bluuebunny/crossref_metadata_2025 huggingface dataset:
Mirtazapine in schizophrenia – an undeservedly overlooked option?
Authors: Terevnikov Viacheslav , Joffe Grigori
Published: March 2022

Mirtazapine has often been prescribed as add-on treatment for schizophrenia in patients with suboptimal response to conventional treatments. In this review, we evaluate the existing evidence for efficacy and effectiveness of add-on mirtazapine in schizophrenia and reappraise the practical and theoretical aspects of mirtazapine-antipsychotic combinations. In randomized controlled trials (RCTs), mirtazapine demonstrated favourable effects on negative and cognitive (although plausibly not depressive) symptoms, with no risk of psychotic exacerbation. Mirtazapine also may have a desirable effect on antipsychotic-induced sexual dysfunction, but seems not to alleviate extrapyramidal symptoms, at least if combined with second-generation antipsychotics. It is noteworthy that all published RCTs have been underpowered and relatively short in duration. In the only large pragmatic effectiveness study that provided analyses by add-on antidepressant, only mirtazapine was associated with both decreased rate of hospital admissions and number of in-patient days. Mirtazapine hardly affects the pharmacokinetics of antipsychotics. However, possible pharmacodynamic interactions (sedation and metabolic offence) should be borne in mind. The observed desired clinical effects of mirtazapine may be due to its specific receptor-blocking properties. Alternative theoretical explanations include its possible neuroprotective effect. Further well-designed RCTs and real-world effectiveness studies are needed to determine whether add-on mirtazapine should be recommended for difficult-to-treat schizophrenia.
Intergroup conflict: origins, dynamics and consequences across taxa
Authors: De Dreu Carsten K. W. , Triki Zegni
Published: April 2022

Although uniquely destructive and wasteful, intergroup conflict and warfare are not confined to humans. They are seen across a range of group-living species, from social insects, fishes and birds to mammals, including nonhuman primates. With its unique collection of theory, research and review contributions from biology, anthropology and economics, this theme issue provides novel insights into intergroup conflict across taxa. Here, we introduce and organize this theme issue on the origins and consequences of intergroup conflict. We provide a coherent framework by modelling intergroup conflicts as multi-level games of strategy in which individuals within groups cooperate to compete with (individuals in) other groups for scarce resources, such as territory, food, mating opportunities, power and influence. Within this framework, we identify cross-species mechanisms and consequences of (participating in) intergroup conflict. We conclude by highlighting crosscutting innovations in the study of intergroup conflict set forth by individual contributions. These include, among others, insights on how within-group heterogeneities and leadership relate to group conflict, how intergroup conflict shapes social organization and how climate change and environmental degradation transition intergroup relations from peaceful coexistence to violent conflict.

This article is part of the theme issue ‘Intergroup conflict across taxa’.
Evolution of warfare by resource raiding favours polymorphism in belligerence and bravery
Authors: Mullon Charles , Lehmann Laurent
Published: April 2022

From protists to primates, intergroup aggression and warfare over resources have been observed in several taxa whose populations typically consist of groups connected by limited genetic mixing. Here, we model the coevolution between four traits relevant to this setting: (i) investment into common-pool resource production within groups (helping); (ii) proclivity to raid other groups to appropriate their resources (belligerence); and investments into (iii) defense and (iv) offense of group contests (defensive and offensive bravery). We show that when traits coevolve, the population often experiences disruptive selection favouring two morphs: ‘Hawks’, who express high levels of both belligerence and offensive bravery; and ‘Doves’, who express neither. This social polymorphism involves further among-traits associations when the fitness costs of helping and bravery interact. In particular, if helping is antagonistic with both forms of bravery, coevolution leads to the coexistence of individuals that either: (i) do not participate into common-pool resource production but only in its defense and appropriation (Scrounger Hawks) or (ii) only invest into common pool resource production (Producer Doves). Provided groups are not randomly mixed, these findings are robust to several modelling assumptions. This suggests that inter-group aggression is a potent mechanism in favouring within-group social diversity and behavioural syndromes.

This article is part of the theme issue ‘Intergroup conflict across taxa’.
Correlates of individual participation in boundary patrols by male chimpanzees
Authors: Massaro Anthony P. , Gilby Ian C. , Desai Nisarg , Weiss Alexander , Feldblum Joseph T. , Pusey Anne E. , Wilson Michael L.
Published: April 2022

Group territory defence poses a collective action problem: individuals can free-ride, benefiting without paying the costs. Individual heterogeneity has been proposed to solve such problems, as individuals high in reproductive success, rank, fighting ability or motivation may benefit from defending territories even if others free-ride. To test this hypothesis, we analysed 30 years of data from chimpanzees (Pan troglodytes) in the Kasekela community, Gombe National Park, Tanzania (1978–2007). We examined the extent to which individual participation in patrols varied according to correlates of reproductive success (mating rate, rank, age), fighting ability (hunting), motivation (scores from personality ratings), costs of defecting (the number of adult males in the community) and gregariousness (sighting frequency). By contrast to expectations from collective action theory, males participated in patrols at consistently high rates (mean ± s.d. = 74.5 ± 11.1% of patrols,n= 23 males). The best predictors of patrol participation were sighting frequency, age and hunting participation. Current and former alpha males did not participate at a higher rate than males that never achieved alpha status. These findings suggest that the temptation to free-ride is low, and that a mutualistic mechanism such as group augmentation may better explain individual participation in group territorial behaviour.

This article is part of the theme issue ‘Intergroup conflict across taxa’.
Screening of plasma IL-6 and IL-17 in Bangladeshi lung cancer patients
Authors: Shill Manik Chandra , Biswas Bisshojit , Islam Moriam , Rima Sharmin Sultana , Ferdausi Farhana Afrin , Chowdhury Qamruzzaman , Reza Hasan Mahmud , Bepari Asim Kumar
Published: March 2022

Cancer is the second leading cause of death globally, where most cancer deaths occur in low- and middle-income countries. Lung cancer is the most prevalent in men and the third most prevalent in women among all cancer types. Globally, 1.8 million new lung cancer cases were recorded in 2012, which increased to 2 million in 2018. Cancer disease burden can be diminished, and life expectancy profoundly increases when diagnosis and prognosis are made at an earlier stage. Although biopsy is the gold standard in cancer diagnosis, it is invasive, inconvenient, and expensive. Liquid biopsy, which identifies cancer biomarkers in blood, is an active area of cancer research. Recent evidence suggests that interleukins (ILs), a class of cytokines involved in diverse cellular processes such as inflammation, growth, and proliferation, play critical roles in cancer initiation, progression, and resistance to therapy. Interestingly, many studies found the association of plasma IL-6 and IL-17 levels with lung cancer prognosis. In this study, we analyzed plasma levels of IL-6 and IL-17 in lung cancer patients and healthy volunteers. We have also studied the demographic and medical records of the participants. Among the participants, 42.9% and 57.1% were female in the control group and the disease group, respectively. The age of the participants was 22-65 years, with a mean of 46.5 (SD, ± 19.7) years. Plasma IL-6 levels were strikingly different between healthy volunteers (mean ± SEM, 0.97 ± 0.15 pg/mL) and patients (mean ± SEM, 7.42 ± 1.45 pg/mL). Notably, the range was narrow in the control group (0.32-2.10 pg/mL) but wide in the disease group (0.42-23.20 pg/mL). Plasma IL-17 levels were slightly lower in the disease group (mean ± SEM, 9.40 ± 2.82 pg/mL) compared to the control group (mean ± SEM, 12.40 ± 4.41 pg/mL), although the difference was not statistically significant. Intriguingly, the mean IL-17 value reduced dramatically with chemotherapy, and further reduction occurred with radiotherapy in lung cancer patients. Together, our study supports the use of plasma IL-6 and IL-7 levels as prognostic markers in lung cancer.
Optimal epidemic control under uncertainty: trade-offs between information collection and other actions
Authors: Flaig Julien , Houy Nicolas
Published: March 2022

Background

Recent epidemics and measures taken to control them – through vaccination or other actions – have highlighted the role and importance of uncertainty in public health. There is generally a trade-off between information collection and other uses of resources. Whether this trade-off is solved explicitly or implicitly, the concept of value of information is central in order to inform policy makers in an uncertain environment.

Method

We use a deterministic SIR disease emergence and transmission model with vaccination that can be administered as one or two doses. The disease parameters and vaccine characteristics are uncertain. We study the trade-offs between information acquisition and two other measures: bringing vaccination forward, and acquiring more vaccine doses. To do this, we quantify the expected value of perfect information (EVPI) under different constraints faced by public health authorities,i.e. the time of the vaccination campaign implementation and the number of vaccine doses available.

Results

We discuss the appropriateness of different responses under uncertainty. We show that in some cases, vaccinating later or with less vaccine doses but more information about the epidemic and the efficacy of control strategies may bring better results than vaccinating earlier or with more doses and less information respectively

Conclusion

In the present methodological paper, we show in an abstract setting how clearly defining and treating the trade-off between information acquisition and the relaxation of constraints can improve public health decision making.

Highlights

Uncertainties can seriously hinder epidemic control, but resolving them is costly. Thus there are trade-offs between information collection and alternative uses of resources.

We use a generic SIR model with vaccination and a value of information framework to explore these trade-offs.

We show in which cases vaccinating later with more information about the epidemic and the efficacy of control measures may be better – or not – than vaccinating earlier with less information.

We show in which cases vaccinating with less vaccine doses and more information about the epidemic and the efficacy of control measures may be better – or not – than vaccinating with more doses and less information.
Systematic literature review examining the mere-measurement effect of patient reported measures: the interaction of emotional valence and frequency of exposure as an independent factor in patient change
Authors: Long Preston , Ritschl Valentin , Otto Lisa , Rogge Alize , Koppert Linetta , Huberts Anouk , Stamm Tanja
Published: March 2022

The use of patient-reported outcome (PROs) have become increasingly commonplace across many healthcare settings over the past two decades. The value of PROs is now acknowledged by healthcare providers and patients alike. However, to date, little is known about the best practices for formulating PRO measures (PROMS), but even more specifically, the effect had on the responding patients as a result of item word choice, emotional valence, or frequency of use. That is, 1) does the positive or negative wording of items affect the patient’s perspective on the latent variable, 2) is there a degree of subliminal influence or measurement effects on their behaviour resulting from exposure to PROs, and finally, 3) is such an effect amplified with repeated exposure?
Understanding Barriers toward Interventions for Childhood Obesity in Minority Communities: A Rapid Review
Authors: Colvin Kenya M.
Published: March 2022

Background

It is well documented that racial/ethnic minorities have higher attrition rates from pediatric weight manage programs than their white counterparts. This review aimed to identify barriers facing minority families when seeking to complete weight management programs for their children to develop strategies to keep these families engaged. Maintaining engagement through program completion could improve health outcomes and overall quality of life for minority children.

Methods

Eligible studies were identified through searching PubMed, PsychINFO and CENTRAL databases. Articles had to focus on reasons for attrition from pediatric weight management among minority groups to be included. We extracted data on attrition from each study and narratively summarized the results.

Results

From the 302 articles screened, five met the inclusion criteria. Four of the five studies predicted attrition factors from attendance or past survey data. Only one study surveyed parents to identify potential barriers. Among these studies, most sociodemographic factors analyzed had no significant effect on early dropout. Program structure, logistical barriers, and parental negative self and child body image were all identified as predictors of attrition.

Conclusion

More studies need to directly investigate why minority families discontinue weight management treatments early. Directly interviewing or surveying parents to ascertain their concerns can lead to the development of programs that retain and better meet the needs of these groups.
Adherence to and enforcement of non-pharmaceutical interventions (NPIs) for COVID-19 prevention in Nigeria, Rwanda, and Zambia: A mixed-methods analysis
Authors: Solomon Hiwote , Thea Donald M. , Galea Sandro , Sabin Lora L. , Lucey Daniel R. , Hamer Davidson H.
Published: March 2022

Introduction

In the early parts of the COVID-19 pandemic, non-pharmaceutical interventions (NPIs) were implemented worldwide, including in sub-Saharan Africa, to prevent and control SARS-CoV-2 transmission. This mixed-methods study examines adherence to and enforcement of NPIs implemented to curb COVID-19 in Nigeria, Rwanda, and Zambia, leading up to the 10,000th case of laboratory-confirmed COVID-19 in each country. Additionally, we aim to evaluate the relationship between levels and changes of NPIs over time and changes in COVID-19 cases and deaths.

Methods

This mixed-methods analysis utilized semi-structured interviews and a quantitative dataset constructed using multiple open data sources, including the Oxford COVID-19 Government Response Tracker. To understand potential barriers and facilitators in implementing and enforcing NPIs qualitative data were collected from those involved in the COVID-19 response and analyzed using NVivo. Quantitative results were analyzed using descriptive statistics, plots, ANOVA, and post hoc Tukey.

Results

Individual indicator scores varied with the COVID-19 response in all three countries. Nigeria had sustained levels of strict measures for containment and closure NPIs, while in Rwanda there was substantial variation in NPI score as it transitioned through the different case windows for the same measures. Zambia implemented moderate stringency throughout the pandemic using gathering restrictions and business/school closure measures but maintained low levels of strictness for other containment and closure measures. Rwanda had far more consistent and stringent measures compared to Nigeria and Zambia. Rwanda’s success in implementing COVID-related measures was partly due to strong enforcement and having a population that generally obeys its government.

Conclusion

Various forces either facilitated or hindered adherence and compliance to COVID-19 control measures. This research highlights important lessons, including the need to engage communities early and create buy-in, as well as the need for preparation to ensure that response efforts are proactive rather than reactive when faced with an emergency.
Human gain-of-function variants in HNF1A confer protection from diabetes but independently increase hepatic secretion of multiple cardiovascular disease risk factors
Authors: DeForest Natalie , Kavitha Babu , Hu Siqi , Isaac Roi , Wang Minxian , Du Xiaomi , De Arruda Saldanha Camila , Gylys Jenny , Abagyan Ruben , Najmi Laeya , Mohan Viswanathan ,   Alnylam Human Genetics,   AMP-T2D Consortium, Flannick Jason , Peloso Gina M. , Gordts Philip , Heinz Sven , Deaton Aimee M. , Khera Amit V. , Olefsky Jerrold , Radha Venkatesan , Majithia Amit R.
Published: March 2022

Loss-of-function mutations in Hepatocyte Nuclear Factor 1A (HNF1A) are known to cause rare forms of diabetes and alter hepatic physiology through unclear mechanisms. In the general population, 1:100 individuals carry a rare protein-coding variant in HNF1A, most of unknown functional consequence. To characterize the full allelic series, we performed deep mutational scanning of 11,970 protein-coding HNF1A variants in human hepatocytes and clinical correlation with 553,246 exome-sequenced individuals. Surprisingly, we found ∼1:5 rare protein-coding HNF1A variants found in the general population cause molecular gain-of-function (GOF), increasing the transcriptional activity of HNF1A by up to 50%. GOF in HNF1A conferred protection from type 2 diabetes (T2D) (OR=0.60, p=8.4 x 10-7), but not against coronary artery disease. Independently of T2D, increased hepatic expression of HNF1A promoted a pro-inflammatory and pro-atherogenic serum profile mediated in part by enhanced transcription of risk genes including PCSK9. In summary, ∼1:300 individuals carry a GOF variant in HNF1A that protects carriers from diabetes but enhances hepatic secretion of metabolic disease risk factors.
High-throughput imaging and quantitative analysis uncovers the nature of plasmid positioning by ParABS
Authors: Köhler Robin , Murray Seán M.
Published: March 2022

The faithful segregation and inheritance of bacterial chromosomes and low-copy number plasmids requires dedicated partitioning systems. The most common of these, ParABS, consists of ParA, a DNA-binding ATPase and ParB a protein that binds to centromeric-like parS sequences on the DNA cargo. The resulting nucleoprotein complexes are believed to move up a self-generated gradient of nucleoid-associated ParA. However, it remains unclear how this leads to the observed cargo positioning and dynamics. In particular, the evaluation of models of plasmid positioning has been hindered by the lack of quantitative measurements. Here, we use high-throughput imaging, analysis and modelling to determine the dynamical nature of these systems. We find that F plasmid is actively brought to specific subcellular home positions within the cell with dynamics akin to an over-damped spring. We identify ParA hopping on the nucleoid as the primary determinant of this geometry-sensing and develop a unified computational model that quantitatively explains the observed behaviour. Furthermore, we confirm our model prediction that cells with the lowest plasmid concentration transition to oscillatory dynamics and find similar behaviour in a distantly-related ParABS system. Our results indicate that ParABS regularly positions plasmids across the nucleoid but operates just below the threshold of an oscillatory instability, minimising ATP consumption. Overall, this work uncovers the dynamical nature of plasmid positioning by ParABS and provides insights relevant for chromosome-based systems.
Ptbp1 knockdown in mouse striatum did not induce astrocyte-to-neuron conversion using HA-tagged labeling system
Authors: Yang Guixiang , Yan Zixiang , Wu Xiaoqing , Zhang Meng , Xu Chunlong , Shi Linyu , Yang Hui , Fang Kailun
Published: March 2022

Conversion of astrocytes to neurons (AtN) is a promising potential strategy for the treatment of neurodegenerative diseases. Recent studies have reported that shRNA-, CasRx-, or ASO-mediated Ptbp1 suppression could reprogram resident astrocytes to neurons1–3. However, some groups have disputed the data interpretation of the reported AtN conversion events4–7. These controversies surrounding AtN conversion may due to differences in the astrocyte fate-mapping systems they applied from that in the original study, i.e., recombinant mouse strains with astrocyte specific reporter constructs versus AAV-based labeling systems. Here, we applied AAV-based tracing systems to label astrocytes with GFAP-driven HA-tagged Cas13X (AAV-GFAP::Cas13X-NLS-HA-sgPtbp1). Compared to GFAP-driven tdTomato reporter (AAV-GFAP::tdTomato) system in previous studies, we found no AtN conversion in mouse striatum. Furthermore, no intermediate neurons and no neuron density increase suggested no AtN conversion. Our findings indicated that inconsistent AtN outcomes may arise from different fate-mapping systems between AAV and transgenic mice, as well as through use of different reporter proteins. Thus, the complexity of astrocyte labeling systems warrants careful attention when drawing conclusions about whether AtN conversion occurs.
Effect of seizures on developmental trajectories in children with autism
Authors: Forman Phillip , Khokhlovich Edward , Vyshedskiy Andrey
Published: March 2022

The effect of seizures in 2 to 5-year-old children with ASD was investigated in the largest and the longest observational study to-date. Parents assessed the development of 8461 children quarterly for three years on five orthogonal subscales: combinatorial receptive language, expressive language, sociability, sensory awareness, and health. Seizures were reported in 11% of children. Children with no seizures developed faster compared to matched children with seizures in all subscales. On an annualized basis, participants with no seizures improved their receptive language 1.5-times faster than those with seizures; expressive language: 1.3-times faster; sociability: 2.3-times faster; sensory awareness: 6.2-times faster; and health: 20.0-times faster. This study confirms a high prevalence of seizures in ASD children and points to the need for more systematic approach to the development of treatment strategies.
Jumping out of trouble: Evidence for a cognitive map in guppies (Poecilia reticulata)
Authors: de Waele Hannah , Pouca Catarina Vila , van Boerdonk Dimphy , Luiten Ewoud , Leenheer Lisanne M. , Mitchell David , Vega-Trejo Regina , Kotrschal Alexander
Published: March 2022

Spatial cognitive abilities allow individuals to remember the location of food patches, predator hide-outs, or shelters. Animals typically incorporate learnt spatial information or use external environmental cues to navigate their surroundings. A spectacular example of how some fishes move is through aerial jumping. For instance, fish that are trapped within isolated pools, cut off from the main body of water during dry periods, may jump over obstacles and direct their jumps to return to safe locations. However, what information such re-orientation behaviour during jumping is based on remains enigmatic. Here we combine a lab and field experiment to test if guppies (Poecilia reticulata) incorporate learnt spatial information and external environmental cues (visual and auditory) to determine where to jump. In a spatial memory assay we found that guppies were more likely to jump towards deeper areas, hence incorporating past spatial information to jump to safety. In a matched vs. mismatched spatial cue experiment in the field, we found that animals only showed directed jumping when visual and auditory cues matched. We show that in unfamiliar entrapments guppies direct their jumps by combining visual and auditory cues, while in familiar entrapments they use a cognitive map. We hence conclude that jumping behaviour is a goal-directed behaviour, guided by different sources of information and involving important spatial cognitive skills.
Obligate sexual reproduction of a homothallic fungus closely related to the Cryptococcus pathogenic species complex
Authors: Passer Andrew Ryan , Clancey Shelly Applen , Shea Terrance , David-Palma Márcia , Averette Anna Floyd , Boekhout Teun , Porcel Betina M. , Nowrousian Minou , Cuomo Christina A. , Sun Sheng , Heitman Joseph , Coelho Marco A.
Published: March 2022

Sexual reproduction is a ubiquitous and ancient trait of eukaryotic life. While sexual organisms are usually faced with the challenge of finding a compatible mating partner, species as diverse as animals, plants, and fungi have repeatedly evolved the ability to reproduce sexually without an obligate requirement for another individual. Here, we uncovered the underlying mechanism of self-compatibility (homothallism) in Cryptococcus depauperatus, a fungal species sister to the clinically relevant human fungal pathogens Cryptococcus neoformans and Cryptococcus gattii species complexes. In contrast to C. neoformans or C. gattii, which grow as a yeast in the asexual stage, and produce hyphae, basidia, and infectious spores during the sexual stage, C. depauperatus grows exclusively as hyphae decorated with basidia and abundant spores and appears to be continuously engaged in sexual reproduction. By combining the insights from comparative genomics and genetic analyses of mutants defective in key mating and meiosis genes, we demonstrate the sexual cycle of C. depauperatus involves meiosis, and reveal that self-compatibility is orchestrated by the expression, in the same cell, of an unlinked mating receptor (Ste3a) and pheromone ligand (MFα) pair seemingly derived from opposite mating types of a heterothallic (self-sterile) ancestor. We identified a putative mating-type (MAT) determining region containing genes phylogenetically aligned with MATa alleles of other species, and a few MATα gene alleles scattered and unlinked throughout the genome, but no homologs of the mating-type homeodomain genes SXI1 (HD1) and SXI2 (HD2). Comparative genomic analyses suggested a dramatic remodeling of the MAT locus possibly owing to reduced selective constraints to maintain mating-type genes in tight linkage, associated with a transition to self-fertility. Our findings support C. depauperatus as an obligately sexual, homothallic fungal species and provide additional insight into the repeated transitions between modes of sexual reproduction that have occurred throughout the fungal kingdom.
Nitrite lowers the oxygen cost of ATP supply in skeletal muscle cells by stimulating the rate of glycolytic ATP synthesis
Authors: Wynne Anthony G. , Affourtit Charles
Published: March 2022

Dietary nitrate lowers the oxygen cost of human exercise. This effect has been suggested to result from stimulation of coupling efficiency of skeletal muscle oxidative phosphorylation by reduced nitrate derivatives. In this paper, we report the acute effects of sodium nitrite on the bioenergetic behaviour of L6 myocytes. At odds with improved efficiency of mitochondrial ATP synthesis, extracellular flux analysis reveals that a ½-hour exposure to NaNO2 (0.1 – 5 µM) significantly decreases mitochondrial coupling efficiency in static myoblasts and tends to lower it in spontaneously contracting myotubes. Unexpectedly, NaNO2 stimulates the rate of glycolytic ATP production in both myoblasts and myotubes. Increased ATP supply through glycolysis does not emerge at the expense of oxidative phosphorylation, which means that NaNO2 acutely increases the rate of overall myocellular ATP synthesis, highly significantly so in myoblasts and tending towards significance in contractile myotubes. Notably, NaNO2 exposure shifts myocytes to a more glycolytic phenotype. Mitochondrial oxygen consumption does not decrease after NaNO2 exposure, and non-mitochondrial respiration tends to drop. When total ATP synthesis rates are normalised to total cellular oxygen consumption rates, it thus transpires that NaNO2 lowers the oxygen cost of ATP supply in L6 myocytes.
3D Organic Bioelectronics for Monitoring In Vitro Stem Cell Cultures
Authors: Savva Achilleas , Saez Janire , Barberio Chiara , Lu Zixuan , Moysidou Chrysanthi-Maria , Kallitsis Konstantinos , Withers Aimee , Pitsalidis Charalampos , Owens Róisín M.
Published: March 2022

Three-dimensional in vitro stem cell models has enabled a fundamental understanding of cues that direct stem cell fate and be used to develop novel stem cell treatments. While sophisticated 3D tissues can be generated, technology that can accurately monitor these complex models in a high-throughput and non-invasive manner is not well adapted. Here we show the development of 3D bioelectronic devices based on the electroactive polymer poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) - PEDOT:PSS and their use for non-invasive, electrical monitoring of stem cell growth. We show that the electrical, mechanical and wetting properties as well as the pore size/architecture of 3D PEDOT:PSS scaffolds can be fine-tuned simply by changing the processing crosslinker additive. We present a comprehensive characterization of both 2D PEDOT:PSS thin films of controlled thicknesses, and 3D porous PEDOT:PSS structures made by the freeze-drying technique. By slicing the bulky scaffolds we show that homogeneous, porous 250 um thick PEDOT:PSS slices are produced, generating biocompatible 3D constructs able to support stem cell cultures. These multifunctional membranes are attached on Indium-Tin oxide substrates (ITO) with the help of an adhesion layer that is used to minimize the interface charge resistance. The optimum electrical contact result in 3D devices with a characteristic and reproducible, frequency dependent impedance response. This response changes drastically when human adipose derived stem cells grow within the porous PEDOT:PSS network as revealed by fluorescence microscopy. The increase of these stem cell population within the PEDOT:PSS porous network impedes the charge flow at the interface between PEDOT:PSS and ITO, enabling the interface resistance to be extracted by equivalent circuit modelling, used here as a figure of merit to monitor the proliferation of stem cells. The strategy of controlling important properties of 3D PEDOT:PSS structures simply by altering processing parameters can be applied for development of a number of stem cell in vitro models. We believe the results presented here will advance 3D bioelectronic technology for both fundamental understanding of in vitro stem cell cultures as well as the development of personalized therapies.
Telehealth versus Self-Directed Lifestyle Intervention to Promote Healthy Blood Pressure: a Randomized Controlled Trial
Authors: Chang Alex R , Gummo Lauren , Yule Christina , Bonaparte Heather , Collins Charlotte , Naylor Allison , Appel Lawrence , Juraschek Stephen P , Bailey-Davis Lisa
Published: April 2022

Introduction

Lifestyle behavior modification interventions, delivered using telehealth, have been shown to be effective in reducing weight. However, limited data exists on the benefits of lifestyle behavior change delivered using telehealth and web-based applications on blood pressure (BP).

Methods

We conducted a 2-site randomized controlled trial in the Geisinger Health System (January 2019 to March 2021) to compare the efficacy of a self-guided vs. a dietitian telehealth approach using web-based applications in 187 participants with 24-hour systolic BP 120-160 mmHg and body mass index ≥ 25 kg/m2. Both arms received recommendations to improve diet based on a web-based food frequency questionnaire, and access to an online weight management program. The telehealth arm received weekly telephone calls with a dietitian who used motivational interviewing. The primary outcome was 12-week change in 24-hour systolic BP. Secondary outcomes included changes in sleep/awake systolic BP and diastolic BP, self-reported physical activity, healthy eating index (HEI)-2015 score, and weight.

Results

A total of 187 participants (mean age 54.6 [SD 13.2] years, 52% female, 23% on BP medications, mean body mass index 34.5 [6.5] kg/m2, mean HEI-2015 score 60.8 [11.1] units) were randomized with 156 (83.4%) completing the trial. Mean 24-hour systolic BP improved from baseline to 12 weeks similarly in the dietitian (−6.73 mmHg, 95% CI: −8.64, −4.82) and the self-directed arm (−4.92, 95% CI: −7.01, −2.77; p comparing groups=0.2). The dietitian telehealth arm had greater 12-week improvements in sleep systolic BP (mean −6.92 vs. −1.45; p=0.004), sleep diastolic BP (−3.31 vs. 0.73; p=0.001), and self-reported physical activity (866 vs. −243 metabolic equivalent of task minutes/week; p=0.01). The dietitian telehealth arm also tended to have greater 12-week improvements in weight loss (−5.11 vs. −3.89 kg; p=0.1) and HEI-2015 score (9.23 vs. 6.43 units; p=0.09), though these differences were not statistically significant.

Conclusions

Dietitian-led telehealth supported by web-based applications resulted in a similar reduction in 24-hour systolic BP as a self-directed approach, with secondary improvements in sleep BP and physical activity.

Trial registration number

ClinicalTrials.gov Identifier NCT03700710
WWP2 osteoarthritis risk allele rs1052429-A confers risk by affecting cartilage matrix deposition via hypoxia associated genes
Authors: Tuerlings Margo , Janssen George M.C. , Boone Ilja , van Hoolwerff Marcella , Rodriguez Ruiz Alejandro , Houtman Evelyn , Suchiman Eka H.E.D. , van der Wal Robert J.P. , Nelissen Rob G.H.H. , Coutinho de Almeida Rodrigo , van Veelen Peter A. , Ramos Yolande F.M. , Meulenbelt Ingrid
Published: March 2022

Objective

To explore the co-expression network of the osteoarthritis (OA) risk gene WWP2 in articular cartilage and study cartilage characteristics when mimicking the effect of OA risk allele rs1052429-A on WWP2 expression in a human 3D in vitro model of cartilage.

Methods

Co-expression behavior of WWP2 with genes expressed in lesioned OA articular cartilage (N=35 samples) was explored. By applying lentiviral particle mediated WWP2 upregulation in 3D in vitro pellet cultures of human primary chondrocytes (N=8 donors) the effects of upregulation on cartilage matrix deposition was evaluated. Finally, we transfected primary chondrocytes with miR-140 mimics to evaluate whether miR-140 and WWP2 are involved in similar pathways.

Results

Upon performing Spearman correlations in lesioned OA cartilage, 98 highly correlating genes (|ρ|>0.7) were identified. Among these genes, we identified GJA1, GDF10, STC2, WDR1, and WNK4. Subsequent upregulation of WWP2 on 3D chondrocyte pellet cultures resulted in a decreased expression of COL2A1 and ACAN and an increase in EPAS1 expression. Additionally, we observed a decreased expression of GDF10, STC2, and GJA1. Proteomics analysis identified 42 proteins being differentially expressed with WWP2 upregulation, which were enriched for ubiquitin conjugating enzyme activity. Finally, upregulation of miR-140 in 2D chondrocytes resulted in significant upregulation of WWP2 and WDR1.

Conclusions

Mimicking the effect of OA risk allele rs1052429-A on WWP2 expression initiates detrimental processes in the cartilage shown by a response in hypoxia associated genes EPAS1,GDF10, and GJA1 and a decrease in anabolic markers, COL2A1 and ACAN.
Decoding mitochondrial genes in pediatric AML and development of a novel prognostic mitochondrial gene signature
Authors: Chaudhary Shilpi , Ganguly Shuvadeep , Palanichamy Jayanth Kumar , Singh Archna , Pradhan Dibyabhaba , Bakhshi Radhika , Chopra Anita , Bakhshi Sameer
Published: April 2022

Background

Gene expression profile of mitochondrial-related genes is not well deciphered in pediatric acute myeloid leukaemia (AML). We aimed to identify mitochondria-related differentially expressed genes (DEGs) in pediatric AML with their prognostic significance.

Methods

Children with de novo AML were included prospectively between July 2016-December 2019. Transcriptomic profiling was done for a subset of samples, stratified by mtDNA copy number. Top mitochondria-related DEGs were identified and validated by real-time PCR. A prognostic gene signature risk score was formulated using DEGs independently predictive of overall survival (OS) in multivariable analysis. Predictive ability of the risk score was estimated along with external validation in The Tumor Genome Atlas (TCGA) AML dataset.

Results

In 143 children with AML, twenty mitochondria-related DEGs were selected for validation, of which 16 were found to be significantly dysregulated. Upregulation of SDHC (p<0.001), CLIC1 (p=0.013) and downregulation of SLC25A29 (p<0.001) were independently predictive of inferior OS, and included for developing prognostic risk score. The risk score model was independently predictive of survival over and above ELN risk categorization (Harrell’s c-index: 0.675). High-risk patients (risk score above median) had significantly inferior OS (p<0.001) and event free survival (p<0.001); they were associated with poor-risk cytogenetics (p=0.021), ELN intermediate/poor risk group (p=0.016), absence of RUNX1-RUNX1T1 (p=0.027), and not attaining remission (p=0.016). On external validation, the risk score also predicted OS (p=0.019) in TCGA dataset.

Conclusion

We identified and validated mitochondria-related DEGs with prognostic impact in pediatric AML and also developed a novel 3-gene based externally validated gene signature predictive of survival.
Associations of current and childhood socioeconomic status and health outcomes amongst patients with knee or hip osteoarthritis in a Mexico City family-practice setting
Authors: Pisanty-Alatorre Julio , Bello-Chavolla Omar Yaxmehen , Vilchis-Chaparro Eduardo , Goycochea-Robles María Victoria
Published: April 2022

Objectives

To examine the association of current and childhood socioeconomic status (SES) with patient-reported functional status, quality of life and disability in patients with knee osteoarthritis (OA)

Methods

We conducted a cross-sectional study amongst individuals seeking care for any medical reason in a primary care family-practice clinic in Mexico City. We included individuals with self-reported doctor-diagnosed arthritis and administered a survey using validated Spanish language versions of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the Osteoarthritis of Lower Limbs and Quality of Life (AMICAL), and the Stanford Health Assessment Questionnaire-Disability Index (HAQ-DI). To estimate current and childhood SES, we and used a validated tool to estimate income quintile, as well as education level and occupation type, for both the patient and their parents.

Results

We recruited 154 patients and excluded 8 patients. Estimated income and education levels were correlated with WOMAC, AMICAL and HAQ-DI scores, and significant differences were found in all scores by occupation type. The association for estimated income and all scores remained significant independently of age, sex, BMI, and presence of diabetes or hypertension. Maternal education was best correlated with AMICAL scores, though its effect seemed largely mediated by its association with current SES measures.

Conclusions

Current and – to a lesser extent – childhood Socioeconomic Status impacts functional status, quality of life and disability amongst OA patients in Mexico City. Awareness of life-course SES can help identify patients at risk for worse outcomes.
The spatial-temporal risk profiling of Clonorchis sinensis infection in South Korea: A geostatistical modeling study
Authors: Xiao Hai-Yan , Chai Jong-Yil , Fang Yue-Yi , Lai Ying-Si
Published: April 2022

Clonorchiasis is one of the major parasitic diseases in South Korea. Spatially explicit estimates of the infection risk are important for control and intervention. We did a systematic review of collected prevalence data on Clonorchis sinensis infection in South Korea. Data of potential influencing factors (e.g., environmental and social-economic factors) was obtained from open-access databases. Bivariate Bayesian geostatistical joint modeling approaches were applied to analyze disease data, within a logit regression in combination of potential influencing factors and spatial-temporal random effects. We identified surveys of C. sinensis infection done at 1362 unique locations, and presented the first spatial-temporal risk maps at high spatial resolution (5×5km) in South Korea. High infection risk areas shrunk significantly from 1970 to 2017. The overall risk decreased since the start of the national deworming program in 1969, and then slightly increased since the year 1995 when the program suspended, and maintained stable since 2005 when the Clonorchiasis Eradication Program begun. The population-weighted prevalence was estimated as 3.87% (95% BCI: 3.04-4.82%) in 2017, accounting to 1.92 (95% BCI: 1.51-2.40) million infected people. Although the prevalence over the country has been low, C. sinensis infection was still endemic in areas of eastern and southern regions, particularly the five major river basins. We also defined factors significantly correlated, such as, distance to the nearest open water bodies, annual precipitation, and land surface temperature at night. All findings above provide important information on spatial-targeting control and preventive strategies of C. sinensis infection in South Korea.
Molecular basis of neurodevelopmental disorder-causing mutation in nonsense-mediated mRNA decay factor UPF3B
Authors: Bufton Joshua C. , Powers Kyle T. , Szeto Jenn-Yeu A. , Schaffitzel Christiane
Published: April 2022

UPF3B is a key nonsense-mediated mRNA decay (NMD) factor required for surveillance of mRNA and regulation of eukaryotic gene expression. Mutations in UPF3B cause intellectual disability. The underlying molecular mechanisms remain unexplored as the mutations lie in an uncharacterized region of UPF3B. Here, we show that UPF3B shares structural and functional homology to the Drosophila Behavior/Human Splicing protein family comprising an RNA-recognition motif-like domain (RRM-L), a NONA/paraspeckle-like domain (NOPS-L), and extended α-helical domains essential for ribosome- and RNA-binding and RNA-induced oligomerization. A co-crystal structure of UPF3B with the third middle domain of eukaryotic initiation factor 4G (MIF4GIII) of UPF2 reveals an unexpectedly intimate binding interface. UPF3B’s disease-causing mutation Y160D located in the NOPS-L domain reduces the UPF2 binding affinity ~40-fold compared to wildtype UPF3B. UPF3B’s paralogue UPF3A, an NMD antagonist which is upregulated in patients with the UPF3B-Y160D mutation, binds UPF2 with ~10-fold higher affinity than UPF3B, leading to impaired NMD activity and upregulation of mRNAs involved in neurodevelopment.
Significant impacts of the COVID-19 pandemic on race/ethnic differences in USA mortality
Authors: Aburto José Manuel , Tilstra Andrea M. , Floridi Ginevra , Dowd Jennifer B.
Published: April 2022

The COVID-19 pandemic triggered declines in life expectancy at birth around the world. The United States of America (USA) was hit particularly hard among high income countries. Early data from the USA showed that these losses varied greatly by race/ethnicity in 2020, with Hispanic and Black Americans suffering much larger losses in life expectancy compared to white people. We add to this research by examining trends in lifespan inequality, average years of life lost, and the contribution of specific causes of death and ages to race/ethnic life expectancy disparities in the USA from 2010 to 2020. We find that life expectancy in 2020 fell more for Hispanic and Black males (4.5 years and 3.6 years, respectively) compared to white males (1.5 years). These drops nearly eliminated the previous life expectancy advantage for the Hispanic compared to white population, while dramatically increasing the already large gap in life expectancy between Black and white people. While the drops in life expectancy for the Hispanic population were largely attributable to official COVID-19 deaths, Black Americans additionally saw increases in cardiovascular disease and “deaths of despair” over this period. In 2020, lifespan inequality increased slightly for Hispanic and white populations, but decreased for Black people, reflecting the younger age pattern of COVID-19 deaths for Hispanic people. Overall, the mortality burden of the COVID-19 pandemic hit race/ethnic minorities particularly hard in the USA, underscoring the importance of the social determinants of health during a public health crisis.

Significance statement

Public interest in social and health inequalities is increasing. We examine the impact of COVID-19 on mortality in the USA across racial/ethnic groups and present four key findings. First, all groups suffered sizable life-expectancy losses and increases in years of life lost. Mortality from cardiovascular diseases, “deaths of despair”, and COVID-19 explained most of these losses. Second, working-age mortality accounted for substantial life-expectancy losses, especially among Hispanic males. Third, lifespan inequality increased for Hispanic and white people, but decreased slightly for Black people. Fourth, the pandemic shifted racial/ethnic mortality differentials in favor of white people: narrowing the Hispanic advantage and widening the Black disadvantage. Our results provide a comprehensive assessment of mortality trends to inform policies targeting inequalities.
Sensory spaces: sensory living – studio teaching the design of autism-friendly adult accommodation
Authors: Love Joan Scott
Published: March 2022

Purpose

The study aims to evaluate: (1) How university students from interior architecture can create a forward-looking “Sensory Living” brief informed by both external autism experts and a specialist tutor, evidenced through Leeds City Council's live autism adult accommodation project. (2) Issues involved with moving an experimental studio teaching model online during the COVID-19 pandemic.

Design/methodology/approach

A grounded theory approach informs an innovative teaching model, run over two years, to create a better normal; challenges and opportunities are critiqued.

Findings

Feedback from experienced autism-specific experts raises recurring sensory and communication issues which frame a series of design problems to help inform the student briefs. Students learn that the designer as advocate for vulnerable users is imperative. Aspects of online teaching that can benefit an experimental studio teaching model are identified.

Practical implications

Identification of the responsive “Sensory Living Model” illustrates (1) How local authorities can avoid seclusion and integrate meaningful “continuous learning opportunities” into autism-friendly adult accommodation for post-pandemic health and wellbeing. (2) How to embed autism-friendly design in the university curriculum.

Social implications

The study helps address some of the UK Government's “National strategy for autistic children, young people and adults: 2021 to 2026”.

Originality/value

“Ten Novel Sensory Living Themes” are uncovered to help inform the design of autism-friendly adult accommodation. These are of value to (1) local authorities and design practitioners in formulating design briefs and (2) universities in educating future designers of inclusive spaces.