bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and validation of models for two‐week mortality of inpatients with COVID‐19 infection: A large prospective cohort study
Authors: Fathi Mohammad , Markazi Moghaddam Nader , Kheyrati Leila
Published: January 2022

Recognizing COVID‐19 patients at a greater risk of mortality assists medical staff to identify who benefits from more serious care. We developed and validated prediction models for two‐week mortality of inpatients with COVID‐19 infection based on clinical predictors. A prospective cohort study was started in February 2020 and is still continuing. In total, 57,705 inpatients with both a positive reverse transcription‐polymerase chain reaction test and positive chest CT findings for COVID‐19 were included. The outcome was mortality within 2 weeks of admission. Three prognostic models were developed for young, adult, and senior patients. Data from the capital province (Tehran) of Iran were used for validation, and data from all other provinces were used for development of the models. The model Young, was well‐fitted to the data (p < 0.001, Nagelkerke R2 = 0.697, C‐statistics = 0.88) and the models Adult (p < 0.001, Nagelkerke R2 = 0.340, C‐statistics = 0.70) and Senior (p < 0.001, Nagelkerke R2 = 0.208, C‐statistics = 0.68) were also significant. Intubation, saturated O2 < 93%, impaired consciousness, acute respiratory distress syndrome, and cancer treatment were major risk factors. Elderly people were at greater risk of mortality. Young patients with a history of blood hypertension, vomiting, and fever; and adults with diabetes mellitus and cardiovascular disease had more mortality risk. Young people with myalgia; and adult patients with nausea, anorexia, and headache showed less risk of mortality than others.
Fetal neurosonography at 31–35 weeks reveals altered cortical development in pre‐eclampsia with and without small‐for‐gestational‐age fetus
Authors: Basso A. , Youssef L. , Nakaki A. , Paules C. , Miranda J. , Casu G. , Salazar L. , Gratacos E. , Eixarch E. , Crispi F. , Crovetto F.
Published: January 2022

Objective

To explore the pattern of fetal cortical development in pregnancies complicated by pre‐eclampsia (PE), with and without a small‐for‐gestational‐age (SGA) fetus, compared to uncomplicated pregnancies.

Methods

This was a prospective observational study including singleton pregnancies complicated by normotensive SGA (birth weight < 10th centile) (n = 77), PE with an appropriate‐for‐gestational‐age (AGA) fetus (n = 76) or PE with a SGA fetus (n = 67), and 128 uncomplicated pregnancies (normotensive AGA) matched by gestational age at ultrasound. All pregnancies underwent detailed neurosonography, using a transabdominal and transvaginal approach, at 31–35 weeks' gestation to assess the depth of the insula, Sylvian fissure, parieto‐occipital sulcus, cingulate sulcus and calcarine sulcus. All measurements were adjusted for biparietal diameter (BPD). In addition, a grading score of cortical development was assigned to each brain structure, ranging from Grade 0 (no development) to Grade 5 (maximum development). Univariate and multiple regression analyses were conducted.

Results

Similar to findings in previous studies, normotensive pregnancies with a SGA fetus showed significant differences in cortical development compared with controls, with reduced Sylvian fissure depth adjusted for BPD (14.5 ± 2.4 vs 16.6 ± 2.3; P < 0.001) and increased insula depth adjusted for BPD (33.2 ± 2.0 vs 31.8 ± 2.0; P < 0.001). Interestingly, a similar cortical development pattern was observed in PE pregnancies with a SGA fetus and in PE pregnancies with an AGA fetus, manifested by reduced Sylvian fissure depth adjusted for BPD (14.2 ± 2.3 and 14.3 ± 2.3 vs 16.6 ± 2.3; P < 0.001 for both) and greater insula depth adjusted for BPD (33.2 ± 2.1 and 32.8 ± 1.7 vs 31.8 ± 2.0; P < 0.001 for both) compared with controls. No significant differences were observed in parieto‐occipital, cingulate sulcus or calcarine sulcus depth across the study groups. The Sylvian fissure was scored as Grade 4 in significantly more (93.2% vs 59.5%) and as Grade 5 in significantly fewer (2.7% vs 37.3%) PE pregnancies with an AGA fetus compared with controls (P < 0.05 for both). These differences remained significant even after statistical adjustment for potential confounders, including ethnicity, low socioeconomic status, nulliparity, chronic hypertension, pregestational diabetes, assisted reproductive technologies, smoking and fetal gender, with the application of Benjamini–Hochberg procedure for multiple comparisons.

Conclusions

PE with or without SGA is associated with a differential fetal cortical development pattern which is similar to that described previously in small fetuses. Future research is warranted to elucidate better the mechanism(s) underlying these changes. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.
Combinational application of metal–organic frameworks‐based nanozyme and nucleic acid delivery in cancer therapy
Authors: Ni Dongqi , Lin Jinhui , Zhang Nuozi , Li Shilin , Xue Yueguang , Wang Ziyao , Liu Qianglin , Liu Kai , Zhang Hongjie , Zhao Yuliang , Chen Chunying , Liu Ying
Published: January 2022

The rapid development of nanotechnology has generated numerous ideas for cancer treatment, and a wide variety of relevant nanoparticle platforms have been reported. Metal–organic frameworks (MOFs) have been widely investigated as an anti‐cancer drug delivery vehicle owing to their unique porous hybrid structure, biocompatibility, structural tunability, and multi‐functionality. MOF materials with catalytic activity, known as nanozymes, have applications in photodynamic and chemodynamic therapy. Nucleic acids have also attracted increasing research attention owing to their programmability, ease of synthesis, and versatility. A variety of functional DNAs and RNAs have been applied both therapeutically (gene‐targeting drugs for cancer treatment) and nontherapeutically (used as modified materials to enhance the therapeutic effects of other nanomedicines). The combined use of MOFs and functional nucleic acids have been extensively investigated and has been associated with excellent tumor‐suppressor activity in various treatment methods. In this review, we summarize the progress in the research and development of tumor therapy based on MOFs and nucleic acid delivery over recent years, focusing on the combinational use of different delivery and design strategies for MOF/therapeutic nucleic acid platforms. We further summarize the strategies for combining MOFs (universal carrier, functional carrier) and nucleic acids (therapeutic nucleic acids, nontherapeutic nucleic acids) and discuss the corresponding therapeutic effects in cancer treatment.

This article is categorized under:

Nanotechnology Approaches to Biology > Nanoscale Systems in Biology

Therapeutic Approaches and Drug Discovery > Emerging Technologies
Klerman's “credo” reconsidered:neo‐Kraepelinianism, Spitzer's views, and what we can learn from the past
Authors: Wakefield Jerome C.
Published: January 2022

In 1978, G. Klerman published an essay in which he named the then‐nascent “neo‐Kraepelinian” movement and formulated a “credo” of nine propositions expressing the movement's essential claims and aspirations. Klerman's essay appeared on the eve of the triumph of neo‐Kraepelinian ideas in the DSM‐III. However, this diagnostic system has subsequently come under attack, opening the way for competing proposals for the future of psychiatric nosology. To better understand what is at stake, in this paper I provide a close reading and consideration of Klerman's credo in light of the past forty years of research and reflection. The credo is placed in the context of two equally seminal publications in the same year, one by S. Guze, the leading neo‐Kraepelinian theorist, and the other by R. Spitzer and J. Endicott, defining mental disorder. The divergences between Spitzer and standard neo‐Kraepelinianism are highlighted and argued to be much more important than is generally realized. The analysis of Klerman's credo is also argued to have implications for how to satisfactorily resolve the current nosological ferment in psychiatry. In addition to issues such as creating descriptive syndromal diagnostic criteria, overthrowing psychoanalytic dominance of psychiatry, and making psychiatry more scientific, neo‐Kraepelinians were deeply concerned with the conceptual issue of the nature of mental disorder and the defense of psychiatry's medical legitimacy in response to antipsychiatric criticisms. These issues cannot be ignored, and I argue that proposals currently on offer to replace the neo‐Kraepelinian system, especially popular proposals to replace it with dimensional measures, fail to adequately address them.
The influence of welfare and bonds with animals on the job satisfaction of felid keepers in North America
Authors: DeSmet Annabel , Ogle Brian
Published: January 2022

The current study set out to examine the perceptions of felid welfare in zoos and elucidate the factors that influence an individual animal care professional's acceptance and recognition of welfare. A total of 121 felid keepers employed in an Association of Zoos & Aquariums facility were included in analysis. Results demonstrate job satisfaction is directly linked to access to training on welfare topics. The relationship between job satisfaction and the fulfillment of the Five Freedoms is positively correlated. Additionally, overall job satisfaction does not appear to influence the bond with felids, but it does with other zoo animals. Those with lower reported job satisfaction demonstrate an overall lower bond with nonfelids, where this not observed in felids. Participants in this study demonstrate the direct connection between job satisfaction and perceived fulfillment of the Five Freedoms. Participants who were provided access to training and information on animal welfare often demonstrated a higher job satisfaction, more positive perception of their employer, and overall view of zoos meeting the Five Freedoms with captive felids.
The “Sustainability Doctrine” in Donor-Driven Maternal Health Programs in Tanzania
Authors: Marten Meredith G.
Published: January 2022

Strengthening health systems to provide equitable, sustainable health care has been identified as essential for improving maternal and reproductive health. Many donors and non-governmental organizations (NGOs) have contributed to undermining health system strengthening, however, through adhering to what Swidler and Watkins call the “sustainability doctrine,” policies that prioritize time-limited, targeted interventions best suited for short-term funding streams, rather than the long-term needs of local populations. This chapter presents ethnographic data from semi-structured and key informant interviews with 16 policymakers and NGO directors in Dar es Salaam, Tanzania from 2011 to 2012. I illustrate how sustainability doctrine policies were put into practice, and how they have persisted, despite their shortcomings, using examples of donor-prioritized maternal healthcare initiatives in Tanzania rolled-out several years apart: prevention of mother-to-child transmission of HIV (PMTCT) and basic emergency obstetric and newborn care (BEmONC) programs in the late 2000s, and more recent efforts to implement respectful maternity care (RMC) programs. I focus on several issues informants identified as crippling efforts to build strong health systems, particularly the internal brain drain of healthcare workers from the public sector to higher-paying NGO jobs, and the prioritization of types of programs donors believed could be sustained after the funding period ended, specifically trainings and workshops. I describe how despite these issues, international organizations still design and implement less effective programs that often fail to account for local circumstances in their efforts to solve some of the more intractable health issues facing Tanzania today, in particular, the country’s stagnating maternal mortality rate. In this chapter, I argue that practices promoted and implemented under the guise of “sustainability” in policy papers and reports generated by donors paradoxically contribute to health system precarity in Tanzania.
Note on the asymptotic structure of Kerr-Schild form
Authors: Mao Pujian , Zhao Weicheng
Published: January 2022

Abstract

The Kerr-Schild form provides a natural way of realizing the classical double copy that relates exact solutions in general relativity to exact solutions in gauge theory. In this paper, we examine the asymptotic structure of Kerr-Schild form. In Newman-Unti gauge, we find a generic solution space satisfying the Kerr-Schild form in series expansion around null infinity. The news function in the solution space is chiral and can not lead to a mass loss formula. A class of asymptotically flat complex pp-wave solutions in closed form is obtained from the solution space.
Hepatitis-B-Impfstoffe – Geschichte, Erfolge, Herausforderungen und Perspektiven
Authors: Gerlich Wolfram H.
Published: January 2022

Die ersten Impfversuche gegen das Hepatitis-B-Virus (HBV) erfolgten 1970, noch bevor die Natur des dafür verwendeten „Australia-Antigens“ bekannt war. Bald darauf wurde dieses Antigen als Hüllprotein des HBV erkannt (HBV Surface Antigen, HBsAg), dann aus HBV-haltigem Plasma gereinigt und später gentechnisch in Hefezellen hergestellt. Die hohe Wirksamkeit des HBsAg-Impfstoffs wurde vielfach bewiesen, insbesondere bei Neugeborenen von HBV-infizierten Müttern, die sonst fast immer chronische HBV-Träger werden. Auch bei älteren Kindern und Erwachsenen schützt die Impfung und wird seit 1984 weltweit angewendet, was zu einer ungefähr 10-fachen Abnahme der HBV-Infektionen bei den Geimpften geführt hat.

Es gibt dennoch verschiedene Herausforderungen bei der Hepatitis-B-Impfung. Bei Neugeborenen von hochvirämischen Müttern kann die Impfung versagen. Bei verringerter Immunkompetenz kann die Bildung schützender Antikörper ausbleiben, aber auch bei Risikofaktoren wie höherem Alter, Rauchen oder Übergewicht. Frühe Impfstudien belegten, dass Impfstoffe mit dem HBsAg-Subtyp adw2 auch gegen HBV mit anderen HBsAg-Subtypen schützen, neuere Beobachtungen zeigen aber, dass die Schutzwirkung gegen heterologe Subtypen schwächer ist. Gelegentlich werden auch Escape-Mutationen beobachtet.

Die meisten jetzigen Impfstoffe beruhen auf dem Kenntnisstand vor 40 Jahren und könnten wesentlich verbessert werden. Eine Einbeziehung der bislang fehlenden PräS-Domänen der HBV-Hülle in die Impfstoffe würde die wichtigsten schützenden T‑ und B‑Zellepitope einbringen. Die Expression in Säugerzellkulturen verbessert die native Faltung der neutralisierenden HBsAg-Epitope und die Verwendung von regional vorherrschenden HBsAg-Subtypen würde die Schutzwirkung erhöhen. Optimale Adjuvanzien oder Epitopträger könnten die Immunogenität auch für eine HBV-Immuntherapie steigern.
Frequent FGFR1 hotspot alterations in driver-unknown low-grade glioma and mixed neuronal-glial tumors
Authors: Engelhardt Sophie , Behling Felix , Beschorner Rudi , Eckert Franziska , Kohlhof Patricia , Tatagiba Marcos , Tabatabai Ghazaleh , Schuhmann Martin U. , Ebinger Martin , Schittenhelm Jens
Published: January 2022

Purpose

Low-grade gliomas (LGG) and mixed neuronal-glial tumors (MNGT) show frequent MAPK pathway alterations. Oncogenic fibroblast growth factor receptor 1 (FGFR1) tyrosinase kinase domain has been reported in brain tumors of various histologies. We sought to determine the frequency of FGFR1 hotspot mutations N546 and K656 in driver-unknown LGG/MNGT and examined FGFR1 immunohistochemistry as a potential tool to detect those alterations.

Methods

We analyzed 476 LGG/MNGT tumors for KIAA-1549-BRAF fusion, IDH1/2, TERT promotor, NF1, H3F3A and the remaining cases for FGFR1 mutation frequency and correlated FGFR1 immunohistochemistry in 106 cases.

Results

368 of 476 LGG/MNGT tumors contained non-FGFR1 alterations. We identified 9 FGFR1 p.N546K and 4 FGFR1 p.K656E mutations among the 108 remaining driver-unknown samples. Five tumors were classified as dysembryoplastic neuroepithelial tumor (DNT), 4 as pilocytic astrocytoma (PA) and 3 as rosette-forming glioneuronal tumor (RGNT). FGFR1 mutations were associated with oligodendroglia-like cells, but not with age or tumor location. FGFR1 immunohistochemical expression was observed in 92 cases. FGFR1 immunoreactivity score was higher in PA and DNT compared to diffuse astrocytoma, but no correlation between FGFR1 mutation in tumors and FGFR1 expression level was observed.

Conclusion

FGFR1 hotspot mutations are the fifth most prevailing alteration in LGG/MNGT. Performing FGFR1 sequencing analysis in driver-unknown low-grade brain tumors could yield up to 12% FGFR1 N546/K656 mutant cases.
Reliability of televisits for patients with mild relapsing–remitting multiple sclerosis in the COVID-19 era
Authors: Toscano Simona , Patti Francesco , Chisari Clara Grazia , Arena Sebastiano , Finocchiaro Chiara , Schillaci Carmela Elita , Zappia Mario
Published: January 2022

Background

Evidence of the cost-effectiveness of telemedicine (TM) for the management of Multiple Sclerosis (MS) has been provided recently. However, some doubts persist about the accuracy of neurological examinations performed remotely.

Objectives

This study investigated the reliability of neurological evaluations performed through TM in mild MS patients as compared with standard in-person visits.

Methods

In total, 76 patients with relapsing–remitting MS and Expanded Disability Status Scale (EDSS) ≤ 3.5 were consecutively recruited. Of them, 40 patients (52.6%) accepted to undergo both in-person and TM evaluations with independent examiners within 48 h. We alternatively asked patients to assure or not the presence of a caregiver during TM visits. A satisfaction questionnaire was administered to all participants.

Results

The inter-rater agreement attributed by two independent neurologists during TM visit was high (κ > 0.80) for EDSS and Functional Systems (FS) scores. Moderate agreement between TM and in-person evaluations emerged for pyramidal (κ = 0.57; p < 0.001), brainstem (κ = 0.57; p < 0.001), bowel and bladder (κ = 0.54; p < 0.001) and sensory (κ = 0.51; p < 0.001) FS scores, higher in patients providing the support of a caregiver. A good reliability was reported for EDSS scores computed during remote and in-person visits (ICC = 0.83; 95% CI 0.70–0.91; p < 0.001).

Conclusions

Despite the complexity of neurological examination, TM could be useful in monitoring MS patients with low disability.
Gay Dating App Users Support and Utilize Sexual Health Features on Apps
Authors: Hecht Jennifer , Zlotorzynska Maria , Sanchez Travis H. , Wohlfeiler Dan
Published: January 2022

Men who have sex with men (MSM) frequently meet sex partners through dating apps. Research has demonstrated an association between app use and greater number of sex partners and STIs, but dating apps also pose an opportunity for intervention. By advocating for sexual health features on dating apps, Building Healthy Online Communities (BHOC) aims to increase communication about sexual health among app users. In partnership with Emory University, BHOC added questions to an annual survey of MSM. The questions assessed awareness and uptake of profile fields and sexual health features on the dating apps. Among survey participants, 67% (6737/10,129) reported using dating apps to meet a partner in the past year. Among this group, 77% (4993/6525) reported awareness of sexual health features. 61% of app users (2866/4721) who were aware of them reported using one or more sexual health features. BHOC continues to advocate for increased uptake of these features.
Multi-taxa spatial conservation planning reveals similar priorities between taxa and improved protected area representation with climate change
Authors: Critchlow Rob , Cunningham Charles A. , Crick Humphrey Q. P. , Macgregor Nicholas A. , Morecroft Michael D. , Pearce-Higgins James W. , Oliver Tom H. , Carroll Matthew J. , Beale Colin M.
Published: January 2022

Protected area (PA) networks have in the past been constructed to include all major habitats, but have often been developed through consideration of only a few indicator taxa or across restricted areas, and rarely account for global climate change. Systematic conservation planning (SCP) aims to improve the efficiency of biodiversity conservation, particularly when addressing internationally agreed protection targets. We apply SCP in Great Britain (GB) using the widest taxonomic coverage to date (4,447 species), compare spatial prioritisation results across 18 taxa and use projected future (2080) distributions to assess the potential impact of climate change on PA network effectiveness. Priority conservation areas were similar among multiple taxa, despite considerable differences in spatial species richness patterns; thus systematic prioritisations based on indicator taxa for which data are widely available are still useful for conservation planning. We found that increasing the number of protected hectads by 2% (to reach the 2020 17% Aichi target) could have a disproportionate positive effect on species protected, with an increase of up to 17% for some taxa. The PA network in GB currently under-represents priority species but, if the potential future distributions under climate change are realised, the proportion of species distributions protected by the current PA network may increase, because many PAs are in northern and higher altitude areas. Optimal locations for new PAs are particularly concentrated in southern and upland areas of GB. This application of SCP shows how a small addition to an existing PA network could have disproportionate benefits for species conservation.
Immunotherapy toxicity: identification and management
Authors: Gumusay O. , Callan J. , Rugo H. S.
Published: January 2022

The widespread adoption of immunotherapy has revolutionized the treatment of various cancer types, including metastatic triple-negative breast cancer (TNBC), which has long been associated with poor prognostic outcomes. In particular, immune checkpoint inhibitors (ICIs) that target and inhibit programmed cell death-1 (PD-1) and programmed cell death ligand-1 (PD-L1), have shown promising results in the treatment of patients with metastatic TNBC. However, while manipulating the immune system to induce antitumor response, ICIs can also lead to a unique set of immune-related adverse events (IRAEs), which differ from standard chemotherapy toxicities due to their immune-based origin. These toxicities require highly specific management, including guidance from multidisciplinary specialists. The primary treatment strategy against IRAEs is systemic corticosteroid use, but additional treatment approaches may also involve supportive care, additional immunosuppression, and concurrent treatment delay or discontinuation. Given the rising prevalence of ICI therapy, it is essential to educate clinicians on the presentation and management of these potentially life-threatening events so that they are identified early and treated appropriately. Using data from recent clinical trials, this review will focus on known IRAEs, particularly those seen in patients with breast cancer, and will summarize their prevalence, severity, and outcomes. We will discuss optimal strategies for early recognition and management, as well as approaches toward cautious retreatment following resolution of IRAEs.
Cost-Effectiveness of Lipid-Lowering Therapies for Cardiovascular Prevention in Germany
Authors: Michaeli Daniel Tobias , Michaeli Julia Caroline , Boch Tobias , Michaeli Thomas
Published: January 2022

Purpose

Novel pharmaceutical treatments reducing cardiovascular events in dyslipidaemia patients must demonstrate clinical efficacy and cost-effectiveness to promote long-term adoption by patients, physicians, and insurers.

Objective

To assess the cost-effectiveness of statin monotherapy compared to additive lipid-lowering therapies for primary and secondary cardiovascular prevention from the perspective of Germany’s healthcare system.

Methods

Transition probabilities and hazard ratios were derived from cardiovascular outcome trials for statin combinations with icosapent ethyl (REDUCE-IT), evolocumab (FOURIER), alirocumab (ODYSSEY), ezetimibe (IMPROVE-IT), and fibrate (ACCORD). Costs and utilities were retrieved from previous literature. The incidence of major adverse cardiovascular events was simulated with a Markov cohort model. The main outcomes were the incremental cost-effectiveness ratios (ICER) per quality adjusted life year (QALY) gained.

Results

For primary prevention, the addition of icosapent ethyl to statin generated 0.81 QALY and €14,732 costs (ICER: 18,133), whereas fibrates yielded 0.63 QALY and € − 10,516 costs (ICER: − 16,632). For secondary prevention, the addition of ezetimibe to statin provided 0.61 QALY at savings of € − 5,796 (ICER: − 9,555) and icosapent ethyl yielded 0.99 QALY and €14,333 costs (ICER: 14,485). PCSK9 inhibitors offered 0.55 and 0.87 QALY at costs of €62,722 and €87,002 for evolocumab (ICER: 114,639) and alirocumab (ICER: 100,532), respectively. A 95% probability of cost-effectiveness was surpassed at €20,000 for icosapent ethyl (primary and secondary prevention), €119,000 for alirocumab, and €149,000 for evolocumab.

Conclusions

For primary cardiovascular prevention, a combination therapy of icosapent ethyl plus statin is a cost-effective use of resources compared to statin monotherapy. For secondary prevention, icosapent ethyl, ezetimibe, evolocumab, and alirocumab increase patient benefit at different economic costs.
SARS-CoV-2 Spike protein is not pro-inflammatory in human primary macrophages: endotoxin contamination and lack of protein glycosylation as possible confounders
Authors: Cinquegrani Gloria , Spigoni Valentina , Iannozzi Nicolas Thomas , Parello Vanessa , Bonadonna Riccardo C. , Dei Cas Alessandra
Published: January 2022

Introduction

The inflammatory potential of SARS-CoV-2 Spike S1 (Spike) has never been tested in human primary macrophages (MΦ). Different recombinant Spikes might display different effects in vitro, according to protein length and glycosylation, and endotoxin (lipopolysaccharide, LPS) contamination.

Objectives

To assess (1) the effects of different Spikes on human primary MΦ inflammation; (2) whether LPS contamination of recombinant Spike is (con)cause in vitro of increased MΦ inflammation.

Methods

Human primary MΦ were incubated in the presence/absence of several different Spikes (10 nM) or graded concentrations of LPS. Pro-inflammatory marker expression (qPCR and ELISA) and supernatant endotoxin contamination (LAL test) were the main readouts.

Results

LPS-free, glycosylated Spike (the form expressed in infected humans) caused no inflammation in human primary MΦ. Two (out of five) Spikes were contaminated with endotoxins ≥ 3 EU/ml and triggered inflammation. A non-contaminated non-glycosylated Spike produced in E. coli induced MΦ inflammation.

Conclusions

Glycosylated Spike per se is not pro-inflammatory for human MΦ, a feature which may be crucial to evade the host innate immunity. In vitro studies with commercially available Spike should be conducted with excruciating attention to potential LPS contamination.

Graphical abstract
Incorporating external trial data to improve survival extrapolations: a pilot study of the COU-AA-301 trial
Authors: Bullement Ash , Kearns Benjamin
Published: January 2022

Survival extrapolation plays a key role within cost effectiveness analysis and is often subject to substantial uncertainty. Use of external data to improve extrapolations has been identified as a key research priority. We present findings from a pilot study using data from the COU-AA-301 trial of abiraterone acetate for metastatic castration-resistant prostate cancer, to explore how external trial data may be incorporated into survival extrapolations. External trial data were identified via a targeted search of technology assessment reports. Four methods using external data were compared to simple parametric models (SPMs): informal reference to external data to select appropriate SPMs, piecewise models with, and without, hazard ratio adjustment, and Bayesian models fitted with a prior on the shape parameter(s). Survival and hazard plots were compared, and summary metrics (point estimate accuracy and restricted mean survival time) were calculated. Without consideration of external data, several SPMs may have been selected as the ‘best-fitting’ model. The range of survival probability estimates was generally reduced when external data were included in model estimation, and external hazard plots aided model selection. Different methods yielded varied results, even with the same data source, highlighting potential issues when integrating external trial data within model estimation. By using external trial data, the most (in)appropriate models may be more easily identified. However, benefits of using external data are contingent upon their applicability to the research question, and the choice of method can have a large impact on extrapolations.
Characterizing Daily-Life Social Interactions in Adolescents and Young Adults with Neurodevelopmental Disorders: A Comparison Between Individuals with Autism Spectrum Disorders and 22q11.2 Deletion Syndrome
Authors: Feller Clémence , Ilen Laura , Eliez Stephan , Schneider Maude
Published: January 2022

Social impairments are common features of 22q11.2 deletion syndrome (22q11DS) and autism spectrum disorders (ASD). The Ecological Momentary Assessment (EMA) allowed access to daily-life information in order to explore the phenomenology of social interactions. 32 individuals with 22q11DS, 26 individuals with ASD and 44 typically developing peers (TD) aged 12–30 were assessed during 6 days 8 times a day using a mobile app. Participants with 22q11DS and ASD did not spend more time alone but showed distinct implication in the social sphere than TD. Distinct profiles emerged between the two conditions regarding the subjective experience of aloneness and the subjective experience of social interactions. This study highlights distinct social functioning profiles in daily-life in 22q11DS and ASD that points towards different therapeutic targets.
An Islamic Form of Logotherapy in the Treatment of Depression, Anxiety and Stress Symptoms in University Students in Iran
Authors: Fereydouni Shapour , Forstmeier Simon
Published: January 2022

Previous research demonstrated that spiritually sensitive psychotherapy is an effective treatment for clients with depression or anxiety, with outcomes equivalent to secular control interventions. The goal of this study was to evaluate the efficacy of spiritually sensitive logotherapy intervention in the treatment of depression, anxiety, and stress symptoms in university students in Iran. Sixty students with elevated depression symptoms (Beck Depression Inventory II, BDI-II, 22 or greater) were randomly assigned to either a twelve-session group logotherapy programme or a control group. Results showed that spiritually sensitive logotherapy significantly reduced depression, anxiety, and stress, and significantly more so than in the control group (e.g. interaction effect for BDI-II:F = 56.8,p < 0.001, with a large effect size).
A New Filter Based Cultivation Approach for Improving Aspergillus Identification using Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS)
Authors: Salah Husam , Kolecka Anna , Rozaliyani Anna , Wahyuningsih Retno , Taj-Aldeen Saad J. , Boekhout Teun , Houbraken Jos
Published: January 2022

Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS) is widely used in clinical laboratories for routine identification of bacteria and yeasts. However, methodological difficulties are still apparent when applied to filamentous fungi. The liquid cultivation method recommended by Bruker Daltonics GmbH for identification of filamentous fungi by MALDI-TOF MS is labour intensive and time-consuming. In this study, growth of Aspergillus species on different (porous) surfaces was investigated with the aim to develop a more reliable, quicker and less laborious identification method using MALDI-TOF MS. Mycelial growth without sporulation mimicking liquid cultivation and reliable MALDI-TOF MS spectra were obtained when A. fumigatus strains were grown on and in between a polycarbonate membrane filter on Sabouraud dextrose agar. A database of in-house reference spectra was created by growing Aspergillus reference strains (mainly focusing on sections Fumigati and Flavi) under these selected conditions. A test set of 50 molecularly identified strains grown under different conditions was used to select the best growth condition for identification and to perform an initial validation of the in-house database. Based on these results, the cultivation method on top of a polycarbonate filter proved to be most successful for species identification. This method was therefore selected for the identification of two sets of clinical isolates that mainly consisted of Aspergilli (100 strains originating from Indonesia, 70 isolates from Qatar). The results showed that this cultivation method is reliable for identification of clinically relevant Aspergillus species, with 67% and 76% correct identification of strains from Indonesia and Qatar, respectively. In conclusion, cultivation of Aspergilli on top of a polycarbonate filter showed improved results compared to the liquid cultivation protocol recommended by Bruker in terms of percentage of correct identification, ease of MSP creation, time consumption, cost and labour intensity. This method can be reliably applied for identification of clinically important Aspergilli and has potential for identification of other filamentous fungi.
Online interventions to help college students to improve the degree of integration of their argumentative synthesis
Authors: Luna María , Villalón Ruth , Martínez-Álvarez Isabel , Mateos Mar
Published: January 2022

Writing an argumentative synthesis is a common but demanding task, consequently undergraduates require some instruction. The objective of this study was to test the effectiveness of two interventions on integrative argumentation: one of them was focused on the product features of argumentative texts; and the other one on the processes involved in the written argumentation. Sixty-six undergraduate students participated voluntarily. As an academic task, they were asked to write a pre-test synthesis after reading two sources which presented contradictory positions about an educational issue, then to read two new texts about a different but equivalent issue, and write a post-test synthesis following one of two types of instructional virtual environments. The instructions, implemented in Moodle, presented similar tools, employing videos, graphic organizers, and exercises. The first condition (n = 33) focused on the linguistic features while the second (n = 33), focused on the process, including explicit instruction and a script with critical questions to guide the reading and writing processes. In this study we have also analyzed how the students in the process condition answered some of the critical questions. The results show that the level of integration of the written products improved in both conditions, although this improvement was more pronounced in the process intervention. Nonetheless, the products that achieved medium and maximum integration were still limited. Despite the lack of a relationship between how students answered the critical questions and the level of integration in their post-test, the case analysis highlights certain educational implications and further research.
Meaning Making with Multiple Representations: a Case Study of a Preservice Teacher Creating a Digital Explanation
Authors: Nielsen Wendy , Turney Annette , Georgiou Helen , Jones Pauline
Published: January 2022

The construction of dynamic multimedia products requires the selection and integration of a range of semiotic resources. As an assessment task for preservice teachers, this construction process is complex but has significant potential for learning. To investigate how weaving together multiple representations in such tasks enables learners to develop conceptual understanding, the paper presents an indicative case study of a 2nd-year preservice primary (K-6) teacher who created a digital explanation on the topic of ‘transparency’ for stage 3 children (ages 11–12). We focus on data gathered during the 3-h construction process including artefacts such as images, online searches, websites accessed and paper records used for planning; the digital explanation as product; audio and video capture of the construction process and pre- and post-construction interviews. Using multimodal analysis, we examine these data to understand how meanings are negotiated as the maker moves iteratively among multiple representations and through semiotic choices within these representations to explain the science concept. The analyses illustrate the complexity of the construction process while providing insight into the creator’s decision-making and to her developing semiotic and conceptual understandings. These findings allow us to build on the concept of cumulative semiotic progression (Hoban & Nielsen, Research in Science Education, 35, 1101-1119, 2013) by explicating the role of iterative reasoning in the production of pedagogic multimedia.
Penetration of COVID-19 Related Terminology into Legal, Medical, and Journalistic Discourses
Authors: Trzaskawka Paula , Kic-Drgas Joanna
Published: January 2022

March 2020 has become a moment of change in communication mode and quality. Previously, the media paid attention to the current affairs, however, never earlier the journalistic discourse has been so influentially affected by the ongoing phenomenon as in the case of COVID-19. Almost overnight the new terminological phenomena with specific legal or medical reference were introduced into everyday language mainly via mass media and become an important part of a pandemic related narration. The strong influence on the shape of the mentioned linguistic changes has mainly the adoption of new legal regulations due to the unexpected outbreak of the pandemic. The aim of the following paper is to investigate how COVID-19 pandemic affected the specialisation of the journalistic discourse and how different domains (law, medicine) are being influenced by new terminology and in other way round, how for example law and medicine influence new “COVID language”. In order to take the interdisciplinary nature of the issue into account, the degree of hybridity of the selected texts will be examined by means of selected material analysis. The methodology applied in the paper uses an empirical approach and comparative analysis. The material used for the analysis comes from the selected Polish quality and boulevard press. The paper concerns the linguistic influence of the “invisible enemy” on the language presented in press. The main findings reveal the intense use of neologisms, borrowings, and it shows that the discourse was changed linguistically thanks to Student’s t-test.
Embodied Institutions and Epistemic Exclusions: Affect in the Academy
Authors: Churcher Millicent
Published: January 2022

This paper explores the intersection between affect, emotion, social imaginaries, and institutions through the lens of epistemic power in the academy. It argues that attending to this intersection is critical for a fuller understanding of how affective and emotional dynamics can assist to entrench, but also disrupt, asymmetries of epistemic privilege that cut across lines of race, sex, and other markers of social difference. As part of this discussion the paper reflects on the possibility of intervening in dominant social imaginaries that become sedimented in the routine operations of the modern university, and which produce affective ecologies that sustain epistemic exclusions within academic institutions.
Strategies That Promote Equity in COVID-19 Vaccine Uptake for Black Communities: a Review
Authors: Dada Debbie , Djiometio Joseph Nguemo , McFadden SarahAnn M. , Demeke Jemal , Vlahov David , Wilton Leo , Wang Mengzu , Nelson LaRon E.
Published: January 2022

Black communities have had a high burden of COVID-19 cases, hospitalizations, and death, yet rates of COVID-19 vaccine uptake among Blacks lag behind other demographic groups. This has been due in part to vaccine hesitancy and multi-level issues around access to COVID-19 vaccines. Effective strategies to promote vaccine uptake among Black communities are needed. To perform a rapid review covering December 2020–August 2021, our search strategy used PubMed, Google, and print media with a prescribed set of definitions and search terms for two reasons: there were limited peer-reviewed studies during the early period of vaccine roll-out and real-time perspectives were crucially needed. Analyses included expert opinion, descriptions of implemented projects, and project outcomes. The strategies described in these reports largely converged into three categories: (a) addressing mistrust, (b) combatting misinformation, and (c) improving access to COVID-19 vaccines. When working to reduce hesitancy, it is important to consider messaging content, messengers, and location. To address mistrust, reports detailed the importance of communicating through trusted channels, validating the real, history- and experience-based reasons why people may be hesitant to establish common ground, and addressing racism embedded within the healthcare system. To combat misinformation, strategies included dispelling myths and answering questions through town halls and culturally intelligent outreach. Black physicians and clinicians are considered trusted messengers and partnering with community leaders such as pastors can help to reach more people. The settings of vaccination sites should be convenient and trusted such as churches, barbershops, and community sites. While a number of individual and combination efforts have been developed and implemented, data that disentangle components that are the most effective are sparse. This rapid review provides a basis for developing strategic implementation to increase COVID-19 vaccine uptake in this ongoing pandemic and planning to promote health equity for future bio-events and health crises.
Data protection rules applicable to Financial Intelligence Units: still no clarity in sight
Authors: Quintel Teresa
Published: January 2022

Financial information can play a key role in tackling money laundering, terrorist financing and combatting serious crime more generally. Preventing and fighting money laundering and the financing of terrorism were top priorities of the European Union’s (EU) Security Strategy for 2020-2025, which might explain the fast developments regarding legislative measures to further regulate anti-money laundering (AML) and counter terrorism financing (CTF). In May 2020, the European Commission put forward an Action Plan to establish a Union policy on combatting money laundering and shortly afterwards, proposed a new AML Package.

Financial Intelligence Units (FIUs) play a crucial role in analysing and exchanging information concerning unusual and suspicious transactions, serving as intermediaries between the private sector and law enforcement authorities (LEAs). Such information includes personal data, which is protected under the EU data protection acquis. The latter is constituted of two main laws, the General Data Protection Regulation (GDPR), which applies to general processing and the so-called Law Enforcement Directive (LED) that is applicable when competent law enforcement authorities process personal data for law enforcement purposes.

This Article argues that the current legal framework on AML and CTF legislation is unclear on the data protection regime that applies to the processing of personal data by FIUs and that the proposed AML Package does little or nothing to clarify this dilemma. In order to contribute to the discussion on the applicable data protection framework for FIUs, the assessment puts forward arguments for and against the application of the LED to such processing, taking into account the relevant legal texts on AML and data protection.
Grundlagen der Injektion mittels Soft-Tissue-Filler
Authors: Sattler Sonja , Lübberding Stefanie
Published: January 2022

Injektionen mit Soft-Tissue-Fillern, insbesondere Hyaluronsäure, gehören heute zu den beliebtesten minimal-invasiven Behandlungsmethoden der Gesichtsverjüngung. Mit zunehmendem Verständnis der anatomischen Hautstrukturen und dem Wissen über die Physiologie der Hautalterung haben sich gezielt Behandlungsstrategien und -methoden entwickelt, um Patienten nach ihren Wünschen so optimal wie möglich zu behandeln. Grundlegend können Patienten entsprechend ihrem Behandlungswunsch in die Kategorien Prophylaxe, Optimierung oder Regeneration eingeteilt werden. Der Markt an Füllpräparaten liefert für jedes Behandlungsziel geeignete Präparate. Dieser Beitrag gibt einen grundlegenden Überblick zur Gewebeaugmentation mit Füllpräparaten und gibt Anregungen, um sichere Behandlungen mit optimalem Ergebnis strukturiert zu planen und durchzuführen.
Variability in phosphite sensitivity observed within and between seven Phytophthora species
Authors: Hunter Shannon , McDougal Rebecca , Williams Nari , Scott Peter
Published: January 2022

Phosphite is used to control and manage many phytophthora diseases in horticultural systems worldwide and natural ecosystems in Australia, Africa, New Zealand and parts of Northern America and Europe. Phosphite does not kill Phytophthora species, but inhibits growth while also stimulating host defence responses. Phytophthora species differ in their underlying tolerance to phosphite and isolates have been shown to acquire tolerance after prolonged exposure. Intra- and inter-specific variability in phosphite sensitivity is of interest to determine the efficacy and sustainability of phosphite for the treatment of phytophthora diseases, which continue to spread globally. Seven Phytophthora species were tested for their sensitivity to phosphite in vitro in a mycelial growth experiment. Phytophthora agathidicida was the species most sensitive to phosphite, being inhibited by 98.7% on average at the lowest phosphite treatment (15 µg/mL phosphite), followed by P. aleatoria, P. cinnamomi, P. pluvialis, P. multivora, P. kernoviae and P. citricola. Huge intraspecific variability was observed with P. kernoviae, which raises the question of whether diseases caused by P. kernoviae such as phytophthora needle blight of Pinus radiata could be managed effectively with phosphite. Further work is required to determine the phosphite sensitivity of different introduced and native Phytophthora species growing in key hosts and whether tolerance observed in vitro is also expressed in vivo.
Simulation-based decision-making system for optimal mine production plan selection
Authors: Savolainen Jyrki , Rakhsha Ramin , Durham Richard
Published: January 2022

Price uncertainty is one of the major uncertainties in the life of mine (LOM) planning process which can have a decisive effect on the overall profitability. Today’s mine planning software tools provide block-sequencing optimisation for a given static price assumption that is then used as a basis of managerial decision-making process. This paper proposes a complementary approach to this by introducing a simulation-based decision-making tool that, with the help of simulation, seeks for the optimal mine plan when a managerially estimated price development with minimum and maximum boundaries is used as a data input for the given period. To demonstrate the approach, a realistic gold mine case study is presented with five alternative and technically feasible mine plans calculated in a static optimiser from a commercial mine planning software package. These mine planning scenarios are then subjected to price uncertainty in simulation with and without a price trend assumption to highlight the effect of price on the mine’s expected performance. Based on the results, we derive and demonstrate a simulation-based system that automates the matching of optimal mine plan with the managerial insight of long-term price development.