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IntroductionFluorescence in situ hybridization (FISH) is an essential ancillary study used to identify clinically aggressive subsets of large B-cell lymphomas that have MYC, BCL2, or BCL6 rearrangements. Small-volume biopsies such as fine needle aspiration biopsy (FNAB) and core needle biopsy (CNB) are increasingly used to diagnose lymphoma and obtain material for ancillary studies such as FISH. However, the performance of FISH in small biopsies has not been thoroughly evaluated or compared to surgical biopsies.MethodsWe describe the results of MYC, BCL2, and BCL6 FISH in a series of 222 biopsy specimens, including FNAB with cell blocks, CNBs, and surgical excisional or incisional biopsies from 208 unique patients aggregated from 6 academic medical centers. A subset of patients had FNAB followed by a surgical biopsy (either CNB or excisional biopsy) obtained from the same or contiguous anatomic site as part of the same clinical workup; FISH results were compared for these paired specimens.ResultsFISH had a low hybridization failure rate of around 1% across all specimen types. FISH identified concurrent MYC and BCL2 rearrangements in 20 of 197 (10%) specimens and concurrent MYC and BCL6 rearrangements in 3 of 182 (1.6%) specimens. The paired FNAB and surgical biopsy specimens did not show any discrepancies for MYC or BCL2 FISH; of the 17 patients with 34 paired cytology and surgical specimens, only 2 of the 49 FISH probes compared (4% of all comparisons) showed any discrepancy and both were at the BCL6 locus. One discrepancy was due to necrosis of the CNB specimen causing a false negative BCL6 FISH result when compared to the FNAB cell block that demonstrated a BCL6 rearrangement.DiscussionFISH showed a similar hybridization failure rate in all biopsy types. Ultimately, MYC, BCL2, or BCL6 FISH showed 96% concordance when compared across paired cytology and surgical specimens, suggesting FNAB with cell block is equivalent to other biopsy alternatives for evaluation of DLBCL or HGBCL FISH testing.

Rett syndrome is a neurodevelopmental disorder caused by mutations in Mecp2. Here the authors show that Mecp2 loss-of-function leads to upregulation of the NF-κB pathway, and that reducing NF-κB signalling ameliorates phenotypes of Mecp2-null mice, thus offering a potential therapeutic strategy.

Abstract Background Opioid overdoses have continued to increase since the start of the COVID-19 pandemic. The pathways through which the COVID-19 pandemic has affected trajectories of opioid use and opioid-related problems are largely unknown. Using the Epidemic-Pandemic Impacts Inventory (EPII), a novel instrument that assess pandemic-related impacts across multiple life domains, we tested the hypothesis that COVID-related impacts (on e.g., interpersonal conflict, employment, infection exposure, and emotional health) experienced in the early months of the pandemic would predict changes in opioid use and opioid-related problems at follow-up. Methods This analysis was embedded within a cluster randomized type 3 implementation-effectiveness hybrid trial that had enrolled 188 patients across eight opioid treatments prior to the start of the pandemic. Participants had all been recently inducted on medication for opioid use disorder and were actively receiving treatment. Participants reported on their opioid use and opioid-related problems at baseline and 3-, 6-, and 9-month post-baseline assessments. Between May and August 2020, participants were sent an optional invitation to complete the EPII. Results One hundred thirty-three respondents completed the EPII and 129 had sufficient data to analyze the EPII and at least one subsequent follow-up. In logistic and zero-inflated negative binomial analyses adjusting for covariates, each endorsed pandemic impact in the interpersonal conflict domain was associated with 67% increased odds of endorsement of any opioid use, and each impact in the employment and infection exposure-domains was associated with 25% and 75% increases in number of endorsed opioid-related problems, respectively. Conclusions Mitigating the effect of the pandemic on patients’ interpersonal relationships and employment, and promoting greater infection control in opioid treatment programs, could be protective against negative opioid-related outcomes. Trial registration The present study describes secondary data analysis on a previously registered clinical trial: clinicaltrials.gov/ct2/show/NCT03931174.

The financing of innovations is the driving driver of the innovative model of development of any country, and Ukraine in particular. In modern conditions, the importance of venture capital for the economy of Ukraine is growing against the background of reducing alternatives to raising capital for the development of small and high-tech businesses. The reasons for the current state of decline in the innovation and investment process in Ukraine are analyzed and identified. Peculiarities of venture investment in Ukraine are studied. It is determined that the vast majority of venture capital institutions, regardless of their field of activity, are used mainly by large industrial and financial groups to preserve assets and minimize taxation, rather than to finance innovation. The obtained results give grounds for the conclusion that the essence of venture entrepreneurship in Ukraine does not correspond to the American and European models. The current conditions turn venture funds in Ukraine from an instrument of innovative development into a means of making a profit for large financial and industrial groups, which is a hidden reason for slowing down the innovation and investment process. An updated Ukrainian venture model is proposed, taking into account the peculiarities of the economy and a thorough rethinking of the existing structure of venture capital. The introduction of a rational combination of public, private, and research components of the investment process is proposed, i.e. the need to involve universities, scientists, and the scientific elite in the venture industry. It is determined that this model is only one of the components of a comprehensive program to stimulate investment demand, which also includes: ensuring macroeconomic stability; ensuring economic freedom; ensuring economic security; an increase of investment resource; impact on investment propensity; liberalization and development of the financial market; stimulating investment activities through the mechanism of state support for business and science partnerships.

Digital transformation and the rise of Industry 4.0 in times of turbulence are changing the way organizations operate and interact with the people they serve. The massive penetration of network software applications and cloud services forces businesses to digitize their processes and provide innovative products and services. Such mass penetration is changing production and business processes, the labour market, and the basic portrait of the workforce, regardless of industry or role. In addition, we are seeing a shift in the basic skills needed in science, research and development, engineering, IT, management, entrepreneurship, and more. These skills are transformed in accordance with the technological restructuring of productive forces, at the same time, educational activity is characterized by some lag in its development. It is important to realize that the nature and speed of progress dictates the need for an advanced workforce with a multidisciplinary educational background (especially given the number of predictions promising full automation in the next few decades), regardless of industry or function, especially when it comes to deep tech start-ups and high-tech enterprises. It was concluded that in the framework of modern technical evolution, in the conditions of high-tech, and especially deep tech structures, competencies in digital entrepreneurship are, if not key, then very important. The education market is also undergoing changes, but university education is very slow to respond to digital processes. The article proposes a method of assessing the level of competences of students of economic specialties in the field of learning digital entrepreneurship based on soft computing, and also formulates the key basic competencies that arise during the online course of digital entrepreneurship, which are based on the latest development trends in the field of IT. Special considerations for using the model for higher education institutions are discussed. The proposed mathematical model has the property of universality and can be applied to obtain basic statistical samples of the level of competence acquisition based on online courses in various areas of the real sector of the economy.

Background: Despite the utility of parent involvement in continuing care following adolescent residential treatment, parent engagement in traditional office-based treatment is low. In our prior work, we found that parents who had access to a continuing care forum directed questions to a clinical expert and to other parents around five topics: parenting skills; parent support; managing the post-discharge transition; adolescent substance use; family functioning. The current qualitative study elicited questions from parents without access to a continuing care support forum to explore overlapping and new themes Methods: This study was embedded within the pilot trial of a technology-assisted intervention for parents of adolescents in residential treatment for substance use. Thirty-one parents randomized to residential treatment as usual were asked two prompts at follow-up assessments: what questions they would like to ask a clinical expert and what questions they would like to ask other parents of adolescents discharged from residential care. Thematic analysis identified major themes and subthemes Results: Twenty-nine parents generated 208 questions. Analyses revealed three themes identified in prior work: parenting skills; parent support; adolescent substance use. Three new themes emerged: adolescent mental health; treatment needs; socialization Conclusions: The current study identified several distinct needs among parents who did not receive access to a continuing care support forum. Needs identified in this study can inform resources to support parents of adolescents during the post-discharge period. Parents may benefit from convenient access to an experienced clinician for advice on skills and adolescent symptoms, paired with access to parental peer support.

Mathematical modeling and quantitative study of biological motility (in particular, of motility at microscopic scales) is producing new biophysical insight and is offering opportunities for new discoveries at the level of both fundamental science and technology. These range from the explanation of how complex behavior at the level of a single organism emerges from body architecture, to the understanding of collective phenomena in groups of organisms and tissues, and of how these forms of swarm intelligence can be controlled and harnessed in engineering applications, to the elucidation of processes of fundamental biological relevance at the cellular and sub-cellular level. In this paper, some of the most exciting new developments in the fields of locomotion of unicellular organisms, of soft adhesive locomotion across scales, of the study of pore translocation properties of knotted DNA, of the development of synthetic active solid sheets, of the mechanics of the unjamming transition in dense cell collectives, of the mechanics of cell sheet folding in volvocalean algae, and of the self-propulsion of topological defects in active matter are discussed. For each of these topics, we provide a brief state of the art, an example of recent achievements, and some directions for future research.

Identifying meaningful predictors of therapeutic efficacy from preclinical studies is challenging. However, clinical manifestations occurring in both patients and mammalian models offer significant translational value. Many neurological disorders, including inherited, metabolic Niemann–Pick disease, type C (NPC), exhibit ataxia. Both individuals with NPC and murine models manifest ataxia, and investigational therapies impacting this phenotype in mice have been reported to slow disease progression in patients (e.g. miglustat, intrathecal 2-hydroxypropyl-beta-cyclodextrin, and acetyl-L-leucine). Reproducible phenotypic scoring of animal models can facilitate comparisons between genotypes, sexes, disease course, and therapies. Previously, other groups have developed a composite phenotypic scoring system (CPSS), which was subsequently used to distinguish strain-dependent phenotypes and, with modifications, to evaluate potential therapies. However, high inter-rater reliability is paramount to widespread use. We have created a comprehensive, easy-to-follow phenotypic assessment based on the CPSS and have verified its reproducibility using murine models of NPC disease. Application of this scoring system is not limited to NPC disease and may be applicable to other models of neurodegeneration exhibiting motor incoordination, thereby increasing its utility in translational studies.

Introduction: Contingency Management (CM) is one of the most effective interventions for persons with opioid use disorder, but one of the least available interventions in community settings, including opioid treatment programs. Project MIMIC is a NIDA-funded cluster randomized trial that is measuring CM implementation and sustainment across 30 opioid treatment programs in the New England region of the United States. The advent of the COVID-19 pandemic occurred in the midst of Project MIMIC's first cohort of eight opioid treatment programs, presenting a natural opportunity to document and analyze novel challenges to CM sustainment. Utilizing both quantitative and qualitative data collection, we aimed to identify both COVID-related barriers to CM sustainment and innovative workflow strategies to mitigate these barriers. Methods: Quantitative analysis was conducted using data collected from a study-specific CM tracker tool on various CM implementation metrics over three distinct, successive time intervals: prior to COVID-19 social distancing orders with active support; during COVID-19 social distancing orders with active support; and during COVID-19 social distancing orders after removal of support. Semi-structured qualitative interviews were conducted with a representative from each of the eight opioid treatment programs. Using a reflexive team approach, transcripts were coded by independent raters to identify both COVID-related barriers to sustainment and innovative workflow adaptations. Results: Quantitative data revealed a substantial decrease in the number of CM encounters following social distancing orders from 31.8 encounters weekly across eight programs to 6.9 encounters weekly across five programs. A further decline to 1.8 weekly encounters across three programs was observed after implementation support was removed. Four COVID-related barriers were identified via thematic analysis: fear of contagion; difficulty engaging patients remotely; challenges re-defining the CM attendance target due to changing regulations; and staff shortages. Potential adjustments discussed to help address one or more of these barriers included an electronic prize generator; use of technology to promote engagement; brief individual remote check-ins; and expansion of training to non-counseling staff. Conclusion: Although CM implementation challenges emerged during the pandemic, associated workflow adaptations also emerged. The feedback solicited in this study will inform multi-level strategies to aid with CM sustainment post-pandemic.

Our current understanding of exosome signaling among CNS cells is mostly limited to culture models. In this study, authors generated a new cell-type specific exosome reporter mouse line which allows the first in vivo investigation of the localization of neuronal exosomes in the CNS, and also potentially highlights the role of exosomally transferred miR-124-3p in mediating astroglial glutamate uptake function

Стаття присвячена формулюванню концепції інтелектуальної економіки як відповіді на необхідність систематизації і інтеграції існуючого наукового доробку з метою виявлення та пояснення закономірностей функціонування економічних агентів в нових техніко-індустріальних умовах на завершальному етапі трансформаційних перетворень четвертої науково-технічної революції. В результаті дослідження визначено, що ми сьогодні знаходячись наприкінці п’ятої довгої хвилі, одночасно перебуваємо в процесі переходу до шостого техніко-технологічно укладу – неоіндустріального, передумовами трансформації економічної системи в умовах якого є: інкрементальна ентропія техніки і технологій у всі сфери людського життя; завершення четвертої індустріальної (інформаційної) революції; глобалізація; інтелектуальна і технологічна трансформація продуктивних сил, обміну та грошового обігу; трансформація економічних агентів та закономірностей їх взаємодії тощо. А, нова структура вартості, новий ключовий ресурс розвитку, новий тип зв’язку і комунікації, нові суспільні цінності, а також трансформація споживчої поведінки тощо дають підстави заключати про становлення нової економічної системи – інтелектуальної економіки. При цьому вважаємо, що креативна економіка та економіка знань, є складовими частинами інтелектуальної, оскільки є результатом втілення відповідних форм інтелектуального капіталу, а цифрова економіка, трансформувавши постіндустріальне суспільство, стала об’єктивною основою становлення неоіндустріальної ери.

Стаття присвячена дослідженню ролі держави в механізмі сталого розвитку, що дозволило уявити концепцію інноваційної політики, що відповідатиме його засадам. Для обґрунтування теоретико-методологічних засад інноваційної політики держави було досліджене її місце в механізмі сталого розвитку економіки. Визначено, що до сьогодні не існує законодавчого визначення і практичного плану реалізації: було здійснено декілька спроб формулювання і затвердження на законодавчому рівні «Концепції сталого розвитку України», водночас, ці спроби залишились лише у вигляді законопроектів. Офіційного місця в механізмі сталого розвитку нашій державі не передбачено, можемо лише висувати припущення про її роль і напрямки, важелі і способи впливу. За основу прийнято людиноцентричну парадигму сталого розвитку і спроектовано державу, як економічного агента в її імплементації. Роль держави при цьому виявляється у трьох ключових напрямках забезпечення механізму сталого розвитку в межах державної інноваційної політики: нейтралізації загроз, стимулюванні людського і інноваційного розвитку та гарантуванні дотримання національних економічних інтересів. Разом з тим, вважаємо, що політика втручання матиме характеристику інноваційності лише в разі застосування ліберальних регулюючих інструментів.

Abstract Background To determine the root canal morphology of human permanent maxillary and mandibular teeth in a Malaysian subpopulation using cone-beam computed tomography (CBCT). Methods A total of 208 CBCT images were examined retrospectively. Prevalence of an extra root/canal and internal morphology based on Vertucci’s classification were observed in human maxillary and mandibular permanent teeth. Variations in the external and internal morphology were compared in relation to gender and tooth side (left vs right) using Pearson Chi-square and Fisher’s exact tests with significance level set at p

Работа посвящена изучению особенностей застройки и функционального зонирования крупнейших городов российского Заполярья: Апатитов, Воркуты, Мурманска и Норильска. В качестве исходных материалов использованы снимки со спутников SPOT-5 (оптический спектральный диапазон), Landsat 8 (тепловой спектральный диапазон) и генеральные планы изучаемых городов, которые послужили основой для выделения типов застройки. Учёт тепловой структуры городских территорий при анализе их застройки и функционального зонирования позволяет выявить черты городского пространства, не видные на снимках в оптическом диапазоне, важные для оценки благоприятности городской среды для жизни людей.

Effective treatment of invasive lobular carcinoma (ILC) of the breast is hampered by late detection, invasive growth, distant metastasis, and poor response to chemotherapy. Phosphoinositide 3-kinase (PI3K) signaling, one of the major druggable oncogenic signaling networks, is frequently activated in ILC. We investigated treatment response and resistance to AZD8055, an inhibitor of mammalian target of rapamycin (mTOR), in the K14-cre;Cdh1Flox/Flox;Trp53Flox/Flox (KEP) mouse model of metastatic ILC. Inhibition of mTOR signaling blocked the growth of primary KEP tumors as well as the progression of metastatic disease. However, primary tumors and distant metastases eventually acquired resistance after long-term AZD8055 treatment, despite continued effective suppression of mTOR signaling in cancer cells. Interestingly, therapeutic responses were associated with increased expression of genes related to antigen presentation. Consistent with this observation, increased numbers of tumor-infiltrating major histocompatibility complex class II-positive (MHCII+) immune cells were observed in treatment-responsive KEP tumors. Acquisition of treatment resistance was associated with loss of MHCII+ cells and reduced expression of genes related to the adaptive immune system. The therapeutic efficacy of mTOR inhibition was reduced in Rag1−/- mice lacking mature T and B lymphocytes, compared to immunocompetent mice. Furthermore, therapy responsiveness could be partially rescued by transplanting AZD8055-resistant KEP tumors into treatment-naïve immunocompetent hosts. Collectively, these data indicate that the PI3K signaling pathway is an attractive therapeutic target in invasive lobular carcinoma, and that part of the therapeutic effect of mTOR inhibition is mediated by the adaptive immune system.

Advocates for a One Health approach recognize that global health challenges require multidisciplinary collaborative efforts. While past publications have looked at interdisciplinary competency training for collaboration, few have identified the factors and conditions that enable operational One Health. Through a scoping review of the literature, a multidisciplinary team of researchers analyzed peer-reviewed publications describing multisectoral collaborations around infectious disease-related health events. The review identified 12 factors that support successful One Health collaborations and a coordinated response to health events across three levels: two individual factors (education & training and prior experience & existing relationships), four organizational factors (organizational structures, culture, human resources and, communication), and six network factors (network structures, relationships, leadership, management, available & accessible resources, political environment). The researchers also identified the stage of collaboration during which these factors were most critical, further organizing into starting condition or process-based factors. The research found that publications on multisectoral collaboration for health events do not uniformly report on successes or challenges of collaboration and rarely identify outputs or outcomes of the collaborative process. This paper proposes a common language and framework to enable more uniform reporting, implementation, and evaluation of future One Health collaborations.