bluuebunny/crossref_metadata_2025 huggingface dataset:
Loss of the neurodevelopmental disease-associated gene miR-146a impairs neural progenitor differentiation and causes learning and memory deficits
Authors: Fregeac Julien , Moriceau Stéphanie , Poli Antoine , Nguyen Lam Son , Oury Franck , Colleaux Laurence
Published: March 2020

Background

Formation and maintenance of appropriate neural networks require tight regulation of neural stem cell proliferation, differentiation, and neurogenesis. microRNAs (miRNAs) play an important role in brain development and plasticity, and dysregulated miRNA profiles have been linked to neurodevelopmental disorders including autism, schizophrenia, or intellectual disability. Yet, the functional role of miRNAs in neural development and postnatal brain functions remains unclear.

Methods

Using a combination of cell biology techniques as well as behavioral studies and brain imaging, we characterize mouse models with either constitutive inactivation or selectively hippocampal knockdown of the neurodevelopmental disease-associated gene Mir146a, the most commonly deregulated miRNA in developmental brain disorders (DBD).

Results

We first show that during development, loss ofmiR-146aimpairs the differentiation of radial glial cells, neurogenesis process, and neurite extension. In the mouse adult brain, loss ofmiR-146acorrelates with an increased hippocampal asymmetry coupled with defects in spatial learning and memory performances. Moreover, selective hippocampal downregulation ofmiR-146ain adult mice causes severe hippocampal-dependent memory impairments indicating for the first time a role for this miRNA in postnatal brain functions.

Conclusion

Our results show thatmiR-146aexpression is critical for correct differentiation of neural stem cell during brain development and provide for the first time a strong argument for a postnatal role ofmiR-146ain regulating hippocampal-dependent memory. Furthermore, the demonstration that theMir146a−/−mouse recapitulates several aspects reported in DBD patients, including impaired neurogenesis, abnormal brain anatomy, and working and spatial memories deficits, provides convincing evidence that the dysregulation ofmiR146acontributes to the pathogenesis of DBDs.
CCR5-Δ32 biology, gene editing, and warnings for the future of CRISPR-Cas9 as a human and humane gene editing tool
Authors: Xu MengMeng
Published: March 2020

Background

Biomedical technologies have not just improved human health but also assisted in the creation of human life. Since the first birth of a healthy baby by in vitro fertilization (IVF) 40 years ago, IVF has been the mainstay treatment for couples struggling with infertility. This technology, in addition to increasingly accessible genetic testing, has made it possible for countless couples to have children. Since CRISPR-Cas9 gene editing was described in 2015, its potential for targeting genetic diseases has been much anticipated. However, the potential of using CRISPR-Cas9 for human germline modification has led to many fears of “designer babies” and widespread concerns for the impact of this technology on human evolution and its implications in Social Darwinism. In addition to these ethical/moral concerns, there remain many unknowns about CRISPR-Cas9 technology and endless unanticipated consequence to gene editing.

Methods

In this paper, we analyze the current progresses of CRISPR-Cas9 technology and discuss the theoretical advantages of certain allelic variances in the C-C chemokine receptor 5 gene (CCR5) in the setting of recent ethical/moral concerns regarding gene editing using the CRISPR-Cas9 system.

Results

These uncertainties have been highlighted recently by the birth of Chinese twins whose C-C chemokine receptor 5 (CCR5) gene had been inactivated via CRISPR-Cas9 to be theoretically protective against HIV infection. CCR5 signaling is critical for the successful infection of human immunodeficiency virus (HIV) and people with homozygous inactivating CCR5-Δ32 mutations have been shown to be protected against HIV infection. Those with the CCR5-Δ32/Δ32 mutation also have greater neuroplasticity, allowing for improved recovery from neurological trauma, and decreased Chagas cardiomyopathy. However, the CCR5-Δ32/Δ32 mutation has also been associated with earlier clinical manifestations for West Nile infection, ambiguous effects on osteoclast function, and a four-fold increased mortality from influenza infection. These detrimental health impacts, in addition to the confounding factor that these CRISPR babies do not carry this exact CCR5-Δ32/Δ32 mutation, lead to many questions regarding the children’s future health and the moral conundrum of their birth. The creation and birth of these babies was not completed with any scientific, ethical, or governmental oversight, which has spurned the acceleration of talks regarding global regulations for human genetic editing.

Conclusions

Although we can try to regulate for ethical, health-related only use of this technology, moral and governmental oversights need to be supplemented by technical regulations. For instance, whole genome sequencing needs to be used to eliminate off-target mutations that could affect the health and safety of infants born to this process. Like Pandora’s Box, we cannot pretend to forget CRISPR-Cas9 technology, all we can do is ensure a safe, moral, and equitable used of this technology.
BRCA1 and homologous recombination: implications from mouse embryonic development
Authors: Liu Yidan , Lu Lin-Yu
Published: March 2020

As an important player in DNA damage response, BRCA1 maintains genomic stability and suppresses tumorigenesis by promoting DNA double-strand break (DSB) repair through homologous recombination (HR). Since the cloning of BRCA1 gene, many Brca1 mutant alleles have been generated in mice. Mice carrying homozygous Brca1 mutant alleles are embryonic lethal, suggesting that BRCA1’s functions are important for embryonic development. Studies of embryonic development in Brca1 mutant mice not only reveal the physiological significance of BRCA1’s known function in HR, but also lead to the discovery of BRCA1’s new function in HR: regulation of DSB repair pathway choice.
New insights into the cellular activities of Fndc5/Irisin and its signaling pathways
Authors: Rabiee Farzaneh , Lachinani Liana , Ghaedi Sarvenaz , Nasr-Esfahani Mohammad Hossein , Megraw Timothy L. , Ghaedi Kamran
Published: March 2020

Fndc5, a well-defined myokine and also identified as an adipokine, has a critical role in modulation of metabolism and protection against obesity. These important functions are mediated by irisin, a secretory peptide produced from proteolytic processing of Fndc5. The other beneficial physiological effects of irisin are alleviation of oxidative stress, neuroprotective effects, and anti-inflammatory properties and associated anti-metastatic effects. Fndc5/irisin exerts its biological effects through several intracellular signaling pathways. The major signaling pathway is thought to be MAPK signaling pathways which are involved in neural differentiation, browning of white adipocytes, as well as osteoblast proliferation and differentiation. Other essential functions of Fndc5/irisin are mediated through additional pathways including AMPK pathway, PI3K/AKT, and STAT3/Snail. Thorough understanding of the mechanisms of irisin actions are essential in order to develop Fndc5/irisin for therapeutic purposes. In the present review, we focus on the current knowledge of the signaling pathways that elicit irisin actions.
The experience of high-flow nasal cannula in hospitalized patients with 2019 novel coronavirus-infected pneumonia in two hospitals of Chongqing, China
Authors: Wang Ke , Zhao Wei , Li Ji , Shu Weiwei , Duan Jun
Published: March 2020

Background

The outbreak of a novel coronavirus (2019-nCoV)-infected pneumonia (NCIP) is currently ongoing in China. Most of the critically ill patients received high-flow nasal cannula (HFNC) oxygen therapy. However, the experience of HFNC in this population is lacking.

Methods

We retrospectively screened 318 confirmed patients with NCIP in two hospitals of Chongqing, China, from January 1st to March 4th, 2020. Among them, 27 (8.4%) patients experienced severe acute respiratory failure including 17 patients (63%) treated with HFNC as first-line therapy, 9 patients (33%) treated with noninvasive ventilation (NIV) and one patient (4%) treated with invasive ventilation. HFNC failure was defined by the need of NIV or intubation as rescue therapy.

Results

Of the 17 HFNC patients, 7 (41%) experienced HFNC failure. The HFNC failure rate was 0% (0/6) in patients with PaO2/FiO2 > 200 mm Hg vs. 63% (7/11) in those with PaO2/FiO2 ≤ 200 mm Hg (p = 0.04). Compared with baseline data, the respiratory rate significantly decreased after 1–2 h of HFNC in successful group [median 26 (IQR: 25–29) vs. 23 (22–25), p = 0.03]. However, it did not in the unsuccessful group. After initiation of NIV as rescue therapy among the 7 patients with HFNC failure, PaO2/FiO2 significantly improved after 1–2 h of NIV [median 172 (150–208) mmHg vs. 114 (IQR: 79–130) under HFNC, p = 0.04]. However, two out of seven (29%) patients with NIV as rescue therapy ultimately received intubation. Among the 27 patients with severe acute respiratory failure, four patients were eventually intubated (15%).

Conclusions

Our study indicated that HFNC was the most common ventilation support for patients with NCIP. Patients with lower PaO2/FiO2 were more likely to experience HFNC failure.
Movement-assisted localization from acoustic telemetry data
Authors: Hostetter Nathan J. , Royle J. Andrew
Published: March 2020

Background

Acoustic telemetry technologies are being increasingly deployed to study a variety of aquatic taxa including fishes, reptiles, and marine mammals. Large cooperative telemetry networks produce vast quantities of data useful in the study of movement, resource selection and species distribution. Efficient use of acoustic telemetry data requires estimation of acoustic source locations from detections at receivers (i.e., “localization”). Multiple processes provide information for localization estimation including detection/non-detection data at receivers, information on signal rate, and an underlying movement model describing how individuals move and utilize space. Frequently, however, localization methods only integrate a subset of these processes and do not utilize the full spatial encounter history information available from receiver arrays.

Methods

In this paper we draw analogies between the challenges of acoustic telemetry localization and newly developed methods of spatial capture-recapture (SCR). We develop a framework for localization that integrates explicit sub-models for movement, signal (or cue) rate, and detection probability, based on acoustic telemetry spatial encounter history data. This method, which we call movement-assisted localization, makes efficient use of the full encounter history data available from acoustic receiver arrays, provides localizations with fewer than three detections, and even allows for predictions to be made of the position of an individual when it wasnotdetected at all. We demonstrate these concepts by developing generalizable Bayesian formulations of the SCR movement-assisted localization model to address study-specific challenges common in acoustic telemetry studies.

Results

Simulation studies show that movement-assisted localization models improve point-wise RMSE of localization estimates by >50%and greatly increased the precision of estimated trajectories compared to localization using only the detection history of a given signal. Additionally, integrating a signal rate sub-model reduced biases in the estimation of movement, signal rate, and detection parameters observed in independent localization models.

Conclusions

Movement-assisted localization provides a flexible framework to maximize the use of acoustic telemetry data. Conceptualizing localization within an SCR framework allows extensions to a variety of data collection protocols, improves the efficiency of studies interested in movement, resource selection, and space-use, and provides a unifying framework for modeling acoustic data.
A full-polarization GNSS-R Delay-Doppler-Map (DDM) simulator for bare soil freeze/thaw process detection
Authors: Wu Xuerui , Jin Shuanggen , Ouyang Xinqiu
Published: March 2020

The soil freeze/thaw processes have a significant impact on the surface energy and moisture balance, which play a key role in ecosystem diversity and productivity. The air-/space-borne Global Navigation Satellite System (GNSS)-Reflectometry (GNSS-R) is a bistatic radar with receiving power as the Delay Doppler Map (DDM), which may monitor soil freeze/thaw processes. However, the scattering mechanism of monitoring soil freeze/thaw processes by GNSS-R DDM is not clear. In this paper, it is the first time to simulate full-polarization GNSS-R Delay-Doppler-Map (DDM) for bare soil freeze/thaw process, not only the linear polarization but also the circular polarizations. As the bare soil freeze/thaw process occurs, the corresponding DDM variations are able to present by this simulator. Other geophysical parameters, such as soil moisture and surface roughness, are also two important parameters affecting the final GNSS-R receiver power and their effects on DDM are also presented by the simulator. This simulator can be a potentially efficient tool for data analysis and interoperation of GNSS-R received power as well as the in situ experimental design.
Post-hepatectomy tolvaptan-induced hypernatremia in a hepatocellular carcinoma patient with cirrhosis: a case report
Authors: Iida Hiroya , Maehira Hiromitsu , Mori Haruki , Maekawa Tsuyoshi , Tani Masaji
Published: March 2020

Background

Tolvaptan is used in Japan to reduce fluid retention caused by cirrhosis. However, hypernatremia is one of the most important side effects. This report is the first case report of a patient who developed hypernatremia after tolvaptan administration in the early stages following hepatectomy.

Case presentation

A female patient in her 60s, who was admitted to the psychiatric department of a different hospital for bipolar disorder, developed hepatocellular carcinoma with cirrhosis. She was transferred to our hospital, and hepatectomy was performed in October 2019, after which pleural effusion and severe edema due to fluid retention were evident. Thus, the patient was started on tolvaptan (7.5 mg/day) from postoperative day (POD) 1. The patient began to experience disturbance of consciousness after POD 4. On the fifth day, the serum sodium (Na) level increased to 174 mEq/L, and hypernatremia was diagnosed. The Na level gradually improved with fluid infusion therapy, dropping to preoperative levels on the ninth day; her consciousness also gradually improved.

Conclusions

Tolvaptan administration must be performed under strictly controlled conditions, followed by careful observation during the early postoperative period, when the patient’s physical status is unstable.
Auricular neural stimulation as a new non-invasive treatment for opioid detoxification
Authors: Qureshi Imran S. , Datta-Chaudhuri Timir , Tracey Kevin J. , Pavlov Valentin A. , Chen Andrew C. H.
Published: March 2020

The recent opioid crisis is one of the rising challenges in the history of modern health care. New and effective treatment modalities with less adverse effects to alleviate and manage this modern epidemic are critically needed. The FDA has recently approved two non-invasive electrical nerve stimulators for the adjunct treatment of symptoms of acute opioid withdrawal. These devices, placed behind the ear, stimulate certain cranial nerves with auricular projections. This neural stimulation reportedly generates a prompt effect in terms of alleviation of withdrawal symptoms resulting from acute discontinuation of opioid use. Current experimental evidence indicates that this type of non-invasive neural stimulation has excellent potential to supplement medication assisted treatment in opioid detoxification with lower side effects and increased adherence to treatment. Here, we review current findings supporting the use of non-invasive neural stimulation in detoxification from opioid use. We briefly outline the neurophysiology underlying this approach of auricular electrical neural stimulation and its role in enhancing medication assisted treatment in treating symptoms of opioid withdrawal. Considering the growing deleterious impact of addictive disorders on our society, further studies on this emerging treatment modality are warranted.
Changes in the sugars, amino acids and organic acids of postharvest spermine-treated immature vegetable soybean (Glycine max L. Merr.) as determined by 1H NMR spectroscopy
Authors: Song Jiangfeng , Wu Gang , Li Tao , Liu Chunquan , Li Dajing
Published: March 2020

1H NMR spectroscopy was adopted to determine compositional changes (mainly sugars, organic acids and amino acids) involved in cold-stored immature soybean grains after exogenous spermine treatment. Significant changes of sugars, including sucrose, galactose, myo-inositol, glucose and fructose were detected in soybean after spermine treatment. As for the organic acids related to tricarboxylic acid cycle, the levels of malic and fumaric acids decreased but the level of citric acid increased. However, no significant changes were observed for amino acids in spermine-treated soybeans. By using metabolic profile analysis, a difference was observed between the aging of soybean grains as such and those treated with spermine. This study provides an insight into the accumulation of metabolites in postharvest immature soybeans after exogenous spermine-treatment.

Graphical abstract
Personality disorders in later life: epidemiology, presentation and management
Authors: Bangash Ayesha
Published: March 2020

Despite the enormous amount of literature on medical care of older people, personality disorders in late life have been given little attention. Clinicians tend not to assign this diagnosis to older adults in view of limited research into, and therefore limited awareness of, this topic. This article aims to promote better understanding of this subject in view of the growing population of older people and hence an expected increase in the number of personality disorder cases.
The Evolution of Antibody-Drug Conjugates: A Positive Inflexion Point
Authors: Tolcher Anthony W.
Published: March 2020

In 2019, an important inflection point occurred when the U.S. Food and Drug Administration approved three new antibody-drug conjugates (ADCs) for the treatment of malignancies, including urothelial cancer (enfortumab vedotin-ejfv), diffuse large B-cell lymphoma (polatuzumab vedotin-piiq), and HER2 breast cancer (fam-trastuzumab deruxtecan-nxki), and expanded the indication for ado-trastuzumab emtansine to early breast cancer. This near doubling in the number of approved ADCs within 1 year validates the ADC platform and represents a successful evolution over the past 30 years. ADCs were born in an era when systemic therapy for cancer was largely cytotoxic chemotherapy. Many of the investigational cytotoxic agents were determined to be too toxic for oral and intravenous use. The agents were especially potent, with inhibitory concentrations that inhibited 50% of cells in the nanomolar and picomolar range but had poor therapeutic indexes when administered systemically. Now, over the last 30 years, we have seen an evolution of the many aspects of this complex platform with better antigen target selection, more sophisticated chemistry for the linkers, a growing diversity of payloads from cytotoxic chemotherapy to targeted therapies and immunostimulants, and, with the recent series of regulatory approvals, a buoyed sense of optimism for the technology. Nonetheless, we have not fully realized the full potential of this platform. In this review, the many components of ADCs will be discussed, the difficulties encountered will be highlighted, the innovative strategies that are being used to improve them will be assessed, and the direction that the field is going will be considered.
A Call to Action: Ethics Committee Roundtable Recommendations for Addressing Burnout and Moral Distress in Oncology
Authors: Hlubocky Fay J. , Taylor Lynne P. , Marron Jonathan M. , Spence Rebecca A. , McGinnis Molly M. , Brown Richard F. , McFarland Daniel C. , Tetzlaff Eric D. , Gallagher Colleen M. , Rosenberg Abby R. , Popp Beth , Dragnev Konstantin , Bosserman Linda D. , Dudzinski Denise M. , Smith Sonali , Chatwal Monica , Patel Manali I. , Markham Merry J. , Levit Kathryn , Bruera Eduardo , Epstein Ronald M. , Brown Marie , Back Anthony L. , Shanafelt Tait D. , Kamal Arif H.
Published: March 2020

Oncologist well-being is critical to initiating and maintaining the physician-patient relationship, yet many oncologists suffer from symptoms of burnout. Burnout has been linked to poor physical and mental health, as well as increased medical errors, patient dissatisfaction, and workforce attrition. In this Call to Action article, we discuss causes of and interventions for burnout and moral distress in oncology, highlight existing interventions, and provide recommendations for addressing burnout and improving well-being at the individual and organizational levels to deliver ethical, quality cancer care.
Stroke in Women
Authors: Christensen Hanne , Bushnell Cheryl
Published: March 2020

PURPOSE OF REVIEW

This article reviews sex differences in stroke risk and presentation, with a particular emphasis on the unique risk factors women experience throughout the lifespan.

RECENT FINDINGS

Although prior studies suggested women have worse outcomes after stroke, it is now clear that age, prestroke functional status, and comorbidities explain many of the differences between men and women in stroke severity, functional outcomes, and mortality. Several meta-analyses and large cohort studies have evaluated the risk factors for women related to reproductive factors and found that fewer years between menarche and menopause, pregnancy complications (preeclampsia/eclampsia, preterm delivery, and stillbirth), oophorectomy, hormone replacement therapy use, and younger age at menopause all increase the risk of stroke. Although the nonreproductive risks of stroke overlap between men and women, those with greater impact on women include age, hypertension, atrial fibrillation, socioeconomic status, and depression.

Significant sex differences are observed in risk factors of stroke and stroke outcome. Including this information in the clinical assessment of the individual patient may support development of more effective prevention plans.
Surgical Approaches to Stroke Risk Reduction
Authors: Waters Michael F.
Published: March 2020

PURPOSE OF REVIEW

Surgical vascular intervention is an important tool in reducing the risk of stroke. This article examines the evidence for using the available options.

RECENT FINDINGS

Carotid endarterectomy is an effective treatment option for reducing the risk of stroke in appropriately selected patients. Patients should be stratified for future stroke risk based on both the degree of stenosis and the presence of symptoms referable to the culprit lesion. Carotid stenting is also useful in reducing stroke risk, again in carefully selected patients. Because of the publication of significant data regarding both carotid endarterectomy and carotid artery stenting in the last several years, selection can be far more personalized and refined for individual patients based on demographics, sex, patient preference, and medical comorbidities. Routine extracranial-intracranial bypass surgery remains unproven as a therapeutic option for large vessel occlusion in reducing the incidence of ischemic stroke although some carefully screened patient populations remaining at high risk may benefit; procedural risks and pathology related to alterations in blood flow dynamics are challenges to overcome. Indirect revascularization remains an appropriate solution for carefully selected patients with cerebral large vessel steno-occlusive disease, and multiple variations of surgical technique are patient specific. Indirect revascularization may benefit from clinical trials with larger patient populations for validation in specific pathologies and offers the advantages of lower surgical complication rates and reduced risk of pathologic responses to altered cerebral flow dynamics.

Surgical solutions to reduce stroke risk provide important alternatives in appropriately selected patients and should be considered in addition to medical management and lifestyle modification for optimizing patient outcomes.
Medical Management for Secondary Stroke Prevention
Authors: Kim Anthony S.
Published: March 2020

PURPOSE OF REVIEW

This article reviews the evidence base and recommendations for medical management for secondary stroke prevention.

RECENT FINDINGS

Recent developments for secondary stroke prevention include evidence to support the use of short-term dual antiplatelet therapy after minor stroke and transient ischemic attack, direct oral anticoagulants for nonvalvular atrial fibrillation, reversal agents for direct oral anticoagulant–associated hemorrhage, and aspirin rather than presumptive anticoagulation with a direct oral anticoagulant for embolic stroke of undetermined source.

Most strokes are preventable. The mainstays of medical management for secondary stroke prevention include antihypertensive therapy; antithrombotic therapy, with antiplatelet agents for most stroke subtypes or anticoagulants such as warfarin or a direct oral anticoagulant for cardioembolic stroke specifically; cholesterol-lowering therapy, principally with statins, but with potential roles for ezetimibe or proprotein convertase subtilisin/kexin type 9 inhibitors in selected patients; and glycemic control to prevent microvascular complications from diabetes mellitus or pioglitazone in selected patients with insulin resistance but not diabetes mellitus.
Innovations in Prehospital Stroke Management Utilizing Mobile Stroke Units
Authors: Alexandrov Anne W. , Alexandrov Andrei V.
Published: March 2020

Using a representative case, this article discusses prehospital innovations for patients with acute large vessel occlusion ischemic stroke, including mobile stroke unit care supported by advanced field imaging.
Endovascular Treatment of Acute Ischemic Stroke
Authors: Silva Gisele S. , Nogueira Raul G.
Published: March 2020

PURPOSE OF REVIEW

This article reviews the actual indications for mechanical thrombectomy in patients with acute ischemic stroke and how the opportunities for endovascular therapy can be expanded by using the concept of clinical-imaging or perfusion-imaging mismatch (as a surrogate for salvageable tissue) rather than time of ischemia.

RECENT FINDINGS

Six randomized controlled trials undoubtedly confirmed the benefits of using endovascular thrombectomy on the clinical outcome of patients with stroke with large vessel occlusion within 6 hours from symptom onset compared with those receiving only standard medical care. In a meta-analysis of individual patient data, the number needed to treat with endovascular thrombectomy to reduce disability by at least one level on the modified Rankin Scale for one patient was 2.6. Recently, the concept of “tissue window” versus time window has proved useful for selecting patients for mechanical thrombectomy up to 24 hours from symptom onset. The DAWN (DWI or CTP Assessment With Clinical Mismatch in the Triage of Wake-Up and Late Presenting Strokes Undergoing Neurointervention) trial included patients at a median of 12.5 hours from onset and showed the largest effect in functional outcome ever described in any acute stroke treatment trial (35.5% increase in functional independence). In DEFUSE 3 (Diffusion and Perfusion Imaging Evaluation for Understanding Stroke Evolution 3), patients treated with mechanical thrombectomy at a median of 11 hours after onset had a 28% increase in functional independence and an additional 20% absolute reduction in death or severe disability.

For patients with acute ischemic stroke and a large vessel occlusion in the proximal anterior circulation who can be treated within 6 hours of stroke symptom onset, mechanical thrombectomy with a second-generation stent retriever or a catheter aspiration device should be indicated regardless of whether the patient received treatment with intravenous (IV) recombinant tissue plasminogen activator (rtPA) in patients with limited signs of early ischemic changes on neuroimaging. Two clinical trials completely disrupted the time window concept in acute ischemic stroke, showing excellent clinical outcomes in patients treated up to 24 hours from symptom onset. Time of ischemia is, on average, a good biomarker for tissue viability; however, the window of opportunity for treatment varies across different individuals because of a range of compensatory mechanisms. Adjusting time to the adequacy of collateral flow leads to the concept of tissue window, a paradigm shift in stroke reperfusion therapy.
Iatrogenic Aortic Intramural Hematoma: Guidance to Intraoperative Decision Making: A Case Report
Authors: Ram Harish , Weaver Andrew R. , Dorfling Johannes
Published: March 2020

Aortic intramural hematoma (IMH) is a collection of blood within the aortic wall without an identifiable intimal tear. It belongs to the spectrum of acute aortic syndrome (AAS) which also includes aortic dissection (AD), a well-defined entity. Principles of management guided by Stanford classification is similar in both entities. But with recent advances in imaging, certain features of IMH have been identified that affect the natural course of IMH. We report a unique case of iatrogenic IMH complicating a routine coronary artery bypass graft surgery (CABG) and how imaging guided intraoperative decision making toward conservative management.
Did Unconventional Interventions Unfreeze the Credit Market?
Authors: Tong Hui , Wei Shang-Jin
Published: March 2020

This paper investigates whether and how unconventional interventions in 2008–2010 unfroze the credit market. We construct a dataset of 198 interventions for 16 countries during 2008–2010 and examine heterogeneous responses in stock prices to the interventions across 7,873 nonfinancial firms in those countries. Stock prices increase when the interventions are announced, particularly for firms with greater intrinsic need for external capital. This pattern is corroborated by subsequent expansions in firm investment, R&D expenditure, and employment. Among various forms of interventions, recapitalization of banks appears particularly effective in channeling the intervention effects from financial to nonfinancial sectors. (JEL E44, E58, G01, G14, G21, G31, G32)
Dynamic Debt Deleveraging and Optimal Monetary Policy
Authors: Benigno Pierpaolo , Eggertsson Gauti B. , Romei Federica
Published: March 2020

This paper proposes a postcrisis New Keynesian model that incorporates agent heterogeneity in borrowing and lending with a minimum set of assumptions. Unlike the standard framework, this model makes the natural rate of interest endogenous and dependent on macroeconomic policy. The main application is to study optimal monetary policy at the zero lower bound (ZLB). Such policy succeeds in raising the natural rate of interest by creating an environment that speeds up deleveraging and thus endogenously shortens the crisis and the duration of binding ZLB. Inflation should be front-loaded and should overshoot its long-term target during the ZLB episode. (JEL E12, E31, E32, E43, E52)
What is known about the protective factors that promote LGBTI+ youth wellbeing? A scoping review protocol
Authors: Ceatha Nerilee , Bustillo Marta , Tully Louise , James Oscar , Crowley Des
Published: March 2020

Background: There is much concern at the substantial vulnerabilities experienced by lesbian, gay, bisexual, transgender and intersex (LGBTI+) youth as a consequence of discrimination, stigmatisation and marginalisation. Recent research highlights the importance of understanding factors that can promote wellbeing for this population. This paper presents a protocol for a scoping review which aims to systematically map and synthesise the extent and nature of the peer-reviewed, published academic literature on the protective factors that promote wellbeing for sexual and gender minority young people.

Methods: In accordance with the methodological framework for scoping reviews, the following six stages will be undertaken: (1) identifying the research question, (2) identifying relevant studies, (3) study selection, (4) charting the data, (5) collating, summarising and reporting results and (6) consultation. The PRISMA Extension for Scoping Reviews (PRISMA-ScR): Checklist and Explanation will be used throughout the review process. Key inclusion criteria will use the Population, Concept, Context approach, with two reviewers independently conducting the screening and extraction stages across five databases. Identified protective factors will be collated, summarised and categorised iteratively by one reviewer in consultation with the review team. Stakeholder consultation is a key strength of the scoping review process and will be complemented by the public patient involvement of LGBTI+ young people with expertise by experience.

Conclusions: The scoping review has the potential to inform policy, practice and future research through enhanced understandings of the complex interplay of factors that promote wellbeing for sexual and gender minority youth. This first stage of the research process will inform the development of a larger research project. The findings will be disseminated through a peer reviewed publication, a conference presentation and by sharing the findings with key stakeholders, including LGBTI+ young people.
Quasi-periodic pulsations in solar and stellar flares. Review
Authors: Kupriyanova Elena , Kolotkov Dmitrii , Nakariakov Valery , Kaufman Anastasiia
Published: March 2020

This paper provides an overview of the state-of-the-art studies of oscillatory processes in solar and stellar flares, based on modern observational data from ground-based and space-borne instruments with high temporal, spatial, and spectral resolution in different electro-magnetic spectrum ranges. We examine the mechanisms that generate flare emission and its quasi-periodic modulation. We discuss similarities and differences between solar and stellar flares, and address associated problems of superflares on the Sun and space weather problems. Quasi-periodic pulsations (QPPs) of flare radiation are shown to be an effective tool for diagnosing both the flare processes themselves and the parameters of flare plasma and accelerated particles. We consider types of QPPs, their statistical properties, and methods of analysis, taking into account the non-stationarity of the QPPs’ parameters. We review the proposed mechanisms of QPPs and address open questions.
Spatial structure of azimuthally small-scale MHD waves in one-dimensionally inhomogeneous finite pressure plasma with curved field lines
Authors: Petrashchuk Aleksandr , Klimushkin Dmitri
Published: March 2020

We have studied propagation of hydromagnetic (MHD) waves in one-dimensionally inhomogeneous finite pressure plasma with curved field lines. Magnetic surfaces are considered to be concentric cylinders, where the cylinder’s radius models the radial coordinate in Earth’s magnetosphere. The waves are supposed to be azimuthally small-scale. In this approximation there are only two MHD modes — Alfvén and slow magnetosonic (SMS). We have derived an ordinary differential equation for the spatial structure of the wave field in this model. We have examined the character of the singularity on the surface of Alfvén and SMS resonances and the influence of field line curvature on them. We have determined wave transparent regions. The SMS transparent region was found to essentially broaden as compared to the straight field line case. The very existence of the Alfvén transparent region is caused by the field line curvature and finite plasma pressure; otherwise, the wave structure is represented by a localized resonance.
Muon intensity variations and atmospheric temperature
Authors: Yanchukovsky Valery
Published: March 2020

Muons in the atmosphere are formed during the decay of pions resulting from nuclear interactions of cosmic rays with nuclei of air atoms. The resulting muons are also unstable particles with a short lifetime. Therefore, not all of them reach the level of observation in the atmosphere. When the atmospheric temperature changes, the distance to the observation level changes too, thus leading to variations in the intensity of muons of temperature origin. These variations, caused by atmospheric temperature variations, are superimposed on continuous observations of muon telescopes. Their exclusion is, therefore, extremely necessary, especially in the data from modern muon telescopes whose statistical accuracy is very high. The contribution of various atmospheric layers to the total temperature effect is not the same for muons. This contribution is characterized by the distribution of the density of temperature coefficients for muons in the atmosphere. Using this distribution and the continuous intensity observations from the muon telescope in Novosibirsk, the inverse problem has been solved, from the solution of which the atmospheric temperature variations over a long period from 2004 to 2011 have been found. The results obtained are compared with aerological sounding data.
The impact of the moon phase on the balance of the autonomous nervous system and the functional health of men of different age groups
Authors: Yermishev O. V.
Published: March 2020

Introduction. The autonomic nervous system is the main regulatory mechanism of a living organism that provides homeostasis. Objective: to investigate the effect of the Moon phases on the autonomic balance of the human body, the ratio of sympathetic nervous system activity to the parasympathetic nervous system and the functional health of the population. Materials and methods. 1592 males of different age were examined with the help of functional vegetative diagnostics according to the method of V. Makats. The bioelectric activity of 12 symmetric pairs of functionally active zones of the skin (24 FAZ), 12 on the hands and 12 on the feet, which reflect the functional activity of the sympathetic and parasympathetic nervous systems were studied. Results. In the male group aged 3-6 years old, the chaotic pattern of functional dependencies is related to the physiological and functional immaturity of the adaptation processes and the speed of their formation and stabilization in the body of children. In the male group of 12-15 years old in different phases of the Moon the changes in activity indicators of functional systems with much smaller amplitude are observed, though the nature and direction of changes in activity remain similar, which indicates the stabilization of adaptation mechanisms in the body. In the male group aged 21-50 years old maximum amplitude fluctuations in the functional activity of the systems and vegetative homeostasis are observed in the new Moon and the full one, which indicates a decrease in adaptation processes associated with age-related decrease in physiological and biochemical processes in the body and the appearance of the organism in the body. Conclusions. It has been established that the change of the Moon phases leads to significant changes in the functional activity and homeostasis of the body of men of different age groups. On-phase Moon activity indicators of functional systems duplicating the norm line have the same orientation, differing in amplitude, forming age-specific features of the tone of the autonomic nervous system.
Role of food and nutrition and prevention in pathogenesis of the arterial occlusive disease
Authors: Reba Patricia
Published: March 2020

Admission          Atherosclerosis is a chronic inflammatory disease of complex etiopathogenesis. Improper diet, genetic predisposition, lack of physical activity, and smoking are just a few of the major factors contributing to the development of atherosclerotic plaque. Diet in atherosclerosis, treatment is based. Antiatherosclerotic diet is one of many components, which should provide not only the treatment of such a state, but primarily prevention. Accordingly, balanced nutrition regimen can reduce cholesterol synthesis in the liver, which contributes to the development of atherosclerosis. Limiting the intake of trans fatty acids and saturated fatty acids allows for inhibiting the development of atherosclerotic plaque.AimThe aim of the study is to analyze the role of food and nutrition in the prevention and pathogenesis of atherosclerosis of the lower extremities.Material and methodsA review of available literature.Results          Adequate intake of potassium in the diet contributes significantly to reducing the risk of atherosclerosis and hypertension. Potassium determines many important functions in the body.Due to the fact that the monounsaturated fatty acids reduce LDL cholesterol levels, the proportion should be in the diet increased to 15% and for the secondary prevention of up to 20%. In the prevention of atherosclerosis is very important to maintain an appropriate ratio of omega-6 to omega-3 ratio is absolutely should be no more than 4. It is extremely important in the diet because distorted value for the benefit of omega-6 favors the formation of atherosclerotic lesions.respective supply of carbohydrates also has a huge impact on the development of atherosclerotic lesions. The recommended amount of antiatherosclerotic dietary up to 60% provided that the people do not apply to such ailments as hypertension, overweight or obesity, elevated fasting blood sugar levels, decreased HDL cholesterol and elevated triglycerides.ConclusionsGeneral nutritional recommendations play the role of a signpost, which you should use expecting to improve health. It should be noted, however, that is not all. Nutritional prevention is significant, but equally important is lifestyle modification. Atherosclerotic diet is an important part of the treatment of the disease and prevent further growth of atherosclerotic plaque. Atherosclerosis requires the use of low-fat diet that is necessary to beat high blood cholesterol levels.
Targeted therapy in age-related macular degeneration (AMD)
Authors: Szumna Klaudia Daria , Piędel Faustyna , Rocka Agata Agnieszka , Madras Dominika Katarzyna , Jasielski Patryk Piotr
Published: March 2020

Introduction and purpose: Age-related macular degeneration (AMD) is a major cause of blindness in highly developed countries, with blindness frequency of 8.7%. This article is a review of the latest therapeutic options for AMD.A brief description of the state of knowledge: AMD is a multifactorial disease which etiology is not completely understood. Its development is affected by disorders at the cellular level, environmental and genetic factors. Intraocular injections of anti-VEGF agents are currently considered as the basis of AMD neovascular treatment. In the search for better and better therapeutic agents, the effects of administration of bevacizumab and ranizumab were tested. Many clinical studies confirm long-term and effective improvement in patients' vision after using the above-mentioned drugs, indicating that the initial response to treatment and the persistence of the therapeutic effect is individually variable and may be associated with genotypic difference. Another promising alternative to AMD treatment is the use of specific viral vectors that transfer substances slowing down the disease into the vitreous. Another method of gene therapy is the use of HIF transcription factors (hypoxia-induced factors), for now, the research is performed on animal models. Patients with dry AMD also have a chance for successful treatment. Examined gene therapy in dry form of AMD, including retinal surgery combined with viral vector injection, is in I/II phase study in Great Britain.  Conclusions: Looking at the number of blindness cases in highly developed countries caused by AMD, every effort should be made to introduce effective treatment that at least inhibits disease progression. Undoubtedly, more research is needed to confirm the efficacy and long-term safety of AMD.
Targeted therapy with Poly(ADP-ribose) polymerase (PARP) inhibitors for the treatment of solid tumours
Authors: Piędel Faustyna , Rocka Agata Agnieszka , Szumna Klaudia Daria , Madras Dominika Katarzyna , Jasielski Patryk Piotr
Published: March 2020

Introduction: According to the National Cancer Register in Poland, the number of cancers including breast cancers has more than doubled in the past three decades. Poly(ADP-ribose) polymerase (PARP) inhibitors lead to the death of cells with a BRCA1/2 mutation. The use of PARP inhibitors has increased significantly over the last 5 years.Objective: This article summarizes the current knowledge about the safety and clinical  efficacy of PARP inhibitors in the treatment of solid tumors.Abbreviated description of the state of knowledge: PARP inhibitors have been used in the standard treatment of ovarian cancer. Three of them: Olaparyb, Rucaparyb and Niraparyb have indications for maintenance treatment in recurrent platinum-sensitive ovarian cancer. Olaparib and Weliparib are used to treat breast cancer patients. Research shows that the use of Olaparib in breast cancer patients has reduced tumours size as much as around 60% of women with BRCA mutation. The combination of veloparin with carbolatin and paclitaxel was associated with a longer mean survival period than chemotherapy alone in treatment of non-small cell lung cancer(NSCLC).In addition, there are studies showing the benefits of PARP inhibitor therapy in prostate cancer. Olaparyb in combination with abiraterone shows greater clinical efficacy in patients with castration-resistant prostate cancer compared alone abiraterone.Conclusions: FDA approval of new PARP inhibitors is a promising method for more effective treatment of the most common cancers in the world. In the future further research may lead to a better definition of the patient group benefiting most from PARP inhibitor therapy.
The Guidance and Sports Development Achievements in Sragen Regency Based Local Excellence
Authors: Sulistiyo Sulistiyo , Kristiyanto Agus , Purnama Sapta Kunta
Published: March 2020

This research attempts to find out the government Sragen Regency on implementing Law No. 3 in 2005 chapter 34 about the district/city government is obliged to manage at least one superior sports national and/or international standard. This research using the methodology descriptive qualitative. Research data sources such as 2 employees DISPORA, 2 employees KONI Sragen Regency, 2 athletes and 2 coach. Data collection techniques using interviews. Data analysis techniques use descriptive analysis.         Based on the results of research can be concluded as follows: (1) the district government Sragen not implement Law No. 3 in 2005 Chapter 34, (2) KONI not focus on 1 superior sports, KONI focusing on the main tasks KONI to improve performance, (3) Executive power in increasing the achievement is coach, (4) Funding from KONI 85% directed to the development of sport and DISPORA direct funding for sports competition, (5) Infrastructures in condition enabling, (6) Coaching done through P3B program (Nursery Sustainable Development Program) and Prosukma (Gold Sukowati Program).