bluuebunny/crossref_metadata_2025 huggingface dataset:
Therapeutic applications of CRISPR/Cas9 in breast cancer and delivery potential of gold nanomaterials
Authors: Padayachee Jananee , Singh Moganavelli
Published: December 2020

Globally, approximately 1 in 4 cancers in women are diagnosed as breast cancer (BC). Despite significant advances in the diagnosis and therapy BCs, many patients develop metastases or relapses. Hence, novel therapeutic strategies are required, that can selectively and efficiently kill malignant cells. Direct targeting of the genetic and epigenetic aberrations that occur in BC development is a promising strategy to overcome the limitations of current therapies, which target the tumour phenotype. The clustered regularly interspaced short palindromic repeats (CRISPR)/Cas system, composed of only an easily modifiable single guide RNA (sgRNA) sequence bound to a Cas9 nuclease, has revolutionised genome editing due to its simplicity and efficiency compared to earlier systems. CRISPR/Cas9 and its associated catalytically inactivated dCas9 variants facilitate the knockout of overexpressed genes, correction of mutations in inactivated genes, and reprogramming of the epigenetic landscape to impair BC growth. To achieve efficient genome editing in vivo, a vector is required to deliver the components to target cells. Gold nanomaterials, including gold nanoparticles and nanoclusters, display many advantageous characteristics that have facilitated their widespread use in theranostics, as delivery vehicles, and imaging and photothermal agents. This review highlights the therapeutic applications of CRISPR/Cas9 in treating BCs, and briefly describes gold nanomaterials and their potential in CRISPR/Cas9 delivery.
An Exploration of Five Stages in Faculty Retirement Decision Making
Authors: Anderson Beverlee B. , Jeffries Jennifer , McDaniel Janet
Published: December 2020

Humans make thousands of decisions each day. Most of the decisions we make are trivial or relatively unimportant in possible consequences. However, there are a few decisions we make in life that are lifechanging; one of those is the decision to retire from the professoriate. Voluntarily deciding to leave a profession where one has spent a substantial portion of one’s working life is one of life’s major decisions. This qualitative research looks at the various influences, actions, and feelings through the process of deciding to retire. Using a five-stage cognitive decision-process model as a framework, this paper reports on the reflections of 20 recent retirees over the five stages of the decision process from when first seriously considering the decision to postretirement activities and feelings. The results show that while all faculty progressed through the five stages, the timeframe, influences, feelings, and actions were unique to each individual.
LPCAT2 Methylation, a Novel Biomarker for the Severity of Cedar Pollen Allergic Rhinitis in Japan
Authors: Watanabe Hiroyuki , Miyake Kunio , Matsuoka Tomokazu , Kojima Reiji , Sakurai Daiju , Masuyama Keisuke , Yamagata Zentaro
Published: December 2020

Background

Recently, the role of the epigenome in allergies has been receiving increasing attention. Although several genes that are methylated in relation to serum immunoglobulin E (IgE) concentration have been reported by epigenome-wide association studies, little is known about the DNA methylation sites associated with the symptoms and severity of cedar pollinosis (CP).

Objective

Our aim was to analyze the association between DNA methylation and the symptoms and severity of CP in peripheral blood mononuclear cells (PBMCs) and nasal mucosa scraping cells (NMSCs).

Methods

We recruited 70 participants during the cedar pollen dispersal season. IgE levels were measured by a fluorescence enzyme immunoassay. We analyzed DNA methylation of acyl-CoA thioesterase 7 ( ACOT7), mucin 4 ( MUC4), schlafen 12 ( SLFN12), lysophosphatidylcholine acyltransferase 2 ( LPCAT2), and interleukin-4 ( IL4) in PBMCs and NMSCs using bisulfite next-generation sequencing; the correlation of DNA methylation with non-specific IgE and cedar pollen-specific IgE levels in peripheral blood samples was also investigated. Symptom severity and DNA methylation were investigated in 15 untreated CP patients.

Results

Non-specific IgE levels showed a significant negative correlation with average IL4 methylation in PBMCs (r = −0.46, P < 0.0001) but not with methylation of ACOT7, MUC4, SLFN12, and LPCAT2. Cedar pollen-specific IgE levels showed a significant negative correlation with average IL4 and MUC4 methylation in PBMCs (r = −0.31, P = 0.01 and r = −0.241, P = 0.046, respectively) but not with methylation of ACOT7, SLFN12, and LPCAT2. The methylation of some genes in NMSCs was not significantly correlated with IgE levels. The mean methylation of LPCAT2 in NMSCs showed a decreasing trend with increasing severity of CP (P = 0.027).

Conclusion

LPCAT2 methylation in NMSCs may reflect the severity of CP and could be used as a novel biomarker to identify suitable treatment options for CP.
Analyzing Response Times and Other Types of Time-to-Event Data Using Event History Analysis: A Tool for Mental Chronometry and Cognitive Psychophysiology
Authors: Panis Sven , Schmidt Filipp , Wolkersdorfer Maximilian P. , Schmidt Thomas
Published: December 2020

In this Methods article, we discuss and illustrate a unifying, principled way to analyze response time data from psychological experiments—and all other types of time-to-event data. We advocate the general application of discrete-time event history analysis (EHA) which is a well-established, intuitive longitudinal approach to statistically describe and model the shape of time-to-event distributions. After discussing the theoretical background behind the so-called hazard function of event occurrence in both continuous and discrete time units, we illustrate how to calculate and interpret the descriptive statistics provided by discrete-time EHA using two example data sets (masked priming, visual search). In case of discrimination data, the hazard analysis of response occurrence can be extended with a microlevel speed-accuracy trade-off analysis. We then discuss different approaches for obtaining inferential statistics. We consider the advantages and disadvantages of a principled use of discrete-time EHA for time-to-event data compared to (a) comparing means with analysis of variance, (b) other distributional methods available in the literature such as delta plots and continuous-time EHA methods, and (c) only fitting parametric distributions or computational models to empirical data. We conclude that statistically controlling for the passage of time during data analysis is equally important as experimental control during the design of an experiment, to understand human behavior in our experimental paradigms.
Protracted withdrawal syndrome after stopping antidepressants: a descriptive quantitative analysis of consumer narratives from a large internet forum
Authors: Hengartner Michael P. , Schulthess Lukas , Sorensen Anders , Framer Adele
Published: December 2020

Background:

Protracted withdrawal syndrome (PWS) after stopping antidepressants (frequently also referred to as post-acute withdrawal syndrome or PAWS) has been described in a few case reports. However, a detailed quantitative analysis of specific symptom manifestations in antidepressant PWS is still lacking.

Methods:

We extracted patient narratives from a large English-language internet forum SurvivingAntidepressants.org , a peer support site concerned about withdrawal from antidepressants. PWS was ascertained based on diagnostic criteria proposed by Chouinard and Chouinard, specifically ⩾6 months of continuous antidepressant use, with emergence of new and/or more intense symptoms after discontinuation that last beyond the initial 6 weeks of acute withdrawal. We assessed medication history, outcome of PWS, and the prevalence of specific symptoms.

Results:

In total, n = 69 individual reports of protracted withdrawal were selected for analysis. At time of the subjects’ most recent reports, duration of PWS ranged from 5 to 166 months, mean = 37 months, median = 26 months. Length of time on the antidepressant causing protracted withdrawal ranged from 6 to 278 months, mean = 96 months, and median = 79 months. Throughout the withdrawal experience, affective symptoms, mostly anxiety, depression, emerging suicidality and agitation, were reported by 81%. Somatic symptoms, mostly headache, fatigue, dizziness, brain zaps, visual changes, muscle aches, tremor, diarrhea, and nausea were reported by 75%. Sleep problems (44%) and cognitive impairments (32%) were mentioned less frequently. These broad symptom domains were largely uncorrelated.

Conclusion:

PWS or PAWS from antidepressants can be severe and long-lasting, and its manifestations clinically heterogeneous. Long-term antidepressant exposure may cause multiple body system impairments. Although both somatic and affective symptoms are frequent, they are mostly unrelated in terms of occurrence. Proper recognition and detection of PWS thus requires a comprehensive assessment of medication history, duration of the withdrawal syndrome, and its various somatic, affective, sleep, and cognitive symptoms.
Stable patients with schizophrenia switched to paliperidone palmitate 3-monthly formulation in a naturalistic setting: impact of patient age and disease duration on outcomes
Authors: Pungor Katalin , Bozikas Vasilis P. , Emsley Robin , Llorca Pierre-Michel , Gopal Srihari , Mathews Maju , Wooller Annette , Bergmans Paul
Published: December 2020

Background:

Paliperidone palmitate 3-monthly (PP3M) is a second-generation, long-acting injectable antipsychotic formulation indicated for the maintenance treatment of adults with schizophrenia first stabilized with paliperidone palmitate 1-monthly (PP1M). This exploratory post hoc subgroup analysis of the 52-week, phase 3b REMISSIO study analysed outcomes according to patient age and disease duration in a naturalistic clinical setting.

Methods:

Outcomes of patients with schizophrenia were analysed according to age [<35 years ( n = 123) versus ⩾35 years ( n = 182)] and disease duration [⩽3 years ( n = 72) versus >3 years ( n = 233)]. The primary efficacy outcome was the proportion of patients achieving symptomatic remission according to the Andreasen criteria. Adverse events were monitored throughout the study.

Results:

At endpoint (last observation carried forward), 60.7% (95% CI: 51.4%, 69.4%) of younger patients and 54.1% of older patients (95% CI: 46.6%, 61.6%) achieved symptomatic remission. The proportions for patients with disease duration ⩽3 years and >3 years were similar: 57.8% (45.4%, 69.4%) versus 56.5% (49.8%, 62.9%). Functional remission was reached by 45.4% (36.2%, 54.8%) of patients aged <35 years and 36% (28.9%, 43.6%) of patients aged ⩾35 years with a similar pattern when analysed by disease duration. PP3M had a favourable safety profile and was generally well tolerated in both age groups.

Conclusion:

Patients with schizophrenia, previously stabilized on PP1M, may benefit from PP3M treatment with some additional potential improvements if started early in the disease course.

Clinical trials.gov:

NCT02713282
SARS-CoV-2 (COVID-19) PCR cycle threshold: can it help in the timing of urgent cardiac surgery?
Authors: Alkhulaifi Abdulaziz , Mohammed Shady , Lone Hafeez , Wani Mohd , Shoman Bassam , Elhassan Mawahib , Althani Asmaa , Carr Cornelia S
Published: December 2020

Background

The COVID-19 pandemic has resulted in a significant reduction in urgent cardiac surgery due to concerns about safety for both patients and care givers. The timing of safe cardiac surgery is yet to be clarified in the setting of COVID-19 diagnosis.

Methods

Due to the urgency of the cardiac conditions on presentation, we have operated on four patients who exhibited the spectrum of COVID-19 disease from asymptomatic to severe COVID-19 pneumonia. With the evolving knowledge about SARS-CoV-2 and its genetic determinants as well as the cycle threshold levels obtained from real-time reverse transcription polymerase chain reaction, we have attempted to develop a strategy to deal with these patients.

Results

All four patients underwent urgent cardiac surgery following a thorough evaluation and multidisciplinary team approach with guidance based on the virus cycle threshold values obtained by reverse transcription polymerase chain reaction.

Conclusion

We have shown that, with thorough preparations, consideration of the significance of the cycle threshold obtained on reverse transcription polymerase chain reaction and meticulous timing, COVID-19 diagnosed patients may undergo open heart surgery safely.
Negotiating Leadership in Interdisciplinary Co-Productive Research: A Case Study of An International Community-Based Project Between Collaborators From South Africa and the United Kingdom
Authors: Hart Angie , Biggs Shahnaz , Scott-Bottoms Stephen , Buttery Lisa , Dennis Scott , Duncan Simon , Ebersöhn Liesel , Flegg Mirika , Kelso Clare , Khaile Neo Mosna , Mampane Motlalepule Ruth , Mampane Ngwanangwato Selogadi , Nash David J. , Ngoma Richard , Theron Linda C.
Published: December 2020

In the absence of empirical and conceptual considerations of the negotiation of leadership in teams doing community-based research, this article adds to the leadership literature by offering a critical reflection on positioning and collaborative teams in the context of one interdisciplinary, co-productive, cross-generational and international research project. The project focused on youth and community resilience to drought in South Africa. Fourteen co-researchers reflected on their experiences of leadership within the project, using a collectively developed questionnaire. Findings uniquely highlight wider ethical considerations when youth and novice researchers are included in research teams. A strong emphasis on cultural responsiveness was found; with local and culturally led leadership seen to positively influence both processes and outcomes. Reflections suggest collaboration may be approached as an “ethos” and aided by transformational leadership theories and methodologies. Findings may be especially relevant to research teams, funders, and ethical bodies.
The Experience of Poverty Reduction in Rural China
Authors: Fang Conglong , Gai Qingen , He Chaofei , Shi Qinghua
Published: December 2020

Since 1978, China has greatly reduced the rural poverty rate. This article provides an overview of the experience of China’s poverty reduction. Using panel data from 1996 to 2013 to calculate farmers’ income dynamics, we found that the pace of poverty reduction was relatively slow from 1996 to 2002 and that the rate of reversion to poverty was high. Since 2003, the pace of poverty reduction has accelerated, whereas the rate of reversion has decreased. Using econometric ordinary least squares and probit models, we explore the factors that drive poverty reduction. We found correlational evidence that the main reasons for poverty reduction in China since 1996 have been the increase in income from household farms and migrant work. In addition, rural public insurance prevented farmers from falling into poverty.
Factors Influencing Job Satisfaction in Hospitality Industry
Authors: Heimerl Peter , Haid Marco , Benedikt Lea , Scholl-Grissemann Ursula
Published: December 2020

Finding and keeping qualified workers is an evident problem in the hospitality industry in many parts of the Alpine region. Job satisfaction is, therefore, becoming increasingly important for sustainable development of the labor market and in further consequence regions and destinations. Hence, this study aims to examine factors influencing job satisfaction to gain a better understanding. A total of 345 employees were surveyed on aspects of job satisfaction using an online questionnaire. Data analyses show that a positive relationship with the supervisor, adherence to the duty roster, and personal development opportunities are the most important factors for job satisfaction. In contrast, remuneration, task portfolio, working atmosphere, and the infrastructure provided were less important drivers. The findings highlight important areas and directions for further investigation of job satisfaction. For practitioners, the study offers valuable insights into the sustainable and effective promotion of employee job satisfaction.
Political Economy of Inequality of Rural Bengal in Post-Reform Period: Development or Proletarization?
Authors: Biswas Debolina
Published: December 2020

This article examines agricultural growth and rural inequality in West Bengal during the post-reform period. Two qualitatively different phases of growth and inequality are identified: from 1993–1994 to 2004–2005, when agricultural growth in West Bengal was moderately higher compared to all of India, but the state witnessed increasing rural inequality; and from 2004–2005 to 2009–2010, when agrarian growth decelerated and rural inequality declined. To unravel the underlying changes in rural inequality, this study uses a class framework and suggests certain plausible explanations. It shows that the benefits of good agricultural growth in the first period were reaped by the middle and small farmers; moreover, it is possible that a shift in population occurred from these classes toward the absentee landlord class who are also self-employed in the nonfarm sector. During the next period, the deceleration of agrarian growth was associated with a sharp decline in the proportion of population of the farming classes and increase in the population share of the poorer classes, that is, agricultural labor and nonagricultural worker. Hence, declining inequality does not necessarily signify development, since the poorer classes evidently did not experience any real improvement; rather, a process of proletarization has begun in rural Bengal.
Land as Home in South Africa: The Living and the Dead in Ritual Conversations
Authors: Borges Antonádia
Published: December 2020

Apartheid segregated not only the living, but also the dead. Taking a wedding ritual as its departure point, the article explores the conversations between the living and the dead taking place in a redistributed farm in KwaZulu-Natal, South Africa. Conviviality between the living and the dead challenges the idea of pecuniary compensation as an adequate land reform policy insofar its beneficiary population expands to the infinite, including those now alive, the living who have already died, and those yet to be born. If these ritual conversations suggest that the past and future are experiential moments beyond what is lived today, it would appear our duty to devise alternatives to the linear, flat, and cumulative narratives that currently dominate our academic work and our political practice.
The Far Right: Formidable but Not Unbeatable
Authors: Bello Walden
Published: December 2020

The level of discontent and alienation with neoliberalism was already very high in the Global North before the coronavirus hit, owing to the inability of the established elites to reverse the decline and living standards and skyrocketing inequality in the dreary decade that followed the financial crisis. And in much of the Global South, the chronic crisis of underdevelopment under peripheral capitalism, exacerbated by neoliberal ‘reforms’ since the 1980s, had already shredded the legitimacy of key institutions of globalization. This article seeks to identify key elements in the rise of the far right in the Global North and the Global South and indicates steps that need to be taken to confront the far right.
Flipped Exam Room
Authors: Conway Katharine , Hershberger Paul J , Bricker Dean A , Castle Angela
Published: December 2020

Medical education has taken a decided turn toward the “flipped classroom,” in which in-class lectures are de-emphasized and engaged learning is promoted. The time has also come to make some changes in what is being taught in clinical medicine, specifically with respect to the patient-physician interaction. Because the daily management of chronic illness is primarily the responsibility of the patient, clinical encounters that prioritize patient engagement and activation are critical. The traditional medical encounter, characterized by data gathering to make a diagnosis followed by prescribing or recommending treatment to the patient, can work well for acute illnesses or injuries, but effective chronic disease management requires substantial patient ownership of their health. In a “flipped exam room,” interactions with patients emphasize patient responsibility for health, such that priority is given to eliciting patient goals, what the patient knows, and how they desire to proceed with management of their health concerns and conditions. Just as medical students find engaged learning approaches to be more acceptable and satisfying, patients find collaborative interaction approaches on the part of their physicians to be more satisfying, and such approaches are associated with better outcomes. More attention to training students and residents in “flipped exam room” patient interaction skills is necessary.
Determinants of Using Social Networking Sites Toward Entrepreneurial Success: Experience from a Developing Nation
Authors: Momen Md. Abdul , Shahriar Shamsul Huq Bin , Hassan Md. Kamrul , Sultana Seyama
Published: December 2020

The study presents the determinants of the usage of social networking sites (SNSs) to accelerate the business potential of young entrepreneurs in a developing nation. It’s a quantitative study that considers 168 young entrepreneurs of Bangladesh. In analyzing the data, exploratory factor analysis has been used to justify the items associated with each variable while using a structural equation modeling approach to test the driven hypothesis. The study reveals that using social media as a promotional tool helps entrepreneurs to hasten their venture. In addition, changing purchasing behavior in this digital era and convenience and speed of Internet access also influence them to use SNSs intensively for growing their business enterprise. The findings of the study will help the key stakeholders to initiate key steps in order to create a more favorable business environment particularly for young entrepreneurs in this digital age of communication.
Banking Outreach: A Geographic and Demographic Analysis for Countries of the Gulf Cooperation Council
Authors: Bhandari Vibha , Mohite Vikram
Published: December 2020

Financial system development and growth share a two-way relationship. A developed financial system enterprises real growth and a growing economy’s demand leads to the development of the financial sector. In order to realize the goals of development, it is important that the financial system should not only be developed but also be inclusive. Banking system/institutions of countries have played a vital role in promoting and establishing financial systems to meet the requirements of the majority of people. Improved access to banks results in financial inclusion and sustainable development. Globally, the country governments have made several policy decisions and adopted regulations to ensure that banks reach to majority of the people. This article aims to analyze the banking outreach for the countries of GCC for a period of seven years from 2010 to 2017. This analysis will be based on geographic and demographic indicators of the outreach of banks’ physical outlets in the form of bank branches and its ATMs. This analysis will help to identify the countries of GCC with easier geographic and demographic access.
Exploring the potential of urban (re)form: Modifying gated communities to shorten school travel distance in Nanjing, China
Authors: Han Lingyun , Xu Zhen , Sabel Clive
Published: December 2020

The distance between home and school considerably influences the probability of children’s walking or biking to school (termed Active School Travel) which is a significant opportunity to promote their daily physical activity. This study investigated the shortest routes from home to school of primary school students and how the route distance can be shortened at the household level in Nanjing, China. We found that gated urban form results in significantly roundabout routes to school. In 2016, China issued the Opening and Prohibiting Gated Communities policy, subsequently the Healthy Cities Initiative, etc. which may leverage cities towards more healthy and sustainable transformations. In the light of these policies, we hypothesised that providing through access as management option, and opening new entries as reengineering option, would shorten school travel distance with minor costs. The scenario analysis shows that such management and reengineering adaptions would provide shorter and potentially less exposed routes for students. This study identifies how the existent urban form works against active school travel, and proposes how salutogenic pathways may be created in the gated urban form. The study, with transferability to other cities, can assist urban designers and policy makers in piloting urban (re)form incrementally and pragmatically to prompt active travel to schools.
Frequent genetic alterations in immune checkpoint–related genes in intravascular large B-cell lymphoma
Authors: Shimada Kazuyuki , Yoshida Kenichi , Suzuki Yasuhiro , Iriyama Chisako , Inoue Yoshikage , Sanada Masashi , Kataoka Keisuke , Yuge Masaaki , Takagi Yusuke , Kusumoto Shigeru , Masaki Yasufumi , Ito Takahiko , Inagaki Yuichiro , Okamoto Akinao , Kuwatsuka Yachiyo , Nakatochi Masahiro , Shimada Satoko , Miyoshi Hiroaki , Shiraishi Yuichi , Chiba Kenichi , Tanaka Hiroko , Miyano Satoru , Shiozawa Yusuke , Nannya Yasuhito , Okabe Asako , Kohno Kei , Atsuta Yoshiko , Ohshima Koichi , Nakamura Shigeo , Ogawa Seishi , Tomita Akihiro , Kiyoi Hitoshi
Published: December 2020

Intravascular large B-cell lymphoma (IVLBCL) is a unique type of extranodal lymphoma characterized by selective growth of tumor cells in small vessels without lymphadenopathy. Greater understanding of the molecular pathogenesis of IVLBCL is hampered by the paucity of lymphoma cells in biopsy specimens, creating a limitation in obtaining sufficient tumor materials. To uncover the genetic landscape of IVLBCL, we performed whole-exome sequencing (WES) of 21 patients with IVLBCL using plasma-derived cell-free DNA (cfDNA) (n = 18), patient-derived xenograft tumors (n = 4), and tumor DNA from bone marrow (BM) mononuclear cells (n = 2). The concentration of cfDNA in IVLBCL was significantly higher than that in diffuse large B-cell lymphoma (DLBCL) (P < .0001) and healthy donors (P = .0053), allowing us to perform WES; most mutations detected in BM tumor DNA were successfully captured in cfDNA and xenograft. IVLBCL showed a high frequency of genetic lesions characteristic of activated B-cell–type DLBCL, with the former showing conspicuously higher frequencies (compared with nodal DLBCL) of mutations in MYD88 (57%), CD79B (67%), SETD1B (57%), and HLA-B (57%). We also found that 8 IVLBCL (38%) harbored rearrangements of programmed cell death 1 ligand 1 and 2 (PD-L1/PD-L2) involving the 3′ untranslated region; such rearrangements are implicated in immune evasion via PD-L1/PD-L2 overexpression. Our data demonstrate the utility of cfDNA and imply important roles for immune evasion in IVLBCL pathogenesis and PD-1/PD-L1/PD-L2 blockade in therapeutics for IVLBCL.
Childhood maltreatment and lung function: findings from the general population
Authors: Spitzer Carsten , Ewert Ralf , Völzke Henry , Frenzel Stefan , Felix Stephan B. , Lübke Laura , Grabe Hans J.
Published: December 2020

Objective

Cumulative evidence indicates that childhood maltreatment is linked to self-reported asthma and COPD. However, the relationship between childhood maltreatment and objective measures of lung function as determined by spirometry has not yet been assessed.

Methods

Medical histories and spirometric lung function were taken in 1386 adults from the general population. Participants completed the Childhood Trauma Questionnaire for the assessment of emotional, physical and sexual abuse as well as emotional and physical neglect.

Results

25.3% of the participants reported at least one type of childhood maltreatment. Among them, use of medication for obstructive airway diseases as well as typical signs and symptoms of airflow limitation were significantly more frequent than in the group without exposure to childhood maltreatment. Although participants with childhood maltreatment had numerically lower values for forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC) and peak expiratory flow than those without, these differences were nonsignificant when accounting for relevant covariates such as age, sex, height and smoking. Likewise, there were no differences in the FEV1/FVC ratio nor in the frequency of airflow limitation regardless of its definition. No specific type of childhood maltreatment was related to spirometrically determined parameters of lung function.

Conclusions

Our findings call into question the association of childhood maltreatment with obstructive lung diseases as indicated by prior research relying on self-reported diagnoses. We consider several explanations for these discrepancies.
Viral hepatitis B and C in HIV-exposed South African infants
Authors: Tamandjou Tchuem Cynthia , Cotton Mark Fredric , Nel Etienne , Tedder Richard , Preiser Wolfgang , Violari Avy , Bobat Raziya , Hovind Laura , Aaron Lisa , Montepiedra Grace , Mitchell Charles , Andersson Monique Ingrid
Published: December 2020

Background

Whilst much attention is given to eliminating HIV mother-to-child transmission (MTCT), little has been done to ensure the same for hepatitis B virus (HBV) transmission. The introduction of HBV immunization at six weeks of age has reduced HBV horizontal transmission in South Africa. However, in order to eliminate HBV MTCT, further interventions are needed. The risk of hepatitis C virus (HCV) MTCT in HIV-infected (HIV+) African women is not yet well described. This study aimed to determine the rate of HBV and HCV vertical transmission in HIV-exposed infants in South Africa.

Methods

Serum samples from infants enrolled in an isoniazid prevention study (P1041) were screened for HBV and HCV serology markers; screening was performed on samples collected at approximately 60 weeks of age of the infants. HBV DNA was quantified in HBsAg positive samples and HBV strains characterized through gene sequencing. All HCV antibody samples with inconclusive results underwent molecular testing.

Results

Three of 821 infants were positive for both HBsAg and HBV DNA. All HBV strains belonged to HBV sub-genotype A1. The rtM204I mutation associated with lamivudine resistance was identified in one infant, a second infant harboured the double A1762T/G1764A BCP mutation. Phylogenetic analysis showed clustering between mother and infant viral genomic sequences. Twenty-one of 821 HIV-exposed infants tested had inconclusive HCV antibody results, none were HCV PCR positive.

Conclusions

This study suggests that HBV vertical transmission is likely to be occurring in HIV-exposed infants in South Africa.. A more robust strategy of HBV prevention, including birth dose vaccination, is required to eradicate HBV MTCT. HCV infection was not detected.
Multi-organ point-of-care ultrasound for COVID-19 (PoCUS4COVID): international expert consensus
Authors: Hussain Arif , Via Gabriele , Melniker Lawrence , Goffi Alberto , Tavazzi Guido , Neri Luca , Villen Tomas , Hoppmann Richard , Mojoli Francesco , Noble Vicki , Zieleskiewicz Laurent , Blanco Pablo , Ma Irene W. Y. , Wahab Mahathar Abd. , Alsaawi Abdulmohsen , Al Salamah Majid , Balik Martin , Barca Diego , Bendjelid Karim , Bouhemad Belaid , Bravo-Figueroa Pablo , Breitkreutz Raoul , Calderon Juan , Connolly Jim , Copetti Roberto , Corradi Francesco , Dean Anthony J. , Denault André , Govil Deepak , Graci Carmela , Ha Young-Rock , Hurtado Laura , Kameda Toru , Lanspa Michael , Laursen Christian B. , Lee Francis , Liu Rachel , Meineri Massimiliano , Montorfano Miguel , Nazerian Peiman , Nelson Bret P. , Neskovic Aleksandar N. , Nogue Ramon , Osman Adi , Pazeli José , Pereira-Junior Elmo , Petrovic Tomislav , Pivetta Emanuele , Poelaert Jan , Price Susanna , Prosen Gregor , Rodriguez Shalim , Rola Philippe , Royse Colin , Chen Yale Tung , Wells Mike , Wong Adrian , Xiaoting Wang , Zhen Wang , Arabi Yaseen
Published: December 2020

COVID-19 has caused great devastation in the past year. Multi-organ point-of-care ultrasound (PoCUS) including lung ultrasound (LUS) and focused cardiac ultrasound (FoCUS) as a clinical adjunct has played a significant role in triaging, diagnosis and medical management of COVID-19 patients. The expert panel from 27 countries and 6 continents with considerable experience of direct application of PoCUS on COVID-19 patients presents evidence-based consensus using GRADE methodology for the quality of evidence and an expedited, modified-Delphi process for the strength of expert consensus. The use of ultrasound is suggested in many clinical situations related to respiratory, cardiovascular and thromboembolic aspects of COVID-19, comparing well with other imaging modalities. The limitations due to insufficient data are highlighted as opportunities for future research.
Lack of astrocytes hinders parenchymal oligodendrocyte precursor cells from reaching a myelinating state in osmolyte-induced demyelination
Authors: Lohrberg Melanie , Winkler Anne , Franz Jonas , van der Meer Franziska , Ruhwedel Torben , Sirmpilatze Nikoloz , Dadarwal Rakshit , Handwerker Ronja , Esser Daniel , Wiegand Kerstin , Hagel Christian , Gocht Andreas , König Fatima Barbara , Boretius Susann , Möbius Wiebke , Stadelmann Christine , Barrantes-Freer Alonso
Published: December 2020

Demyelinated lesions in human pons observed after osmotic shifts in serum have been referred to as central pontine myelinolysis (CPM). Astrocytic damage, which is prominent in neuroinflammatory diseases like neuromyelitis optica (NMO) and multiple sclerosis (MS), is considered the primary event during formation of CPM lesions. Although more data on the effects of astrocyte-derived factors on oligodendrocyte precursor cells (OPCs) and remyelination are emerging, still little is known about remyelination of lesions with primary astrocytic loss. In autopsy tissue from patients with CPM as well as in an experimental model, we were able to characterize OPC activation and differentiation. Injections of the thymidine-analogue BrdU traced the maturation of OPCs activated in early astrocyte-depleted lesions. We observed rapid activation of the parenchymal NG2+ OPC reservoir in experimental astrocyte-depleted demyelinated lesions, leading to extensive OPC proliferation. One week after lesion initiation, most parenchyma-derived OPCs expressed breast carcinoma amplified sequence-1 (BCAS1), indicating the transition into a pre-myelinating state. Cells derived from this early parenchymal response often presented a dysfunctional morphology with condensed cytoplasm and few extending processes, and were only sparsely detected among myelin-producing or mature oligodendrocytes. Correspondingly, early stages of human CPM lesions also showed reduced astrocyte numbers and non-myelinating BCAS1+ oligodendrocytes with dysfunctional morphology. In the rat model, neural stem cells (NSCs) located in the subventricular zone (SVZ) were activated while the lesion was already partially repopulated with OPCs, giving rise to nestin+ progenitors that generated oligodendroglial lineage cells in the lesion, which was successively repopulated with astrocytes and remyelinated. These nestin+ stem cell-derived progenitors were absent in human CPM cases, which may have contributed to the inefficient lesion repair. The present study points to the importance of astrocyte-oligodendrocyte interactions for remyelination, highlighting the necessity to further determine the impact of astrocyte dysfunction on remyelination inefficiency in demyelinating disorders including MS.
Mineral composition of beetroot treated with potential elicitors and inoculated with Meloidogyne javanica
Authors: Débia Paula Juliana Grotto , Bolanho Beatriz Cervejeira , Dias-Arieira Claudia Regina
Published: December 2020

Background

The root-knot nematode Meloidogyne javanica can infect beetroots, causing extensive damage to this food crop. As chemical and genetic control tactics have shown limited efficacy, new strategies are needed to improve the integrated management of this parasite. This study assessed the influence of potential defence elicitors and M. javanica infection on the mineral composition of beetroot. Plants were treated with acibenzolar-S-methyl (ASM), citrus biomass, or a mannanoligosaccharide-based product (MOS) and inoculated with 1000 eggs and second-stage juveniles of M. javanica. At 60 days after inoculation, beetroot plants were harvested and evaluated for nematode population density, vegetative growth, and mineral content.

Results

All potential elicitors reduced nematode population density in beetroots (p ≤ 0.10) and improved the vegetative parameters of inoculated plants (p ≤ 0.05), except shoot fresh weight. Some minerals were found to be negatively affected by treatments, particularly calcium, whose levels were consistently lower in treated plants. On the other hand, M. javanica inoculation increased magnesium, iron, manganese, zinc, and copper contents in beetroots. However, the latter mineral (Cu content) of inoculated plants was positively influenced by MOS and ASM.

Conclusion

Potential elicitor treatments did not improve the mineral composition of beetroot, but were effective in reducing nematode population density. Plants inoculated with M. javanica had higher mineral levels. However, gall formation decreases the commercial value of the crop and might render it unsuitable for commercialisation. M. javanica-infected beetroots may be used for nutrient extraction or sold to food processing industries.
The fungal sexual revolution continues: discovery of sexual development in members of the genus Aspergillus and its consequences
Authors: Ellena Valeria , Sauer Michael , Steiger Matthias G.
Published: December 2020

Asexuality was considered to be a common feature of a large part of fungi, including those of the genusAspergillus. However, recent advances and the available genomic and genetic engineering technologies allowed to gather more and more indications of a hidden sexuality in fungi previously considered asexual. In parallel, the acquired knowledge of the most suitable conditions for crossings was shown to be crucial to effectively promote sexual reproduction in the laboratory. These discoveries not only have consequences on our knowledge of the biological processes ongoing in nature, questioning if truly asexual fungal species exist, but they also have important implications on other research areas. For instance, the presence of sexuality in certain fungi can have effects on their pathogenicity or on shaping the ecosystem that they normally colonize. For these reasons, further investigations of the sexual potential ofAspergillusspecies, such as the industrially importantA. niger, will be carried on.
Seismic denoising via truncated nuclear norm minimization
Authors: Shao Ouyang , Wang Lingling , Hu Xiangyun , Long Zhidan
Published: December 2020

Because there are many similar geologic structures underground, seismic profiles have an abundance of self-repeating patterns. Thus, we can divide a seismic profile into groups of blocks with a similar seismic structure. The matrix formed by stacking together similar blocks in each group should be of low rank. Hence, we can transfer the seismic denoising problem to a series of low-rank matrix approximation (LRMA) problems. The LRMA-based model commonly adopts the nuclear norm as a convex substitute of the rank of a matrix. However, the nuclear norm minimization (NNM) shrinks the different rank components equally and may cause some biases in practice. The recently introduced truncated nuclear norm (TNN) has been proven to more accurately approximate the rank of a matrix, which is given by the sum of the set of the smallest singular values. Based on this, we have adopted a novel denoising method using truncated nuclear norm minimization (TNNM). The objective function of this method consists of two terms, the F-norm data fidelity and a TNN regularization. We develop an efficient two-step iterative algorithm to solve this objective function. Then, we apply the proposed TNNM algorithm to groups of blocks with similar seismic structure, and we aggregate all resulting denoised blocks to get the denoised seismic data. We update the denoised results during each iteration to gradually attenuate the heavy noise. Numerical experiments demonstrate that, compared with f-x deconvolution and the curvelet- and NNM-based methods, TNNM not only attenuates noise more effectively even when the signal-to-noise ratio is as low as −10 dB and seismic data have complex structures, but it also accurately preserves the seismic structures without inducing Gibbs artifacts.
Lacustrine mixed siliciclastic-carbonate sedimentary rocks in the Paleogene Funing Formation of the Subei Basin, eastern China: Characteristics and origin
Authors: Li Wei , Zhu Xiaomin , Liu Qidong , Zhu Shifa , Li Heyong
Published: December 2020

The study of sedimentary characteristics and genetic mechanism of mixed siliciclastic-carbonate sediments (MSCSs) is not only the focus of sedimentary geology, but it is also an important issue in petroleum exploration and development. We have discovered the lacustrine MSCSs, the interstratified siliciclastic-carbonate sediments and the textural mixture of siliciclastic and carbonate materials (s-MSCSs) in the second member of the Paleogene Funing Formation ([Formula: see text]) in the Gaoyou and Jinhu sags, Subei Basin, eastern China. We use core, mud-log and thin-section data to clarify the [Formula: see text] s-MSCSs into five types, and we also use geochemical data of the [Formula: see text] mudstone including X-ray diffraction (XRD) whole rock, XRD clay, and trace elements to quantitatively analyze lake paleosalinity. The [Formula: see text] s-MSCSs mainly consist of siliciclasts, ooids, intraclasts, and mud, and they could be siliciclast-dominated, allochem-dominated, or without dominant components. We analyze that mixed sediments occur under either traction flow or gravity flow. The s-MSCSs of the traction flow origin develop small-scale, wavy cross-bedding and consist of siliciclasts and ooids of similar size; the s-MSCSs of the gravity flow origin develop massive bedding and graded bedding with complex lithology, and they mainly consist of siliciclasts and allochems of different size. We hypothesize that the increase of lake paleosalinity controlled by the climate and the moderate siliciclast influx under stable tectonic setting provide the material source for s-MSCSs in the lacustrine basin. Multidirectional flow is common during the deposition of s-MSCSs of traction flow origin, and seasonal flooding produces s-MSCSs of the gravity flow origin. Lacustrine s-MSCSs in the Gaoyou and Jinhu sags have significantly smaller scale and quantity, and ooids rather than bioclasts occupy most of the carbonate components.
Population Pharmacodynamic Modeling Using the Sigmoid Emax Model: Influence of Inter-individual Variability on the Steepness of the Concentration–Effect Relationship. a Simulation Study
Authors: Proost Johannes H. , Eleveld Douglas J. , Struys Michel M. R. F.
Published: December 2020

The relationship between the concentration of a drug and its pharmacological effect is often described by empirical mathematical models. We investigated the relationship between the steepness of the concentration–effect relationship and inter-individual variability (IIV) of the parameters of the sigmoid Emax model, using the similarity between the sigmoid Emax model and the cumulative log-normal distribution. In addition, it is investigated whether IIV in the model parameters can be estimated accurately by population modeling. Multiple data sets, consisting of 40 individuals with 4 binary observations in each individual, were simulated with varying values for the model parameters and their IIV. The data sets were analyzed using Excel Solver and NONMEM. An empirical equation (Eq. (11)) was derived describing the steepness of the population-predicted concentration–effect profile (γ*) as a function of γ and IIV in C50 and γ, and was validated for both binary and continuous data. The tested study design is not suited to estimate the IIV in C50 and γ with reasonable precision. Using a naive pooling procedure, the population estimates γ* are significantly lower than the value of γ used for simulation. The steepness of the population-predicted concentration–effect relationship (γ*) is less than that of the individuals (γ). Using γ*, the population-predicted drug effect represents the drug effect, for binary data the probability of drug effect, at a given concentration for an arbitrary individual.
Expandability of the Covalent Bond: A New Facet Discovered in Extremely Long Csp3-Csp3 Single Bonds
Authors: Ishigaki Yusuke , Uchimura Yasuto , Shimajiri Takuya , Suzuki Takanori
Published: December 2020

Molecules with an extreme structural parameter, such as an elongated C-C bond, have attracted much attention due to their special properties, which ordinary molecules do not have. Stabilized hexaphenylethanes are suitable compounds for seeking for the longest C-C bond. In addition to steric repulsion among the aryl groups (“front strain”) found in 1,1,2,2-tetraarylacenaphthenes (1), “scissor effects” cause expansion of the C1-C2 bond in 1,1,2,2-tetraarylpyracenes (2). A series of crystallographic analyses of 2 revealed that the substituent on the aryl group also affects the C1-C2 bond length. The “front strain” over the weakened bond is enhanced by the ring-fused structure in di(spiroacridan)pyracene (2A). The bond length of 1.771(3) Å determined by X-ray analysis at 93 K is one of the largest values for a Csp3-Csp3 bond, and increases to 1.791(3) Å when the single crystal is heated to 413 K. Further expansion over 1.80 Å was achieved by maximizing the front strain by fixing the spirodibenzocycloheptatriene units in an eclipsed manner in the core-shell-type dihydropyracylene (3B) [1.795(2) Å at 100 K, 1.806(2) Å at 400 K]. Several studies show that “bond expandability” is a newly discovered feature of an elongated covalent bond, which could be used for the future design of novel materials with a mechanical/thermal response.
СВАДЕБНЫЙ ФОЛЬКЛОР УКРАИНЦЕВ РЕСПУБЛИКИ БАШКОРТОСТАН КАК ФАКТОР ЭТНИЧЕСКОЙ ИДЕНТИЧНОСТИ
Authors: Pylypak Maksym Anatolevich
Published: December 2020

Целью статьи является анализ свадебного фольклора украинцев Республики Башкортостан, как одного из факторов сохранения этнической идентичности.Методы и методология проведения работы. В исследовании использованы метод стороннего наблюдения, метод опроса, историко-сравнительный метод.Результаты. Выявлено, что традиционная свадьба украинцев Республики Башкортостан в процессе их длительного проживания в условиях полиэтничной среды, существенно трансформировалась. Отмечается прямая зависимость уровня наполнения фольклорными текстами каждого из этапов свадьбы от уровня сохранения ее структуры.Основными причинами сокращения продолжительности свадьбы стали плохое материальное положение в послевоенное время, появление межнациональных браков, смена места ее празднования, а также ряд нововведений.На современном этапе исследования спорадически зафиксировано бытование ритуальных, корильных (песен-насмешек), величальных свадебных песен, что свидетельствует о сохранении украинцами этнической идентичности.Область применения результатов. Результаты исследования могут быть применены в научно-исследовательской работе и образовательном процессе.