bluuebunny/crossref_metadata_2025 huggingface dataset:
Worldwide poliomyelitis outbreaks: should mass gathering organizers be concerned?
Authors: Al-Tawfiq Jaffar A , Kattan Rana F , Almoallem Saleh Abdullah S , Altawfiq Kauthar J , Mohsni Ezzeddine , Memish Ziad A
Published: November 2022

The polio is the longest PHEIC and the continued occurrence of outbreaks of cVDPV would put further risks globally. The binary nature of PHEIC declarations would not support the continued polio PHEIC due to the requirement of tiered or graded strategies to combat such diseases.
Mycoplasma haemohominis as a cause of fever of unknown origin in a traveller
Authors: Klement-Frutos Elise , Mediannikov Oleg , Fournier Pierre-Edouard , Haroche Julien , Leblond Véronique , Caumes Eric
Published: November 2022

Candidatus mycoplasma haemohominis (cMh) is the most human-adapted and lethal haemoplasma. Bats are the common reservoir worldwide. cMh should be suspected in fever of unknown origin associated with splenomegaly, and haemolytic anaemia or haemophagocytic lymphohistiocytosis, above all in Asia Pacific travellers. Doxycycline should  be started preemptively as diagnosis can be retrospectively confirmed.
Burden ofShigellain South Asia: a systematic review and meta-analysis
Authors: Muzembo Basilua Andre , Kitahara Kei , Mitra Debmalya , Ohno Ayumu , Khatiwada Januka , Dutta Shanta , Miyoshi Shin-Ichi
Published: November 2022

Background

Shigella remains one of the most common causes of diarrhoea in South Asia. Current estimates of the prevalence of Shigella are critical for guiding control measures. We estimated the prevalence of Shigella species and serogroups in South Asia.

Methods

We performed a systematic review using PubMed, EMBASE, Google Scholar and Web of Science for peer-reviewed studies published between 2000 and 19 June 2022. We also manually searched the reference lists of the reviewed studies to identify additional studies. We included studies that detected the presence of Shigella in stool by culture or polymerase chain reaction (PCR). Studies associated with outbreaks were excluded. Two investigators independently reviewed the studies, extracted the data and performed quality assessment. A random-effects meta-analysis was performed to determine the pooled prevalence of Shigella.

Results

Our search yielded 5707 studies, of which 91 studies from five South Asian countries were included in the systematic review, 79 in the meta-analysis of Shigella prevalence and 63 in the meta-analysis of Shigella serogroups prevalence. The pooled prevalence of Shigella was 7% [95% confidence interval (CI): 6–7%], with heterogeneity (I2 = 98.7; P < 0.01). The prevalence of Shigella was higher in children aged <5 years (10%; 95% CI: 8–11%), in rural areas (12%; 95% CI: 10–14%) and in studies using PCR (15%; 95% CI: 11–19%).

Shigella flexneri (58%) was the most abundant serogroup, followed by Shigella sonnei (19%), Shigella boydii (10%) and Shigella dysenteriae (9%). Shigella flexneri 2a was the most frequently isolated serotype (36%), followed by serotype 3a (12%), serotype 6 (12%) and serotype 1b (6%). The prevalence of non-typeable Shigella was 10.0%.

Conclusions

Although the prevalence of Shigella in South Asia remains generally high, it varies by age group and geographical area, with data lacking in some countries. Effective Shigella vaccines would be advantageous for both endemic communities and travellers.
Nestin prevents mesenchymal stromal cells from apoptosis in LPS-induced lung injury via inhibition of unfolded protein response sensor IRE1α
Authors: Wang Hongmiao , Jiang Chenhao , Cai Jianye , Lu Qiying , Qiu Yuan , Wang Yi , Huang Yinong , Xiao Yong , Wang Boyan , Wei Xiaoyue , Shi Jiahao , Lai Xingqiang , Wang Tao , Wang Jiancheng , Xiang Andy Peng
Published: November 2022

The clinical applications of MSC therapy have been intensely investigated in acute respiratory distress syndrome. However, clinical studies have fallen short of expectations despite encouraging preclinical results. One of the key problems is that transplanted stem cells can hardly survive in the harsh inflammatory environment. Prolonging the survival of transplanted MSCs might be a promising strategy to enhance the therapeutic efficacy of MSC therapy. Here, we identified Nestin, a class VI intermediate filament, as a positive regulator of MSC survival in the inflammatory microenvironment. We showed that Nestin knockout led to a significant increase of MSC apoptosis, which hampered the therapeutic effects in an LPS-induced lung injury model. Mechanistically, Nestin knockout induced a significant elevation of endoplasmic reticulum (ER) stress level. Further investigations showed that Nestin could bind to IRE1α and inhibit ER stress-induced apoptosis under stress. Furthermore, pretreatment with IRE1α inhibitor 4μ8C improved MSC survival and improved therapeutic effect. Our data suggests that Nestin enhances stem cell survival after transplantation by inhibiting ER stress-induced apoptosis, improving protection, and repair of the lung inflammatory injury.
Prostate cancer resistance leads to a global deregulation of translation factors and unconventional translation
Authors: Lelong Emeline I J , Khelifi Gabriel , Adjibade Pauline , Joncas France-Hélène , Grenier St-Sauveur Valérie , Paquette Virginie , Gris Typhaine , Zoubeidi Amina , Audet-Walsh Etienne , Lambert Jean-Philippe , Toren Paul , Mazroui Rachid , Hussein Samer M I
Published: November 2022

Emerging evidence associates translation factors and regulators to tumorigenesis. However, our understanding of translational changes in cancer resistance is still limited. Here, we generated an enzalutamide-resistant prostate cancer (PCa) model, which recapitulated key features of clinical enzalutamide-resistant PCa. Using this model and poly(ribo)some profiling, we investigated global translation changes that occur during acquisition of PCa resistance. We found that enzalutamide-resistant cells exhibit an overall decrease in mRNA translation with a specific deregulation in the abundance of proteins involved in mitochondrial processes and in translational regulation. However, several mRNAs escape this translational downregulation and are nonetheless bound to heavy polysomes in enzalutamide-resistant cells suggesting active translation. Moreover, expressing these corresponding genes in enzalutamide-sensitive cells promotes resistance to enzalutamide treatment. We also found increased association of long non-coding RNAs (lncRNAs) with heavy polysomes in enzalutamide-resistant cells, suggesting that some lncRNAs are actively translated during enzalutamide resistance. Consistent with these findings, expressing the predicted coding sequences of known lncRNAs JPX, CRNDE and LINC00467 in enzalutamide-sensitive cells drove resistance to enzalutamide. Taken together, this suggests that aberrant translation of specific mRNAs and lncRNAs is a strong indicator of PCa enzalutamide resistance, which points towards novel therapeutic avenues that may target enzalutamide-resistant PCa.
Randomized phase III study of high-dose methotrexate and whole-brain radiotherapy with/without temozolomide for newly diagnosed primary CNS lymphoma: JCOG1114C
Authors: Mishima Kazuhiko , Nishikawa Ryo , Narita Yoshitaka , Mizusawa Junki , Sumi Minako , Koga Tomoyuki , Sasaki Nobuyoshi , Kinoshita Manabu , Nagane Motoo , Arakawa Yoshiki , Yoshimoto Koji , Shibahara Ichiyo , Shinojima Naoki , Asano Kenichiro , Tsurubuchi Takao , Sasaki Hikaru , Asai Akio , Sasayama Takashi , Momii Yasutomo , Sasaki Atsushi , Nakamura Shigeo , Kojima Masaru , Tamaru Jun-ichi , Tsuchiya Kazuhiro , Gomyo Miho , Abe Kayoko , Natsumeda Manabu , Yamasaki Fumiyuki , Katayama Hiroshi , Fukuda Haruhiko
Published: November 2022

Background

The goal was to determine whether the addition of temozolomide (TMZ) to the standard treatment of high-dose methotrexate (HD-MTX) and whole-brain radiotherapy (WBRT) for primary central nervous system lymphoma (PCNSL) improves survival.

Methods

An open-label, randomized, phase III trial was conducted in Japan, enrolling immunocompetent patients aged 20–70 years with histologically confirmed, newly diagnosed PCNSL. After administration of HD-MTX, patients were randomly assigned to receive WBRT (30 Gy) ± 10 Gy boost (arm A) or WBRT ± boost with concomitant and maintenance TMZ for 2 years (arm B). The primary endpoint was overall survival (OS).

Results

Between September 29, 2014 and October 15, 2018, 134 patients were enrolled, of whom 122 were randomly assigned and analyzed. At the planned interim analysis, 2-year OS was 86.8% (95% confidence interval [CI]: 72.5–94.0%) in arm A and 71.4% (56.0–82.2%) in arm B. The hazard ratio was 2.18 (95% CI: 0.95–4.98), with the predicted probability of showing the superiority of arm B at the final analysis estimated to be 1.3%. The study was terminated early due to futility. O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation status was measured in 115 tumors, and it was neither prognostic nor predictive of TMZ response.

Conclusions

This study failed to demonstrate the benefit of concomitant and maintenance TMZ in newly diagnosed PCNSL.
Brain Aging and Alzheimer’s Disease in Down Syndrome
Authors: Helman Alex , Van Pelt Kathryn , Schmitt Frederick A. , Head Elizabeth
Published: November 2022

People with Down syndrome (DS) are vulnerable to Alzheimer disease (AD), particularly over the age of 40 years due to the extra copy of chromosome 21 in the most common form of DS. Despite the prevalence of AD in people with DS, there are few clinical trials for people with DS. This gap highlights that persons with DS comprise an underserved, vulnerable population who develop AD neuropathology at an early age. This article reviews AD neuropathology in persons with DS and key genes associated with DS that are also thought to play a role in AD development. The potential roles of inflammation, cerebrovascular pathology, and white matter changes are also reviewed. Gaps in our understanding of AD in persons with DS and promising areas of investigation are identified. It will be critical to better understand the age-dependency of AD- associated events in persons with DS to identify novel targets for intervention and to determine the ages at which these pathways may be most modifiable.
Bureaucracy and Public Administration
Authors: Tavares António F.
Published: November 2022

This chapter aims to provide an overview of Portuguese public administration and highlight the current challenges it faces as the entity responsible for organizing and providing public services. The chapter begins with a description of the ‘administrative state model’ which has prevailed in Portuguese public administration during the twentieth century. This is followed by a discussion on the late influence of the New Public Management movement of administrative reforms and the complex mix of legal and managerial traits which resulted from these changes over the past four decades. The chapter offers some evidence of the impact of these reforms on citizen perceptions of public service delivery, underlining the role of technological innovation as a key enabler of administrative modernization and democratization. The chapter ends with suggestions of possible directions for future research about Portuguese Public Administration.
Decentralization and Local Politics
Authors: Teles Filipe
Published: November 2022

This chapter explores the most recent developments in Portuguese local politics. The role of local governments, their evolution and reform trends in Europe will set the comparative background for this chapter and will provide the analytical tools needed to understand different perspectives and the debates regarding decentralization, municipal autonomy and multilevel governance in Portugal. The pace and alternative paths of reforms in most countries have underlined the relevance of reorganizing local jurisdictions, mainly given the growing complexity of their governance arrangements and their fragmentation. By briefly explaining the main European challenges, especially the territorial and functional reforms of the last decades, while putting into perspective these key debates in Portugal, it will be possible to identify the main questions under debate. By trying to establish a future research agenda, this chapter is also aiming to keep these debates alive.
Election Campaigns
Authors: Santana-Pereira José
Published: November 2022

This chapter discusses the nature of election campaigns in Portugal, framing them within the general scholarly debates about campaigning. Portuguese campaigns can be described as highly party-centric, centralized, and poorly professionalized, often focusing on responsibility for outcomes in first-order elections and domestic issues in European Parliament elections. Negative campaigns are seldom carried out. In terms of channels, Portuguese campaigns are primarily based on traditional media, online resources are scarcely used, and a business-as-usual pattern in terms of online party competition is often observed. Election campaigns in Portugal are covered in generally neutral terms by the media being frequently framed by them in strategic and conflictive terms. Not much is known about the effects of campaigns in the country. The chapter ends with thematic and methodological suggestions for future research on campaigning in Portugal.
The Portuguese Welfare State
Authors: Glatzer Miguel , Moreira Amílcar
Published: November 2022

This chapter provides an overview of the key features and trends that shape the Portuguese Welfare State (PTWS). It starts by discussing how the PTWS developed into its current institutional design, and how it compares with alternative models of welfare provision in other advanced economies. We then examine the processes of institutional change over the last two decades. Here we show that, up to the end of the Sovereign Debt Crisis (2011–2014), consecutive governments pursued policies to deregulate the labour market and to contain the growth of social expenditure. This focus on deregulation and cost-containment was, however, punctuated by efforts to expand (albeit in a very targeted way) and recalibrate social protection. We also show that the policy reversals after 2015, while representing a clear break from the internal devaluation agenda pursued during the troika years, do not necessarily mean the pursuit of a new model of social protection. We further argue that this process of institutional change is fundamentally shaped by dynamics of partisan competition and multilevel governance. Moving beyond the focus on the dynamics of institutional change, the last section examines the role of the PTWS in redistributing economic opportunities across Portuguese society. Building on these findings, we conclude with a set of suggestions for future research on the PTWS.
Health Policies
Authors: Mateus Céu
Published: November 2022

The Portuguese National Health Service (NHS) was created in 1979 and, like England’s NHS, it was universal in coverage, free at the point of use, and financed through taxation. It represented a major change in the way healthcare services were organized and delivered in Portugal, as it marked a shift from a Bismarckian perspective to a Bevanite one. This chapter aims to explain how the tensions between the features in both systems have been dealt with. What has been the role of private healthcare provision? What is the burden of out-of-pocket payments in households’ expenditures? Has equal access to care been achieved, as stated in the legislation? Were the driving forces behind major reforms based on evidence, or were we just following on others’ footsteps?
Bailout Politics in Portugal (2008–2020)
Authors: Moury Catherine , De Giorgi Elisabetta
Published: November 2022

In 2011, Portugal was one of the countries that were most dramatically hit by the emerging Eurozone crisis. As its cost of borrowing rose dramatically, the country faced both a political and an economic crisis, resulting in the fall of the government and in requesting a bailout. This bailout was conditional on Portugal undertaking public spending cuts and structural reforms across numerous sectors. In this chapter we show that, during this period, the Portuguese government had some room for manoeuvre to advocate for new policies, and to resist, shape or roll back some of the policies demanded by external actors. We also provide some examples of times when domestic actors were able to exploit the constraint of conditionality to their own advantage. The chapter concludes by looking at what happened after the bailout and showing that Portuguese governments could use their discretion to reverse measures in order to attain the greatest benefits at a lower cost.
Portuguese Foreign Policy
Authors: Freire Maria Raquel
Published: November 2022

Portugal has a remarkably complex foreign policy, balancing the demands of transatlantic relations, including the Atlantic Alliance; European commitments within the European Union; and deep cultural and economic ties with former colonies within different multilateral and bilateral frameworks. This chapter analyses the evolution and main lines adopted in Portuguese foreign policy, making three points. Firstly, with the country’s transition from dictatorship to democracy, foreign policy experienced a fundamental shift, and currently follows a principled and pragmatic line of action, whereby values-oriented approaches are informed by the country’s identity construct; secondly, foreign policy is multi-layered, which brings nuances to foreign policy alignments beyond the traditional triangular thematic focus; and thirdly, there have been efforts to turn what could be adverse factors into opportunities, thus ‘squaring the circle’ in Portuguese external relations. The chapter concludes by identifying future avenues for research.
Portugal and Brazil
Authors: Malamud Andrés , Seabra Pedro
Published: November 2022

Relations between Portugal and Brazil are often characterized as much by political ambiguity as by a rhetoric that oscillates between fraternity in public speech, and condescendence in private conversation. These features can be found at the core of every advance and obstacle in the institutionalization of this bilateral relationship, and they help to explain the particularities of the political bond between Lisbon and Rio (initially) or Brasília (later). This chapter compares parallel political developments within both countries and highlights points of contention and attraction between the two countries. The chapter is divided chronologically into four sections: colonial rule; the Estado Novo regimes; the end of both dictatorships; and the democratic period. By exploring contrasts, similarities and reciprocal influences, we suggest that historical linkages have worked as a buffer rather than a driver towards a substantive common agenda.
RNA-binding protein MAC5A interacts with the 26S proteasome to regulate DNA damage response in Arabidopsis
Authors: Meng Xiangxiang , Wang Quanhui , Hao Ruili , Li Xudong , Li Mu , Hu Ruibo , Du Hai , Hu Zhubing , Yu Bin , Li Shengjun
Published: November 2022

DNA damage response (DDR) in eukaryotes is essential for the maintenance of genome integrity in challenging environments. The regulatory mechanisms of DDR have been well-established in yeast and humans. However, increasing evidence supports the idea that plants seem to employ different signaling pathways that remain largely unknown. Here, we report the role of MODIFIER OF SNC1, 4-ASSOCIATED COMPLEX SUBUNIT 5A (MAC5A) in DDR in Arabidopsis (Arabidopsis thaliana). Lack of MAC5A in mac5a mutants causes hypersensitive phenotypes to methyl methanesulfonate (MMS), a DNA damage inducer. Consistent with this observation, MAC5A can regulate alternative splicing of DDR genes to maintain the proper response to genotoxic stress. Interestingly, MAC5A interacts with the 26S proteasome (26SP) and is required for its proteasome activity. MAC core subunits are also involved in MMS-induced DDR. Moreover, we find that MAC5A, the MAC core subunits, and 26SP may act collaboratively to mediate high-boron-induced growth repression through DDR. Collectively, our findings uncover the crucial role of MAC in MMS-induced DDR in orchestrating growth and stress adaptation in plants.
Latitudinal shifts of soil microbial biomass seasonality
Authors: Zhao Fazhu , He Liyuan , Bond-Lamberty Ben , Janssens Ivan A , Wang Jieying , Pang Guowei , Wu Yuwei , Xu Xiaofeng
Published: November 2022

Soil microbes ultimately drive the mineralization of soil organic carbon and thus ecosystem functions. We compiled a dataset of the seasonality of microbial biomass carbon (MBC) and developed a semi-mechanistic model to map monthly MBC across the globe. MBC exhibits an equatorially symmetric seasonality between the Northern and Southern Hemispheres. In the Northern Hemisphere, MBC peaks in autumn and is minimal in spring at low latitudes (<25°N), peaks in the spring and is minimal in autumn at mid-latitudes (25°N to 50°N), while peaks in autumn and is minimal in spring at high latitudes (>50°N). This latitudinal shift of MBC seasonality is attributed to an interaction of soil temperature, soil moisture, and substrate availability. The MBC seasonality is inconsistent with patterns of heterotrophic respiration, indicating that MBC as a proxy for microbial activity is inappropriate at this resolution. This study highlights the need to explicitly represent microbial physiology in microbial models. The interactive controls of environments and substrate on microbial seasonality provide insights for better representing microbial mechanisms in simulating ecosystem functions at the seasonal scale.
CCL24, CXCL9 and CXCL10 are increased in synovial fluid in patients with juvenile idiopathic arthritis requiring advanced treatment
Authors: Al-Jaberi Lina , Simonds Megan M , Brescia Anne Marie C
Published: November 2022

Objective

Oligoarticular JIA disease progression and outcomes are variable. Our objective is to detect protein markers that would allow for earlier intervention to potentially halt disease progression. In this retrospective study of serial SF samples, elevated expression of CCL24, CXCL9 and CXCL10 was linked to the eventual need for advanced medications.

Methods

Serial SF samples were selected from patients with persistent and extended oligoarticular JIA. The samples were separated into two groups: those who did and did not receive advanced medications throughout their disease course. Protein antibody arrays and Luminex assays were performed to determine changes in protein expression.

Results

CCL24, CXCL9 and CXCL10 expression levels were significantly higher in patients who eventually required advanced treatment than in those who did not. The expression levels of CCL24 and CXCL9 were consistently elevated in paired samples of those who later received advanced medications. In the persistent oligoarticular JIA group, CXCL10 levels remained elevated over time in those who required advanced treatment. Conversely, CCL24 levels decreased in patients who did not require advanced treatment. In the extended samples, the levels of CCL24 and CXCL10 expression increased significantly over time in the patients who ultimately required advanced treatment.

Conclusion

In patients with oligoarticular JIA, regardless of disease onset and progression, the consistent elevation of any or all three markers, the CCL24, CXCL9 and CXCL10 in SFs was associated with the future use of advanced therapy, which could be reflective of disease severity.
A Theory of the Nominal Character of Stock Securities
Authors: Dumas Bernard , Savioz Marcel
Published: November 2022

We construct recursive solutions for, and study the properties of the dynamic equilibrium of an economy with three types of agents: (i) household/investors who supply labor with a finite elasticity, consume a large variety of goods that are not perfect substitutes and trade government bonds; (ii) firms that produce those varieties of goods, receive productivity shocks and set prices in a Calvo manner; (iii) a government that collects an income-driven fiscal surplus and acts mechanically, buying and selling bonds in accordance with a Taylor policy rule based on expected inflation. In this setting, we show that stock market returns are much less than one-for-one related to inflation over a 1-year holding period, which means that stock securities have a strong nominal character. We also show that their nominal character diminishes as the length of the stock-holding period increases, in accordance with empirical evidence.
Policy-making and evaluation of gender equality programmes: Context, power, and resistance in the transformation process
Authors: Kalpazidou Schmidt Evanthia , Palmén Rachel , Bührer Susanne
Published: November 2022

Through exploring the links between policy, evaluation, and gender, using a gender-transformative lens, this article sheds light on policy and evaluation processes of gender equality programmes, such as the political nature of evaluation and power configurations, involving resistance in the change process. Two case studies of gender equality programmes are visited to explore the links between gender policy implementation in specific contexts, and power configurations and resistance as key factors in both implementation and evaluation. We benefitted from the theoretical insights of both the feminist and the theory of change approaches, which helped us to bridge the boundaries between policy, gender scholarship, and evaluation and allowed us to reflect upon systemic factors and underlying mechanisms that are either facilitating or hindering transformation. This article highlights the benefits of applying such an evaluation framework and demonstrates why factoring in power and resistance to evaluations of gender equality programmes is necessary to explain successes or failures.
An arrayed CRISPR screen reveals Myc depletion to increase productivity of difficult-to-express complex antibodies in CHO cells
Authors: Bauer Niels , Oswald Benedikt , Eiche Maximilian , Schiller Lisa , Langguth Emma , Schantz Christian , Osterlehner Andrea , Shen Amy , Misaghi Shahram , Stingele Julian , Ausländer Simon
Published: November 2022

Complex therapeutic antibody formats, such as bispecifics (bsAbs) or cytokine fusions, may provide new treatment options in diverse disease areas. However, the manufacturing yield of these complex antibody formats in Chinese Hamster Ovary (CHO) cells is lower than monoclonal antibodies due to challenges in expression levels and potential formation of side products. To overcome these limitations, we performed a clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR associated protein 9 (Cas9)-based knockout (KO) arrayed screening of 187 target genes in two CHO clones expressing two different complex antibody formats in a production-mimicking set-up. Our findings revealed that Myc depletion drastically increased product expression (>40%) by enhancing cell-specific productivity. The Myc-depleted cells displayed decreased cell densities together with substantially higher product titers in industrially-relevant bioprocesses using ambr15 and ambr250 bioreactors. Similar effects were observed across multiple different clones, each expressing a distinct complex antibody format. Our findings reinforce the mutually exclusive relationship between growth and production phenotypes and provide a targeted cell engineering approach to impact productivity without impairing product quality. We anticipate that CRISPR/Cas9-based CHO host cell engineering will transform our ability to increase manufacturing yield of high-value complex biotherapeutics.
Phenotypically abnormal cotyledonaryVitis viniferaembryos differ in anatomy, endogenous hormone levels and transcriptome profiles
Authors: Ya Rong , Li Junduo , Zhang Ningbo , Yu Qinhan , Xu Weirong
Published: November 2022

In many perennial fruit species, including grapevine (Vitis vinifera L.), the highly complex process of somatic embryogenesis (SE) can result in the formation of a deformed embryo, although the underlying reasons are still poorly understood. Here, V. vinifera cv. ‘Chardonnay’ cotyledonary embryos with distinct morphologies were used to address this issue. Normal cotyledonary embryos (NCEs) and elongated cotyledonary embryos (ECEs) were observed to have better-developed vasculature and shoot meristems than the vitrified cotyledonary embryos (VCEs) and fused cotyledonary embryos (FCEs), but ECEs were less developed. We determined that the morphological differences in these phenotypically abnormal embryos were likely associated with endogenous hormone levels, since concentrations of the phytohormones indoleacetic acid (IAA) and abscisic acid (ABA) in NCEs were higher than in the other three types. Comparative transcriptome analysis revealed large differences in gene expression of the hormone signaling pathways in normal and abnormal cotyledonary embryos. Weighted gene co-expression network analysis of the different cotyledonary types allowed the identification of co-regulated gene modules associated with SE, suggesting a role for ERF family genes and other transcription factors (TFs) in regulating morphology. Moreover, an analysis of morphology-specific gene expression indicated that the activation of a specific protein kinase, small heat shock proteins (sHSPs) and certain TFs was closely associated with the formation of normal cotyledonary embryos. Our comparative analyses provide insights into the gene networks regulating somatic cotyledon development and open new avenues for research into plant regeneration and functional genomic studies of malformed embryos.
Crop Host Influences on Outcomes of Competition Between Aspergillus Section Flavi Species Coinfecting Maize and Groundnuts
Authors: Ching'anda Connel , Bandyopadhyay Ranajit , Callicott Kenneth , Orbach Marc J. , Cotty Peter J. , Mehl Hillary L.
Published: November 2022

Aspergillus section Flavi species co-occur and contaminate crops, including maize and groundnuts, with aflatoxins. Competition among A. flavus genotypes is influenced by crop host, but competition between Aspergillus species has not been examined. The objectives of the current study were to (i) assess competition among four aflatoxin-producing species on maize and groundnuts and (ii) evaluate within-species variation in competitive ability during coinfection with another species on the two crops. For the first objective, maize and groundnut kernels were coinoculated with all possible pairs of A. flavus, A. parasiticus, A. aflatoxiformans, and an unnamed taxon known as the Lethal Aflatoxicosis Fungus (LAF). For the second objective, three isolates from each of the four species were coinoculated with a representative isolate of a competing species on the two hosts. In all experiments, isolates were cocultured for 7 days at 30°C, and then aflatoxins and total conidia were measured, and the percentages of each species within a treatment were assessed with quantitative pyrosequencing. Maize kernels supported greater aflatoxin production than groundnuts, whereas groundnuts supported greater sporulation than maize. Hosts differentially influenced competition between species, with A. flavus generally more competitive on maize and LAF more competitive on groundnuts. Overall, A. flavus and LAF were the most competitive species, whereas A. parasiticus was the least competitive. However, isolates within a species varied in competitive ability and in their response to host and competing species. Results suggest that although crop hosts influence Aspergillus community composition, within-species variability makes it difficult to predict outcomes of competition on a particular crop.

[Formula: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Spatially resolved transcriptomics: advances and applications
Authors: Duan Honglin , Cheng Tao , Cheng Hui
Published: November 2022

Spatial transcriptomics, which is capable of both measuring all gene activity in a tissue sample and mapping where this activity occurs, is vastly improving our understanding of biological processes and disease. The field has expanded rapidly in recent years, and the development of several new technologies has resulted in spatially resolved transcriptomics (SRT) becoming highly multiplexed, high-resolution, and high-throughput. Here, we summarize and compare the major methods of SRT, including imaging-based methods, sequencing-based methods, and in situ sequencing methods. We also highlight some typical applications of SRT in neuroscience, cancer biology, developmental biology, and hematology. Finally, we discuss future possibilities for improving spatially resolved transcriptomic methods and the expected applications of such methods, especially in the adult bone marrow, anticipating that new developments will unlock the full potential of spatially resolved multi-omics in both biological research and the clinic.
The Effect of Distant Reiki Sessions on Holistic Well-Being
Authors: Özcan Yüce Ulviye , Arpacı Afey , Kütmeç Yılmaz Cemile , Yurtsever Dilek , Üstün Gökçe Emine , Burkev Fatma Gönül , Yıldırım Gülcihan , Gökşin İlknur , Ünal Aslan Kevser Sevgi , Bektaş Akpınar Nilay , Altınbaş Akkaş Özlem , Yurtsever Sabire
Published: November 2022

This study investigated the effect of distant Reiki sessions on the holistic well-being of people without no acute/chronic diseases. The study was conducted between February 1 and March 31, 2022. The sample consisted of 180 healthy people living in a city in Turkey. Participants attended 20-minute distant Reiki sessions (intervention) for 4 consecutive days. Pretest data were collected using a personal information form, the Holistic Well-Being Scale (HWBS), the Positive and Negative Affect Schedule (PANAS), and the Subjective Vitality Scale (SVS). Posttest data were collected 2 days (posttest I) and 1 week after the intervention (posttest II) using the HWBS, PANAS, and SVS. There was a statistically significant difference between pretest and posttest I and II HWBS subscale scores (P < .05). There was a statistically significant difference between pretest and posttest PANAS and SVS scores (P < .05). Distant Reiki sessions improved participants' holistic well-being. They also helped them develop a positive mood, experience and perceive less sadness, and develop subjective vitality and cognitive awareness.
How the Shift Toward Working From Home Has Impacted People's Work and Private Life
Authors: Samuelsson Jonas , Johansson Gun , Forsell Yvonne , Möller Jette
Published: November 2022

Objective

In this study, we aimed to describe the effect of working from home on work conditions and private life by analyzing reported changes in different work-related factors.

Methods

We used descriptive analyses on cross-sectional data of 4985 people aged 20 to 67 years from Stockholm, Sweden collected in 2021. The prevalence of reported changes for factors related to work and private life was analyzed by degree of work from home and stratified by age, sex, and educational level.

Results

Participants who worked from home reported increased opportunities to structure the workday and combine work and private life, while at the same time experiencing increased isolation from the workplace. More females reported increased workload, whereas younger adults reported more changes overall.

Conclusions

Working from home was related to experiencing both positive and negative changes in work conditions and private life.
Attenuation by habitual alcohol drinking of the associations of obesity with blood pressure and pulse pressure
Authors: Wakabayashi Ichiro , Daimon Takashi
Published: November 2022

Background

Obesity and alcohol drinking are known to be risk factors for hypertension. However, it remains to be determined whether alcohol affects the relationships of obesity with blood pressure and pulse pressure.

Methods

The participants in this study were 29 171 men who had received annual health checkups. Relationships of BMI with blood pressure and pulse pressure were investigated in four subject groups divided by average daily alcohol consumption (grams of ethanol/day), non-, light (<22), moderate (≥22 and <44) and heavy (≥44) drinkers.

Results

BMI was significantly correlated with SBP and DBP levels both in nondrinkers and drinkers. The strength of the correlations was significantly weaker in drinkers than in nondrinkers. Odds ratios for hypertension in subjects with vs. subjects without obesity tended to be lower with an increase in alcohol intake (odds ratios with 95% confidence intervals: 4.09 (3.69–4.52) in nondrinkers; 3.11 (2.62–3.68) in light drinkers; 2.87 (2.61–3.16) in moderate drinkers; 2.81 (2.49–3.18) in heavy drinkers). Pulse pressure was weakly but significantly associated with BMI and obesity, and these associations were significantly weaker in heavy drinkers than in nondrinkers. There were significant odds ratios for hypertension and high pulse pressure of the interaction term between obesity and alcohol drinking.

Conclusion

The associations of BMI with blood pressure and pulse pressure and the associations of obesity with hypertension and high pulse pressure were weaker in drinkers than in nondrinkers. Thus, alcohol drinking attenuates the associations of obesity with hypertension and high pulse pressure.
Frequency of Medication Administration Timing Error in Hospitals
Authors: Pullam Trinity , Russell Cynthia L. , White-Lewis Sharon
Published: November 2022

Background:

Medication administration timing error (MATE) leads to poor medication efficacy, harm, and death. Frequency of MATE is understudied.

Purpose:

To determine MATE frequency, and characteristics and quality of reporting studies.

Methods:

A systematic review of articles between 1999 and 2021 was conducted using the Cumulative Index of Nursing and Allied Health Literature, ProQuest, and PubMed databases. Articles were scored for quality using the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) checklist.

Results:

Initially, 494 articles were screened; 23 were included in this review. MATE was defined as administration beyond 60 minutes before or after the scheduled time in 13 (57%) of the included studies. Measurement procedures included data abstraction, self-report, and observation. Frequency of MATE was 1% to 72.6%. Moderate study quality was found in 78% of articles.

Conclusion:

Research on MATE is characterized by inconsistent definitions, measurements procedures, and calculation techniques. High-quality studies are lacking. Many research improvement opportunities exist.
A scoping review on Para Judo
Authors: Gutiérrez-Santiago Alfonso , Gutiérrez-Santiago Jesús Antonio , Prieto-Lage Iván , Paramés-González Adrián , Suárez-Iglesias David , Ayán Carlos
Published: November 2022

This scoping review aimed to summarize the literature on Para judo comprehensively. A systematic search on WOS, PubMed, SPORTDiscus and Scopus was carried out up to July 2022, combining the keywords “judo” and “visual impairment”, “visual disability”, “visual deficiency”, “visually handicapped”, “low vision”, “sight loss”, “blind”, “disability” “deficiency” and “Paralympic”. The research question was focused on athletes with visual impairment (VI) who practiced judo at a competitive level. Five methodological phases were followed: (i) identifying the research question, (ii) identifying relevant studies, (iii) study selection, (iv) charting the data, and (v) collating, summarizing, and reporting the results. A total of 44 studies were analyzed. Three lines of research emerged: Physical Fitness (n = 18), Performance and/orSport Class (n = 15) and Physical and Mental Health (n = 11). Findings indicated that judokas with VI showed a similar fitness level to able-sighted judokas. Also, it was observed that Para judo shows a considerable injury incidence, which is not influenced by the degree of VI. The temporal structure of the combats, together with the studies focused on the optimal cut-off points between sports classes, confirmed the appropriateness of the recent changes in the regulations by which partially sighted judokas and functional blind judokas compete separately.
Outpatient mental health service use in major trauma survivors: A population-based cohort study from Ontario, Canada
Authors: Evans Christopher Charles Douglas , Li Wenbin , Jagelaviciute Gabriele , Morrison Ciara , Ng Rebecca , Brogly Susan B.
Published: November 2022

BACKGROUND

Mental health is recognized as an important outcome in major trauma survivors. There are limited data on how and when survivors access mental health services. Our objectives were to determine the frequency, timing, and factors associated with outpatient mental health service utilization in major trauma survivors.

METHODS

We conducted a population-based cohort study using linked administrative data on patients treated for major trauma in Ontario between 2009 and 2017. All trauma survivors were included in the cohort, and composite rates of outpatient mental health service use (family doctor, psychiatrist, or emergency department visits) were compared in the 3 years preinjury and postinjury. We used an exposure crossover study design and negative binomial regression with generalized estimating equations for the analysis. Multivariate logistic regression analyses were used to identify patient characteristics associated with mental health service use during the follow-up period.

RESULTS

There were 37,260 patients included in the cohort, predominantly men (70.8%) from urban areas (84.8%) suffering blunt trauma (89.7%). Among the patients, 47.4% used mental health services during the preinjury period and 61.8% during the postinjury period (absolute increase of 14.4%). Compared with the 3 years preinjury, the rate of mental health service use increased by 80% (rate ratio, 1.8; 95% confidence interval, 1.75–1.77) in the 3 years following injury. Most survivors (62.2%) used services within the first year following discharge. Postinjury mental health service use (adjusted odds ratio, 3.4; 95% confidence interval, 2.2–3.7) was most strongly associated with preinjury mental health service use.

CONCLUSION

Preinjury and postinjury outpatient mental health service use is common in trauma patients, with preinjury service use predictive of ongoing service use. Mental health concerns should be an expected outcome of major trauma and efforts made to implement and expand access to services for injury survivors across trauma systems.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level IV.
Bacterial community dynamics and associated genes in hydrocarbon contaminated soil during bioremediation using brewery spent grain
Authors: Nnadi Mabel Owupele , Bingle Lewis , Thomas Keith
Published: November 2022

Brewery spent grain (BSG) has previously been exploited in bioremediation. However, detailed knowledge of the associated bacterial community dynamics and changes in relevant metabolites and genes over time, is limited. This study investigated the bioremediation of diesel contaminated soil amended with BSG. We observed the complete degradation of three Total Petroleum Hydrocarbon (TPH C10 – C28) fractions in amended treatments as compared to one fraction in the unamended treatments. The biodegradation rate constant was higher in amended treatments (0.1021 k) than in unamended (0.059 k) and bacterial CFUs increased significantly in amended treatments. The degradation compounds observed fitted into the elucidated diesel degradation pathways and quantitative PCR results showed that the gene copy numbers of all three associated degradation genes, alkB , catA and xylE, were significantly higher in amended treatments. High-throughput sequencing of 16S rRNA gene amplicons showed that amendment with BSG enriched autochthonous hydrocarbon degraders. Also, community shifts of the genera Acinetobacter and Pseudomonas correlated with the abundance of catabolic genes and degradation compounds observed. This study showed that these two genera are present in BSG and thus, may be associated with the enhanced biodegradation observed in amended treatments. The results suggest that the combined evaluation of TPH, microbiological, metabolite and genetic analysis provides a useful wholistic approach to assessing bioremediation.
Efficient risk mitigation planning for a clinical trial
Authors: Shnaydman Vladimir
Published: November 2022

Each clinical trial faces numerous risks. Neglecting or reacting spontaneously at each materialized risk may delay trial completion, affect trial objectives and even derail the clinical trial. At the same time, pre-allocating excessive contingency resources to eliminate all potential risks, even with a low probability of occurrence and impact, may not be necessary. Therefore, optimal risk planning means finding the “right” balance between contingency resources, risk mitigation strategy, and risk tolerance.

Most risk planning publications focus only on risk identification and risk assessment. Risk mitigation strategy planning is often overlooked. A contingency budget is routinely assigned as a percentage of a clinical trial budget, e.g., 10-20%, and is not aligned with the clinical trial risk level. Therefore, to derive an effective clinical trial risk mitigation strategy, a new methodology based on mathematical modeling was developed and validated for a Ph2 clinical trial.
Bayesian network enables interpretable and state-of-the-art prediction of immunotherapy responses in cancer patients
Authors: Hozumi Hideki , Shimizu Hideyuki
Published: November 2022

Immune checkpoint inhibitors, especially PD-1/PD-L1 blockade, have revolutionized cancer treatment and brought tremendous benefits to patients who otherwise would have had a limited prognosis. Nonetheless, only a small fraction of patients responds to immunotherapy, and the costs and side effects of immune checkpoint inhibitors cannot be ignored. With the advent of machine and deep learning, clinical and genetic data has been used to stratify patient responses to immunotherapy. Unfortunately, these approaches have typically been “black-box” methods that are unable to explain their predictions, thereby hindering their clinical and responsible application. Herein, we developed a “white-box” Bayesian network model that achieves accurate and interpretable predictions of immunotherapy responses against non-small cell lung cancer (NSCLC). This Tree-Augmented naïve Bayes model (TAN) precisely predicted durable clinical benefits and distinguished two clinically significant subgroups with distinct prognoses. Furthermore, Our state-of-the-art white-box TAN approach achieved greater accuracy than previous methods. We hope our model will guide clinicians in selecting NSCLC patients who truly require immunotherapy and expect our approach will be easily applied to other types of cancer.

Structured Abstract

Background

Immune checkpoint inhibitors have revolutionized cancer treatment. Given that only a small fraction of patients responds to immunotherapy, patient stratification is a pressing concern. Unfortunately, the “black-box” nature of most of the proposed stratification methods, and their far from satisfactory accuracy, has hindered their clinical application.

Method

We developed a “white-box” Bayesian network model, with interpretable architecture, that can accurately predict immunotherapy response against non-small cell lung cancer (NSCLC). We collected clinical and genetic information from several independent studies, and integrated this via the Tree-Augmented naïve Bayes (TAN) approach.

Findings

This TAN model precisely predicted durable clinical benefit and distinguished two clinically significant subgroups with distinct prognoses, achieving state-of-the-art performance than previous methods. We also verified that TAN succeeded in detecting meaningful interactions between variables from data-driven approach. Moreover, even when data have missing values, TAN successfully predicted their prognosis.

Interpretation

Our model will guide clinicians in selecting NSCLC patients who genuinely require immunotherapy. We expect this approach to be easily applied to other types of cancer. To accelerate the uptake of personalized medicine via access to accurate and interpretable models, we provide a web application (https://pred-nsclc-ici-bayesian.shinyapps.io/Bayesian-NSCLC/) for use by the researchers and clinicians community.

Funding

KAKENHI grant from the Japan Society for the Promotion of Science (JSPS) to H.S (21K17856).