that C2 may be more sensitive to immunosuppressive agents.

Conclusion: C2 (the immune activation subtype) may be sensitive to immunotherapy, which provides new insights into effective treatment approaches for ER+ BC.
Identification of N6-Methyladenosine-Associated Long Non-coding RNAs for Immunotherapeutic Response and Prognosis in Patients With Pancreatic Cancer
Authors: Yu Xinshuang , Dong Peng , Yan Yu , Liu Fengjun , Wang Hui , Lv Yajuan , Song Meijuan , Yao Qingqiang , Hu Sanyuan
Published: September 2021

Pancreatic cancer is a highly aggressive disease with poor prognosis. N6-methyladenosine (m6A) is critical for post-transcriptional modification of messenger RNA (mRNA) and long non-coding RNA (lncRNA). However, the m6A-associated lncRNAs (m6A-lncRNA) and their values in predicting clinical outcomes and immune microenvironmental status in pancreatic cancer patients remain largely unexplored. This study aimed to evaluate the importance of m6A-lncRNA and established a m6A-lncRNA signature for predicting immunotherapeutic response and prognosis of pancreatic cancer. The m6A-lncRNA co-expression networks were constructed using data from the TCGA and GTEx database. Based on the least absolute shrinkage and selection operator (LASSO) analysis, we constructed an 8 m6A-lncRNA signature risk model, and selection operator (LASSO) analysis, and stratified patients into the high- and low-risk groups with significant difference in overall survival (OS) (HR = 2.68, 95% CI = 1.74–4.14, P < 0.0001). Patients in the high-risk group showed significantly reduced OS compared to patients in the low-risk group (P < 0.001). The clinical characteristics and m6A-lncRNA risk scores were used to construct a nomogram which accurately predicted the OS in pancreatic cancer. TIMER 2.0 were used to investigate tumor immune infiltrating cells and its relationship with pancreatic cancer. CIBERSORT analysis revealed increased higher infiltration proportions of M0 and M2 macrophages, and lower infiltration of naive B cell, CD8+ T cell and Treg cells in the high-risk group. Compared to the low-risk group, functional annotation using ssGSEA showed that T cell infiltration and the differential immune-related check-point genes are expressed at low level in the high-risk group (P < 0.05). In summary, our study constructed a novel m6A-associated lncRNAs signature to predict immunotherapeutic responses and provided a novel nomogram for the prognosis prediction of pancreatic cancer.
Constitutive TRIM22 Expression in the Respiratory Tract Confers a Pre-Existing Defence Against Influenza A Virus Infection
Authors: Charman Matthew , McFarlane Steven , Wojtus Joanna K. , Sloan Elizabeth , Dewar Rebecca , Leeming Gail , Al-Saadi Mohammed , Hunter Laura , Carroll Miles W. , Stewart James P. , Digard Paul , Hutchinson Edward , Boutell Chris
Published: September 2021

The induction of antiviral effector proteins as part of a homeostatically controlled innate immune response to infection plays a critical role in limiting the propagation and transmission of respiratory pathogens. However, the prolonged induction of this immune response can lead to lung hyperinflammation, tissue damage, and respiratory failure. We hypothesized that tissues exposed to the constant threat of infection may constitutively express higher levels of antiviral effector proteins to reduce the need to activate potentially harmful innate immune defences. By analysing transcriptomic data derived from a range of human tissues, we identify lung tissue to express constitutively higher levels of antiviral effector genes relative to that of other mucosal and non-mucosal tissues. By using primary cell lines and the airways of rhesus macaques, we show the interferon-stimulated antiviral effector protein TRIM22 (TRIpartite Motif 22) to be constitutively expressed in the lung independently of viral infection or innate immune stimulation. These findings contrast with previous reports that have shown TRIM22 expression in laboratory-adapted cell lines to require interferon stimulation. We demonstrate that constitutive levels of TRIM22 are sufficient to inhibit the onset of human and avian influenza A virus (IAV) infection by restricting the onset of viral transcription independently of interferon-mediated innate immune defences. Thus, we identify TRIM22 to confer a pre-existing (intrinsic) intracellular defence against IAV infection in cells derived from the respiratory tract. Our data highlight the importance of tissue-specific and cell-type dependent patterns of pre-existing immune gene expression in the intracellular restriction of IAV from the outset of infection.
Strategies for Rapid Identification of Acinetobacter baumannii Membrane Proteins and Polymyxin B’s Effects
Authors: Lu Yun , Hu Xinxin , Nie Tongying , Yang Xinyi , Li Congran , You Xuefu
Published: September 2021

Acinetobacter baumannii, especially multidrug resistant Acinetobacter baumannii, is a notable source of pressure in the areas of public health and antibiotic development. To overcome this problem, attention has been focused on membrane proteins. Different digestion methods and extraction detergents were examined for membrane proteome sample preparation, and label-free quantitative and targeted proteome analyses of the polymyxin B-induced Acinetobacter baumannii ATCC 19606 membrane proteome were performed based on nano LC-MS/MS. Ultracentrifugation of proteins at a speed of 150,000×g, digestion by trypsin, filter-aided sample preparation, and detergents such as lauryldimethylamine-N-oxide were proved as a fast and effective way for identification of membrane proteome by nano LC-MS/MS. Upon treatment with polymyxin B, expression levels of 15 proteins related to membrane structure, transporters, cell surface, and periplasmic space were found to be significantly changed. Furthermore, targeted proteome was also used to confirm these changes. A relatively rapid membrane proteome preparation method was developed, and a more comprehensive view of changes in the Acinetobacter baumannii membrane proteome under polymyxin B pressure was obtained.
Using a Conflict Framework Analysis to Help Beekeepers and Giant Armadillos (Priodontes maximus) Coexist
Authors: Catapani Mariana L. , Morsello Carla , Oliveira Bruna , Desbiez Arnaud L. J.
Published: September 2021

Damage caused by wildlife is one reason preventing peaceful coexistence between humans and wildlife. To identify the complexity and scope of human-wildlife interactions and to guide conservation interventions, a theoretical framework has been recently proposed, based on the field of conflict analysis and peacebuilding. Despite its importance, to our knowledge, there are no studies yet testing the framework. We therefore adapted and expanded the framework to investigate a wildlife-people interaction scenario, involving damage by giant armadillos (Priodontes maximus) to apiaries in the Brazilian Cerrado biome of Mato Grosso do Sul state. From August to November 2018, we interviewed 111 beekeepers identified through a mixed random and snowball sampling design to assess at which level of conflict this interaction could be framed, and to identify strategies able to promote coexistence. Analysis of the five key areas of the framework suggested the current human-wildlife interaction is a level one conflict. This means the negative relation between beekeepers and giant armadillos is still not rooted in less visible, more complex social disagreements, but founded in a material dispute: destruction of beehives. We used the findings to create an intervention strategy which involves: (i) the implementation of mitigation strategies that prevent giant armadillos from predating beehives; (ii) a certification scheme to acknowledge beekeepers' efforts to implement the mitigation strategies, and (iii) a Citizen Science Program using an app that enables data gathering for adaptive management, as well as maintains beekeeper engagement. We hope beekeepers-giant armadillos' coexistence will become beneficial rather than a challenge with the novel interventions.
Early Second Language Learners, Staff Responsiveness and Child Engagement in the Swedish Preschool Context in Relation to Child Behaviour Characteristics and Staffing
Authors: Finnman Johannes , Danielsson Henrik , Sjöman Madeleine , Granlund Mats , Almqvist Lena
Published: September 2021

Preschool staffs' responsiveness affects children’s behaviour, their difficulties, and engagement in the preschool context, but children’s behaviour and characteristics also affect staff responsiveness. Early second language learners (L2-learners) have been shown to have more problems with behaviour and emotions and lower engagement in preschool. Being engaged in preschool activities predicts future academic performance, attitude towards school and well-being in the short and long term, and can be promoted by the preschool staff. Knowledge of which factors support engagement in preschool for L2-learners can help prevent, in the early years, negative pathways based on low engagement and problems with behaviour and emotions. This cross-sectional study used data from a longitudinal study to investigate the relationship between child engagement and staff responsiveness as well as how child age, child problems with behaviour and emotions, child group size, and the child:staff ratio impact child engagement and staff responsiveness. The study also investigated whether these relations differ between L2-learners and children learning Swedish as their first language (L1-learners). Preschool staff (N = 611) reported through questionnaires on engagement, age, problems with behaviour and emotions and emotional symptoms of 832 children aged 13–71 months, as well as on staffing and staff responsiveness. With a path analysis extended by multi-group analysis, we found two models suggesting that age, problems with behaviour and emotions and preschool staff responsiveness influence child engagement, irrespective of background. The study also found that child engagement significantly influenced staff responsiveness. The multi-group analysis only weakly supported the hypothesis that the child’s age affects staff responsiveness more strongly for L2-learners. The results indicate that individual children and child groups themselves can affect the responsiveness of their staff, and that children with low engagement risk being neglected. L2-learners are at increased risk since they tend to display lower engagement and more behaviour problems in preschool in general. If not attended to early, the lower engagement already apparent among L2-learners in preschool can create stable patterns of low engagement and problems with behaviour and emotions that extend beyond the preschool years and having negative effects on the children’s later well-being and school performance.
Sex Dimorphic Associations of Gestational Diabetes Mellitus With Cord Plasma Fatty Acid Binding Protein 4 and Estradiol
Authors: Liu Xin , Zheng Tao , Xu Ya-Jie , Yang Meng-Nan , Wang Wen-Juan , Huang Rong , Zhang Guang-Hui , Guo Yu-Na , Zhang Jun , Ouyang Fengxiu , Li Fei , Luo Zhong-Cheng
Published: September 2021

Fatty acid binding protein 4 (FABP4) has been associated with insulin resistance. Gestational diabetes mellitus (GDM) impairs fetal insulin sensitivity. Female newborns are more insulin resistant than male newborns. We sought to evaluate the association between GDM and cord blood FABP4, and explore potential sex dimorphic associations and the roles of sex hormones. This was a nested case-control study in the Shanghai Birth Cohort, including 153 pairs of newborns in GDM vs. euglycemic pregnancies matched by infant sex and gestational age at delivery. Cord plasma FABP4, leptin, total and high-molecular-weight adiponectin, testosterone and estradiol concentrations were measured. Adjusting for maternal and neonatal characteristics, cord plasma FABP4 (Mean ± SD: 27.0 ± 19.6 vs. 18.8 ± 9.6 ng/mL, P=0.045) and estradiol (52.0 ± 28.6 vs. 44.2 ± 26.6, ng/mL, P=0.005) concentrations were higher comparing GDM vs. euglycemic pregnancies in males, but similar in females (all P>0.5). Mediation analyses showed that the positive association between GDM and cord plasma FABP4 in males could be partly mediated by estradiol (P=0.03), but not by testosterone (P=0.72). Cord plasma FABP4 was positively correlated with total adiponectin in females (r=0.17, P=0.053), but the correlation was in the opposite direction in males (r=-0.11, P=0.16) (test for difference in r, P=0.02). Cord plasma FABP4 was not correlated with leptin in both sexes. The study is the first to demonstrate sex-dimorphic associations between GDM and cord plasma FABP4 or estradiol, and between FABP4 and adiponectin in newborns. GDM may affect fetal circulating FABP4 and estradiol levels in males only.
Development and Validation of a Gene Mutation-Associated Nomogram for Hepatocellular Carcinoma Patients From Four Countries
Authors: Huang Tingping , Yan Tao , Chen Gonghai , Zhang Chunqing
Published: September 2021

Background: Genomic alteration is the basis of occurrence and development of carcinoma. Specific gene mutation may be associated with the prognosis of hepatocellular carcinoma (HCC) patients without distant or lymphatic metastases. Hence, we developed a nomogram based on prognostic gene mutations that could predict the overall survival of HCC patients at early stage and provide reference for immunotherapy.

Methods: HCC cohorts were obtained from The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. The total patient was randomly assigned to training and validation sets. Univariate and multivariate cox analysis were used to select significant variables for construction of nomogram. The support vector machine (SVM) and principal component analysis (PCA) were used to assess the distinguished effect of significant genes. Besides, the nomogram model was evaluated by concordance index, time-dependent receiver operating characteristics (ROC) curve, calibration curve and decision curve analysis (DCA). Gene Set Enrichment Analysis (GSEA), CIBERSORT, Tumor Immune Dysfunction and Exclusion (TIDE) and Immunophenoscore (IPS) were utilized to explore the potential mechanism of immune-related process and immunotherapy.

Results: A total of 695 HCC patients were selected in the process including 495 training patients and 200 validation patients. Nomogram was constructed based on T stage, age, country, mutation status of DOCK2, EYS, MACF1 and TP53. The assessment showed the nomogram has good discrimination and high consistence between predicted and actual data. Furthermore, we found T cell exclusion was the potential mechanism of malignant progression in high-risk group. Meanwhile, low-risk group might be sensitive to immunotherapy and benefit from CTLA-4 blocker treatment.

Conclusion: Our research established a nomogram based on mutant genes and clinical parameters, and revealed the underlying association between these risk factors and immune-related process.