bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of categorical matrix completion algorithms: toward improved active learning for drug discovery
Authors: Sun Huangqingbo , Murphy Robert F
Published: April 2021

Motivation

High throughput and high content screening are extensively used to determine the effect of small molecule compounds and other potential therapeutics upon particular targets as part of the early drug development process. However, screening is typically used to find compounds that have a desired effect but not to identify potential undesirable side effects. This is because the size of the search space precludes measuring the potential effect of all compounds on all targets. Active machine learning has been proposed as a solution to this problem.

Results

In this article, we describe an improved imputation method, Impute by Committee, for completion of matrices containing categorical values. We compare this method to existing approaches in the context of modeling the effects of many compounds on many targets using latent similarities between compounds and conditions. We also compare these methods for the task of driving active learning in well-characterized settings for synthetic and real datasets. Our new approach performed the best overall both in the accuracy of matrix completion itself and in the number of experiments needed to train an accurate predictive model compared to random selection of experiments. We further improved upon the performance of our new method by developing an adaptive switching strategy for active learning that iteratively chooses between different matrix completion methods.

Availability and implementation

A Reproducible Research Archive containing all data and code is available at http://murphylab.cbd.cmu.edu/software.

Supplementary information

Supplementary data are available at Bioinformatics online.
Professional Legitimacy, Identity, and Practice: Towards a Sociology of Professionalism in Probation
Authors: Tidmarsh Matt
Published: April 2021

This paper draws from Foucauldian understandings of the sociology of the professions to explore legitimacy, identity, and practice in probation after the Transforming Rehabilitation (TR) reforms to services in England and Wales. A discourse of ‘professionalism’ was crucial to the Coalition Government’s mobilization of TR; however, the contested nature of the term is rarely acknowledged in a probation context. Based on an ethnographic study of a privately-owned Community Rehabilitation Company, the paper demonstrates how professionalism in probation has been reshaped by punitive, managerial, and rehabilitative ‘adaptations’. It argues that professionalism has been detached from its ideal-typical groundings, becoming a malleable practice of (self-)government which is integral to how probation professionals demonstrate their legitimacy to multiple (and competing) actors in a network of accountability – the state, the public, offenders, adjacent organizations, and, additionally, private providers. Accordingly, appeals to a discourse of professionalism are a source of meaning for staff and a disciplinary mechanism that governs their conduct ‘at a distance’.
Carnival, Sexual Violence and Harm at Australian Music Festivals
Authors: Wadds Phillip , Fileborn Bianca , Tomsen Stephen
Published: April 2021

Much has been written about the search for carnivalesque release in late-modern society, but relatively less attention has been paid to the harms experienced within this practice. Based on mixed-methods qualitative research including observational fieldwork at a large, multi-day camping festival in NSW, Australia, and in-depth interviews with victim-survivors of sexual violence occurring at Australian music festivals, this paper considers music festivals as sites of contemporary carnival. The paper examines the way in which situational, environmental and gendered dynamics shape these transgressive experiences. In doing so, it advances cultural criminological understandings of the carnivalesque by highlighting the bounded nature of carnival and the ‘cultural scaffolding’ that enables sexual violence and harassment at music festival events.
Social Work’s Feminist Façade: Descriptive Manifestations of White Supremacy
Authors: Hall Ronald E
Published: April 2021

Inspired by Queen Elizabeth I’s Poor Laws, Jane Addams espoused the rhetoric of social justice. Addams is an example of social reform between 1890 and 1930s as tied to eugenics, which is also evident in disagreements between Addams and Ida B. Wells. Despite the contributions of white women to social work, their subtle transgressions exist behind the veil of a feminist façade. It operates as a culture of ideas, and ultimately a prescribed assortment of race-based behaviours. Leading white women such as Addams dedicated their careers aloof to the subjugation of non-white issues that Ida B. Wells challenged via lynching. After constant prodding from Wells, Addams emerged from her silence to oppose lynching. Wells responded to Addams’ discourse that she viewed as passive white rhetoric. According to contemporary descriptive data, white women/students are similarly aloof to non-white issues provoking womanism in response to feminism’s Women’s Ku Klux Klan. Ultimately, in the rescue of social justice, white women activists, including Social Work students, must denounce the feminist façade that social justice rhetoric and social justice activism coalesce for all oppressed populations.
Variability in Brain Structure and Function Reflects Lack of Peer Support
Authors: Schurz Matthias , Uddin Lucina Q , Kanske Philipp , Lamm Claus , Sallet Jérôme , Bernhardt Boris C , Mars Rogier B , Bzdok Danilo
Published: April 2021

Humans are a highly social species. Complex interactions for mutual support range from helping neighbors to building social welfare institutions. During times of distress or crisis, sharing life experiences within one’s social circle is critical for well-being. By translating pattern-learning algorithms to the UK Biobank imaging-genetics cohort (n = ~40 000 participants), we have delineated manifestations of regular social support in multimodal whole-brain measurements. In structural brain variation, we identified characteristic volumetric signatures in the salience and limbic networks for high- versus low-social support individuals. In patterns derived from functional coupling, we also located interindividual differences in social support in action–perception circuits related to binding sensory cues and initiating behavioral responses. In line with our demographic profiling analysis, the uncovered neural substrates have potential implications for loneliness, substance misuse, and resilience to stress.
SARS-CoV-2 RNAemia Predicts Clinical Deterioration and Extrapulmonary Complications from COVID-19
Authors: Ram-Mohan Nikhil , Kim David , Zudock Elizabeth J , Hashemi Marjan M , Tjandra Kristel C , Rogers Angela J , Blish Catherine A , Nadeau Kari C , Newberry Jennifer A , Quinn James V , O’Hara Ruth , Ashley Euan , Nguyen Hien , Jiang Lingxia , Hung Paul , Blomkalns Andra L , Yang Samuel ,   Stanford COVID-19 Biobank Study Group, Mann Rosen , Visweswaran Anita , Ranganath Thanmayi , Roque Jonasel , Manohar Monali , Din Hena Naz , Kumar Komal , Jee Kathryn , Noon Brigit , Anderson Jill , Fay Bethany , Schreiber Donald , Zhao Nancy , Vergara Rosemary , McKechnie Julia , Wilk Aaron , de la Parte Lauren , Dantzler Kathleen Whittle , Ty Maureen , Kathale Nimish , Rustagi Arjun , Martinez-Colon Giovanny , Ivison Geoff , Pi Ruoxi , Lee Maddie , Brewer Rachel , Hollis Taylor , Baird Andrea , Ugur Michele , Bogusch Drina , Nahass George R , Haider Kazim , Tran Kim Quyen Thi , Simpson Laura , Tal Michal , Chang Iris , Do Evan , Fernandes Andrea , Lee Alexandra S , Ahuja Neera , Snow Theo , Krempski James
Published: April 2021

Background

The determinants of coronavirus disease 2019 (COVID-19) disease severity and extrapulmonary complications (EPCs) are poorly understood. We characterized relationships between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNAemia and disease severity, clinical deterioration, and specific EPCs.

Methods

We used quantitative and digital polymerase chain reaction (qPCR and dPCR) to quantify SARS-CoV-2 RNA from plasma in 191 patients presenting to the emergency department with COVID-19. We recorded patient symptoms, laboratory markers, and clinical outcomes, with a focus on oxygen requirements over time. We collected longitudinal plasma samples from a subset of patients. We characterized the role of RNAemia in predicting clinical severity and EPCs using elastic net regression.

Results

Of SARS-CoV-2–positive patients, 23.0% (44 of 191) had viral RNA detected in plasma by dPCR, compared with 1.4% (2 of 147) by qPCR. Most patients with serial measurements had undetectable RNAemia within 10 days of symptom onset, reached maximum clinical severity within 16 days, and symptom resolution within 33 days. Initially RNAemic patients were more likely to manifest severe disease (odds ratio, 6.72 [95% confidence interval, 2.45–19.79]), worsening of disease severity (2.43 [1.07–5.38]), and EPCs (2.81 [1.26–6.36]). RNA loads were correlated with maximum severity (r = 0.47 [95% confidence interval, .20–.67]).

Conclusions

dPCR is more sensitive than qPCR for the detection of SARS-CoV-2 RNAemia, which is a robust predictor of eventual COVID-19 severity and oxygen requirements, as well as EPCs. Because many COVID-19 therapies are initiated on the basis of oxygen requirements, RNAemia on presentation might serve to direct early initiation of appropriate therapies for the patients most likely to deteriorate.
Effectiveness of Influenza Vaccines in the HIVE Household Cohort Over 8 Years: Is There Evidence of Indirect Protection?
Authors: Malosh Ryan E , Petrie Joshua G , Callear Amy , Truscon Rachel , Johnson Emileigh , Evans Richard , Bazzi Latifa , Cheng Caroline , Thompson Mark S , Martin Emily T , Monto Arnold S
Published: April 2021

Background

The evidence that influenza vaccination programs regularly provide protection to unvaccinated individuals (ie, indirect effects) of a community is lacking. We sought to determine the direct, indirect, and total effects of influenza vaccine in the Household Influenza Vaccine Evaluation (HIVE) cohort.

Methods

Using longitudinal data from the HIVE cohort from 2010–11 through 2017–18, we estimated direct, indirect, and total influenza vaccine effectiveness (VE) and the incidence rate ratio of influenza virus infection using adjusted mixed-effect Poisson regression models. Total effectiveness was determined through comparison of vaccinated members of full or partially vaccinated households to unvaccinated individuals in completely unvaccinated households.

Results

The pooled, direct VE against any influenza was 30.2% (14.0–43.4). Direct VE was higher for influenza A/H1N1 43.9% (3.9 to 63.5) and B 46.7% (17.2 to 57.5) than A/H3N2 31.7% (10.5 to 47.8) and was higher for young children 42.4% (10.1 to 63.0) than adults 18.6% (−6.3 to 37.7). Influenza incidence was highest in completely unvaccinated households (10.6 per 100 person-seasons) and lower at all other levels of household vaccination coverage. We found little evidence of indirect VE after adjusting for potential confounders. Total VE was 56.4% (30.1–72.9) in low coverage, 43.2% (19.5–59.9) in moderate coverage, and 33.0% (12.1 to 49.0) in fully vaccinated households.

Conclusions

Influenza vaccines may have a benefit above and beyond the direct effect but that effect in this study was small. Although there may be exceptions, the goal of global vaccine recommendations should remain focused on provision of documented, direct protection to those vaccinated.
Cryptanalysis of Modular Exponentiation Outsourcing Protocols
Authors: Bouillaguet Charles , Martinez Florette , Vergnaud Damien
Published: April 2021

Public-key cryptographic primitives are time consuming for resource-constrained devices. A classical problem is to securely offload group exponentiations from a (comparatively) weak device—the client—to an untrusted more powerful device—the server. A delegation protocol must usually meet two security objectives: privacy—the exponent or the base should not be revealed to a passive adversary—and verifiability—a malicious server should not be able to make the client accept an invalid value as the result of the delegated computation. Most proposed protocols relies on a secret splitting of the exponent and the base, and a considerable amount of literature has been devoted to their analysis. Recently, Su et al. (Su, Q., Zhang, R. and Xue, R. (2020) Secure outsourcing algorithms for composite modular exponentiation based on single untrusted cloud. Comput. J., 63, 1271.) and Rangasamy and Kuppusamy (Rangasamy, J. and Kuppusamy, L. (2018) Revisiting Single-Server Algorithms for Outsourcing Modular Exponentiation. In Chakraborty, D. and Iwata, T. (eds), Progress in Cryptology - INDOCRYPT 2018: 19th International Conference in Cryptology in India, New Delhi, India, December 912, Vol. 11356, Lecture Notes in Computer Science. Springer, Heidelberg, Germany, pp. 320. proposed outsourcing protocols for modular exponentiations. They claim that their protocols achieve security (privacy and verifiability). We show that these claims are flawed and that their schemes are broken beyond repair. They remain insecure even if one increases significantly the proposed parameters (and consequently the protocols computational and communication complexities). Our attacks rely on standard lattice-based cryptanalytic techniques, namely the Coppersmith methods to find small integer zeroes of modular multivariate polynomials and simultaneous Diophantine approximation methods for the so-called approximate greatest common divisor problem.
Salvage radiotherapy for postoperative locoregional failure in esophageal cancer: a systematic review and meta-analysis
Authors: Mummudi N , Jiwnani S , Niyogi D , Srinivasan S , Ghosh-Laskar S , Tibdewal A , Rane P , Karimundackal G , Pramesh C S , Agarwal J P
Published: April 2021

Locoregional recurrences following surgery for esophageal cancers represent a significant clinical problem with no standard recommendations for management. We conducted this systematic review and meta-analysis with the objective of studying safety and efficacy of salvage radiotherapy in this setting. All prospective and retrospective cohort studies, which studied patients who developed locoregional recurrence following initial radical surgery for esophageal cancer and subsequently received salvage radiation therapy (RT)/chemoradiation with all relevant information regarding survival outcome and toxicity available, were included. The quality of eligible individual studies was assessed using the Newcastle-Ottawa Scale score for risk of bias. R package MetaSurv was used to obtain a summary survival curve from survival probabilities and numbers of at-risk patients collected at various time points and to test the overall heterogeneity using the I2 statistic. Thirty studies (27 retrospective, 3 prospective) published from 1995 to 2020 with 1553 patients were included. The median interval between surgery and disease recurrence was 12.5 months. The median radiation dose used was 60 Gy and 57% received concurrent chemotherapy. The overall incidence of acute grade 3/4 mucositis and dermatitis were 8 and 4%, respectively; grade 3/4 acute pneumonitis was reported in 5%. The overall median follow-up of all studies included was 27 months. The 1-, 2- and 3-year overall survival (OS) probabilities were 67.9, 35.9 and 30.6%, respectively. Factors which predicted better survival on multivariate analysis were good PS, lower group stage, node negativity at index surgery, longer disease-free interval, nodal recurrence (as compared to anastomotic site recurrence), smaller disease volume, single site of recurrence, RT dose >50 Gy, conformal RT, use of concomitant chemotherapy and good radiological response after radiotherapy. Salvage radiotherapy with or without concomitant chemotherapy for locoregional recurrences after surgery for esophageal cancer is safe and effective. Modern radiotherapy techniques may improve outcomes and reduce treatment-related morbidity.
Remote monitoring of patients with heart failure during the first national lockdown for COVID-19 in France
Authors: Ploux Sylvain , Strik Marc , Abu-Alrub Saer , Ramirez F Daniel , Buliard Samuel , Marchand Hugo , Picard François , Eschalier Romain , Haïssaguerre Michel , Bordachar Pierre
Published: April 2021

Aims

Multiparametric remote monitoring of patients with heart failure (HF) has the potential to mitigate the health risks of lockdowns for COVID-19. We aimed to compare healthcare use, physiological variables, and HF decompensations during 1 month before and during the first month of the first French national lockdown for COVID-19 among patients undergoing remote monitoring.

Methods and results

Transmitted vital parameters and data from cardiac implantable electronic devices were analysed in 51 patients. Medical contact was defined as the sum of visits and days of hospitalization. The lockdown was associated with a marked decrease in cardiology medical contact (118 days before vs. 26 days during, −77%, P = 0.003) and overall medical contact (180 days before vs. 79 days during, −58%, P = 0.005). Patient adherence with remote monitoring was 84 ± 21% before and 87 ± 19% during lockdown. The lockdown was not associated with significant changes in various parameters, including physical activity (2 ± 1 to 2 ± 1 h/day), weight (83 ± 16 to 83 ± 16 kg), systolic blood pressure (121 ± 19 to 121 ± 18 mmHg), heart rate (68 ± 10 to 67 ± 10 b.p.m.), heart rate variability (89 ± 44 to 78 ± 46 ms, P = 0.05), atrial fibrillation burden (84 ± 146 vs. 86 ± 146 h/month), or thoracic impedance (66 ± 8 to 66 ± 9 Ω). Seven cases of HF decompensations were observed before lockdown, all but one of which required hospitalization, vs. six during lockdown, all but one of which were managed remotely.

Conclusions

The lockdown restrictions caused a marked decrease in healthcare use but no significant change in the clinical status of HF patients under multiparametric remote monitoring.
Credit Misallocation During the European Financial Crisis
Authors: Schivardi Fabiano , Sette Enrico , Tabellini Guido
Published: April 2021

Using data on bank-firm relationships in Italy during the Eurozone financial crisis, we show that: (i) compared to healthy banks, under-capitalised banks cut credit to healthy but not to zombie firms and are more likely to prolong a credit relationship with a zombie; (ii) in area sectors with more low-capital banks, zombies are more likely to survive; (iii) bank under-capitalisation does not hurt the growth rate of healthy firms. We provide evidence that extending credit to the weakest firms during the recession mitigated the disruption of supply chains and adverse local demand externalities.
Public awareness of the association between human papillomavirus and oropharyngeal cancer
Authors: Verhees Femke , Demers Imke , Schouten Leo J , Lechner Matt , Speel Ernst-Jan M , Kremer Bernd
Published: April 2021

Background

Early diagnosis of human papillomavirus (HPV) associated oropharyngeal cancer (OPC) is associated with improved survival. To achieve early diagnosis, it might be beneficial to increase awareness of the link between HPV and OPC. This increase of awareness could also be an important way to increase vaccination rates. The aim of our study was to explore the current public knowledge in the Netherlands regarding the association of HPV with OPC.

Methods

An online cross-sectional survey was used and sent by the company Flycatcher Internet Research to 1539 of their panel members. Data were analyzed statistically by gender, age, educational level and the participants’ use of alcohol and tobacco.

Results

The response rate was 68% (1044 participants). Our data revealed that 30.6% of the participants had heard of HPV. There was a knowledge gap regarding HPV in males (P < 0.001), people older than 65 years (P < 0.001), people with low education level (P < 0.001) and current smokers (P < 0.001). Of the respondents who had heard of HPV, only 29.2% knew of the association between HPV and OPC. We also found that only 49.7% of the population knew of the existence of an HPV vaccine.

Conclusions

The results of this survey indicate that the public awareness of HPV and the association of HPV with OPC is lacking. Interventions to increase awareness of HPV and its association with non-cervical cancer should be considered. This might help to increase the HPV vaccine uptake both for girls and boys and earlier diagnosis of this disease leading to improved survival.
Primary care provider expectations of addiction services and patients in Spain
Authors: Andreu Magalí , Alcaraz Noelia , Gual Antoni , Segura Lidia , Barrio Pablo
Published: April 2021

Background

Primary care (PC) is crucial in the care of substance use disorder (SUD) patients. However, the relationship between PC and addiction settings is complex and collaboration issues stand out. Available evidence suggests that integration of SUD and PC services can improve physical and mental health of SUD patients and reduce health expenses.

Objective

To explore the experiences, views and attitudes of PC professionals towards the interaction between PC and SUD services.

Methods

Twenty-seven GPs took part in three focus groups. The focus group sessions were audio-taped, transcribed verbatim and analysed using reflexive thematic analysis. Recurrent themes were identified.

Results

Four main themes were devised: (1) Differences and specificities of SUD patients, (2) Interaction between providers of PC and addiction services, (3) Patient management (4) Addiction stigma. These main themes reflect the consideration that SUD patients are a specific group with specific care needs that yield specific challenges to GPs themselves. Improved training, availability of a shared medical record system, increased feedback between GP and addiction specialists and the efficiency of the circuit are to be considered the main priority for the majority of the participants.

Conclusions

An efficient and effective referral circuit, with increased feedback and shared medical records is considered key to GPs. Its implementation should keep in mind the specific features of both SUD patients and GPs
The growing repertoire of genetic tools for dissecting chlamydial pathogenesis
Authors: Banerjee Arkaprabha , Nelson David E
Published: April 2021

Multiple species of obligate intracellular bacteria in the genus Chlamydia are important veterinary and/or human pathogens. These pathogens all share similar biphasic developmental cycles and transition between intracellular vegetative reticulate bodies and infectious elementary forms, but vary substantially in their host preferences and pathogenic potential. A lack of tools for genetic engineering of these organisms has long been an impediment to the study of their biology and pathogenesis. However, the refinement of approaches developed in C. trachomatis over the last 10 years, and adaptation of some of these approaches to other Chlamydia spp. in just the last few years, has opened exciting new possibilities for studying this ubiquitous group of important pathogens.
Acetylcholine signaling genes are required for cocaine-stimulated egg laying in Caenorhabditis elegans
Authors: Emerson Soren , Hay Megan , Smith Mark , Granger Ricky , Blauch David , Snyder Nicole , El Bejjani Rachid
Published: April 2021

The toxicity and addictive liability associated with cocaine abuse are well-known. However, its mode of action is not completely understood, and effective pharmacotherapeutic interventions remain elusive. The cholinergic effects of cocaine on acetylcholine receptors, synthetic enzymes, and degradative enzymes have been the focus of relatively little empirical investigation. Due to its genetic tractability and anatomical simplicity, the egg laying circuit of the hermaphroditic nematode, Caenorhabditis elegans, is a powerful model system to precisely examine the genetic and molecular targets of cocaine in vivo. Here, we report a novel cocaine-induced behavioral phenotype in C. elegans, cocaine-stimulated egg laying. In addition, we present the results of an in vivo candidate suppression screen of synthetic enzymes, receptors, degradative enzymes, and downstream components of the intracellular signaling cascades of the main neurotransmitter systems that control C. elegans egg laying. Our results show that cocaine-stimulated egg laying is dependent on acetylcholine synthesis and synaptic release, functional nicotinic acetylcholine receptors, and the C. elegans acetylcholinesterases.
The Wild Worm Codon Adapter: a web tool for automated codon adaptation of transgenes for expression in non-Caenorhabditis nematodes
Authors: Bryant Astra S , Hallem Elissa A
Published: April 2021

Advances in genomics techniques are expanding the range of nematode species that are amenable to transgenesis. Due to divergent codon usage biases across species, codon optimization is often a critical step for the successful expression of exogenous transgenes in nematodes. Platforms for generating DNA sequences codon-optimized for the free-living model nematode Caenorhabditis elegans are broadly available. However, until now such tools did not exist for non-Caenorhabditis nematodes. We therefore developed the Wild Worm Codon Adapter, a tool for rapid transgene codon optimization for expression in non-Caenorhabditis nematodes. The app includes built-in optimization for parasitic nematodes in the Strongyloides, Nippostrongylus, and Brugia genera as well as the predatory nematode Pristionchus pacificus. The app also supports custom optimization for any species using user-provided optimization rules. In addition, the app supports automated insertion of synthetic or native introns, as well as the analysis of codon bias in transgene and native sequences. Here, we describe this web-based tool and demonstrate how it may be used to analyze genome-wide codon bias in Strongyloides species.
Read between the Lines: Diversity of Nontranslational Selection Pressures on Local Codon Usage
Authors: Callens Martijn , Pradier Léa , Finnegan Michael , Rose Caroline , Bedhomme Stéphanie
Published: April 2021

Protein coding genes can contain specific motifs within their nucleotide sequence that function as a signal for various biological pathways. The presence of such sequence motifs within a gene can have beneficial or detrimental effects on the phenotype and fitness of an organism, and this can lead to the enrichment or avoidance of this sequence motif. The degeneracy of the genetic code allows for the existence of alternative synonymous sequences that exclude or include these motifs, while keeping the encoded amino acid sequence intact. This implies that locally, there can be a selective pressure for preferentially using a codon over its synonymous alternative in order to avoid or enrich a specific sequence motif. This selective pressure could—in addition to mutation, drift and selection for translation efficiency and accuracy—contribute to shape the codon usage bias. In this review, we discuss patterns of avoidance of (or enrichment for) the various biological signals contained in specific nucleotide sequence motifs: transcription and translation initiation and termination signals, mRNA maturation signals, and antiviral immune system targets. Experimental data on the phenotypic or fitness effects of synonymous mutations in these sequence motifs confirm that they can be targets of local selection pressures on codon usage. We also formulate the hypothesis that transposable elements could have a similar impact on codon usage through their preferred integration sequences. Overall, selection on codon usage appears to be a combination of a global selection pressure imposed by the translation machinery, and a patchwork of local selection pressures related to biological signals contained in specific sequence motifs.
COVID-19, Time to Oneself, and Loneliness: Creativity as a Resource
Authors: Pauly Theresa , Chu Li , Zambrano Elizabeth , Gerstorf Denis , Hoppmann Christiane A
Published: April 2021

Objectives

Physical distancing to reduce the spread of the coronavirus disease 2019 has increased alone time, with unintended mental health ramifications including increased loneliness, which may be particularly detrimental for older adults. We investigated time-varying associations between daily time to oneself and loneliness, and the role of everyday creativity as a resource.

Method

126 adults aged 18–84 completed online questionnaires including a 10-day daily diary module, during which they self-reported alone time, everyday creativity, and loneliness. Data were analyzed using multilevel models, controlling for study day, participation date, gender, and relationship status.

Results

Greater average amounts of alone time were associated with greater loneliness, an association that was stronger in old age. In a daily context, individuals reported feeling lonelier on days when they had more time to themselves than usual. This within-person association was weaker with older age. Everyday creativity did not moderate alone time–loneliness associations. However, holding time to oneself constant, participants felt less lonely and less bothered by alone time on days when they were more creative than usual.

Discussion

Participating in creative behaviors (e.g., pursuing arts and crafts) might be linked with reduced loneliness. Intervention studies are needed to investigate whether fostering creativity could help promote mental well-being in times when people, especially older adults, are vulnerable to loneliness and associated health risks.
Psychological Connection to the Gay Community and Negative Self-Appraisals in Middle-Aged and Older Men Who Have Sex With Men: The Mediating Effects of Fitness Engagement
Authors: Brennan-Ing Mark , Haberlen Sabina , Ware Deanna , Egan James E , Brown Andre L , Meanley Steven , Palella Frank J , Bolan Robert , Cook Judith A , Okafor Chukwuemeka N , Friedman M Reuel , Plankey Michael W
Published: April 2021

Objectives

Connections to the gay community may elicit negative self-appraisals among men who have sex with men (MSM), which may be exacerbated for people with HIV (PWH). Fitness engagement may mediate self-appraisals by maintaining or improving appearance and health. We hypothesized that gay community connections would be positively related to negative self-appraisal and explored whether this association would be mediated by fitness engagement and moderated by HIV status.

Method

Data were obtained from the Multicenter AIDS Cohort Healthy Aging study (N = 1,026; PWH n = 525; people without HIV [PWOH] n = 501). Structural equation modeling (SEM) examined associations between gay community connections, negative self-appraisal (body image dissatisfaction, self-perception of aging), and fitness engagement (physical activity, motivation to be fit). Multiple-group SEM tested the moderating effects of HIV serostatus.

Results

The SEM fit the data well (root mean square error of approximation = 0.056; 90% CI: 0.046, 0.066). Connection to the gay community was inversely related to negative self-appraisals and positively related to fitness engagement. Fitness engagement mediated the association between community connections and negative self-appraisal and was inversely related to negative self-appraisals. Among PWH, the association between community connections and self-appraisal was weaker and the effect of fitness engagement on negative self-appraisal was stronger compared to PWOH.

Discussion

Connection to the gay community may be a source of resilience for aging MSM by lessening negative self-appraisals and promoting strategies that address body image dissatisfaction and self-perceptions of aging. Interventions facilitating connections to the gay community may support healthy aging in this population.
Empowering communities with health promotion labs: result from a CBPR programme in Malmö, Sweden
Authors: Avery Helen , Sjögren Forss Katarina , Rämgård Margareta
Published: April 2021

Health promotion is thus not only a participatory practice, but a practice for empowerment and social justice. The study describes findings from a community-based participatory and challenge-driven research program. that aimed to improve health through health promotion platform in an ethnically diverse low-income neighbourhood of Malmö, Sweden. Local residents together with lay health promoters living in the area were actively involved in the planning phase and decided on the structure and content of the program. Academic, public sector and commercial actors were involved, as well as NGOs and residents. Empowerment was used as a lens to analyse focus group interviews with participants (n=322) in six co-creative health-promoting labs on three occasions in the period 2017-2019. The CBPR interview guide focused on the dimensions of participation, collaboration and experience of the activities. The CBPR approach driven by community member contributed to empowerment processes within the health promotion labs: Health promotors building trust in social places for integration, Participants motivate each other by social support and Participants acting for community health in wider circle. CBPR Health promotion program should be followed up longitudielly with community participants to be able to see the processes of change and empowerment on the community level.
Xenophobia in the Time of a Pandemic: Social Media Use, Stereotypes, and Prejudice against Immigrants during the COVID-19 Crisis
Authors: Ahmed Saifuddin , Chen Vivian Hsueh Hua , Chib Arul Indrasen
Published: April 2021

This study examines the relationship between social media use, disease risk perception, social and political trust, and out-group stereotyping and prejudice during a social upheaval. Analyses of primary data collected during the COVID-19 outbreak in Singapore found that disease risk perception is positively related to stereotyping and prejudice against Chinese immigrants. Individuals who used social media for news were more likely to stereotype and express prejudice. However, those who engaged in frequent heterogenous discussions, and had more extensive social networks, were less likely to stereotype and express prejudice. Higher social and political trust was also associated with lower stereotyping and prejudice. Finally, moderation effects of network characteristics on the relationship between risk perception, social trust, and prejudice were observed.
A roadmap for cardiovascular care after release from incarceration: uses of a smartphone application
Authors: Surkan Pamela J , Puglisi Lisa B , Butler Karim , Elmi Nika , Zachary Wayne W
Published: April 2021

Objective

Cardiovascular disease (CVD) and its risk factors disproportionately affect people returning from incarceration. These individuals face multiple barriers to obtaining care, which can impact CVD and risk factor management and may be mitigated through use of a smartphone application (app). Therefore, we explored the CVD-related needs of people released from incarceration and which app features would support these needs.

Materials and Methods

In 2019, we collected qualitative data through 7 focus groups with 76 returning citizens and 19 key informants through interviews and small group discussions in Baltimore, Maryland. Verbal data were audio-recorded, transcribed, and analyzed using inductive thematic coding with N-Vivo qualitative software.

Results

Returning citizens face multiple barriers when trying to engage in care and services related to cardiovascular health, including around medications and health insurance. Some major challenges were identifying trusted social services and making cardiovascular health a priority. Findings suggested that CVD risk factors could be more effectively addressed in combination with attending to other pressing needs related to employment, housing, behavioral health, and building trust. Participants suggested that a smartphone app would be most useful if it broadly addressed these issues by linking returning citizens to social services, including recommendations from peers, and facilitating access to healthcare.

Discussion

Returning citizens need broad support for societal reintegration. Addressing social issues would allow them to focus on cardiovascular health.

Conclusion

Given the challenges experienced after release from incarceration, an app focused on social and health-access issues may help returning citizens meet their CVD needs.
Hypericin-mediated photodynamic therapy enhances gemcitabine induced Capan-2 cell apoptosis via inhibiting NADPH level
Authors: Sun Liyun , Shang Huoli , Wu Yuzhen , Xin Xiujuan
Published: April 2021

Objectives

The combination of gemcitabine (Gem) and hypericin (HY) enhances the apoptosis of Capan-2 cells, providing a promising option for the treatment of pancreatic cancer. Our study further explored the cytotoxic mechanism of HY combined with chemotherapy drugs on pancreatic cancer.

Methods

The proliferation rate of the cells assayed with the MTT method. The ROS (reactive oxygen species) levels of each treatment were evaluated by DCFH-DA oxidisation methods. The activity of glutathione reductase and the levels of reduced glutathione (GSH) and oxidised glutathione (GSSG) were assessed using assay kits. The expression levels of apoptosis-related proteins were analysed by western blotting.

Key findings

The activity of glucose-6-phosphate dehydrogenase (G6PDH), a key enzyme of the pentose phosphate pathway, significantly decreased in Gem + HY groups, however, the ROS level enhanced accompanying with GSH depleting, mitochondrial membrane depolarisation and cytochrome C release. Gem + HY inhibits the expression of Bcl-2 but stimulates Bax level, triggering caspase activation and PARP cleavage and thus promoted apoptosis of Capan-2 cells.

Conclusions

We demonstrated that Gem combined HY-PDT could inhibit the proliferation of Capan-2 cells and induce cell apoptosis. HY-PDT combined with Gem had a great potential on pancreatic cancer treatment clinically.
A model for phenotyping crop fractional vegetation cover using imagery from unmanned aerial vehicles
Authors: Wan Liang , Zhu Jiangpeng , Du Xiaoyue , Zhang Jiafei , Han Xiongzhe , Zhou Weijun , Li Xiaopeng , Liu Jianli , Liang Fei , He Yong , Cen Haiyan
Published: April 2021

Fractional vegetation cover (FVC) is the key trait of interest for characterizing crop growth status in crop breeding and precision management. Accurate quantification of FVC among different breeding lines, cultivars, and growth environments is challenging, especially because of the large spatiotemporal variability in complex field conditions. This study presents an ensemble modeling strategy for phenotyping crop FVC from unmanned aerial vehicle (UAV)-based multispectral images by coupling the PROSAIL model with a gap probability model (PROSAIL-GP). Seven field experiments for four main crops were conducted, and canopy images were acquired using a UAV platform equipped with RGB and multispectral cameras. The PROSAIL-GP model successfully retrieved FVC in oilseed rape (Brassica napus L.) with coefficient of determination, root mean square error (RMSE), and relative RMSE (rRMSE) of 0.79, 0.09, and 18%, respectively. The robustness of the proposed method was further examined in rice (Oryza sativa L.), wheat (Triticum aestivum L.), and cotton (Gossypium hirsutum L.), and a high accuracy of FVC retrieval was obtained, with rRMSEs of 12%, 6%, and 6%, respectively. Our findings suggest that the proposed method can efficiently retrieve crop FVC from UAV images at a high spatiotemporal domain, which should be a promising tool for precision crop breeding.
Combating the “Peacetime Effect” in Military Plastic Surgery: Implications for Mission Readiness
Authors: Fox Justin P , Markov Nickolay P , Latham Kerry P
Published: April 2021

Military treatment facility-assigned surgeons face numerous challenges in maintaining critical wartime skills, including the “peacetime effect” and the “dual mission.” Using the field of plastic surgery to illustrate these issues, we contrast plastic surgeons’ contributions to combat casualty care with primary data describing plastic surgeons’ clinical practice in many military hospitals. Then, we outline the current administrative mechanisms being promoted at the enterprise-level for surgeons to gain a more mission-focused, clinical practice, while also examining significant shortcomings in these policies. Finally, we conclude with a call to action for the military surgical community to accelerate change in the development of more robust clinical practices for our surgeons, or potentially lose our ability to field a ready surgical force.
Brassica rapa Domestication: Untangling Wild and Feral Forms and Convergence of Crop Morphotypes
Authors: McAlvay Alex C , Ragsdale Aaron P , Mabry Makenzie E , Qi Xinshuai , Bird Kevin A , Velasco Pablo , An Hong , Pires J Chris , Emshwiller Eve
Published: April 2021

The study of domestication contributes to our knowledge of evolution and crop genetic resources. Human selection has shaped wild Brassica rapa into diverse turnip, leafy, and oilseed crops. Despite its worldwide economic importance and potential as a model for understanding diversification under domestication, insights into the number of domestication events and initial crop(s) domesticated in B. rapa have been limited due to a lack of clarity about the wild or feral status of conspecific noncrop relatives. To address this gap and reconstruct the domestication history of B. rapa, we analyzed 68,468 genotyping-by-sequencing-derived single nucleotide polymorphisms for 416 samples in the largest diversity panel of domesticated and weedy B. rapa to date. To further understand the center of origin, we modeled the potential range of wild B. rapa during the mid-Holocene. Our analyses of genetic diversity across B. rapa morphotypes suggest that noncrop samples from the Caucasus, Siberia, and Italy may be truly wild, whereas those occurring in the Americas and much of Europe are feral. Clustering, tree-based analyses, and parameterized demographic inference further indicate that turnips were likely the first crop type domesticated, from which leafy types in East Asia and Europe were selected from distinct lineages. These findings clarify the domestication history and nature of wild crop genetic resources for B. rapa, which provides the first step toward investigating cases of possible parallel selection, the domestication and feralization syndrome, and novel germplasm for Brassica crop improvement.
Lysophosphatidic acid improves oocyte quality during IVM by activating the ERK1/2 pathway in cumulus cells and oocytes
Authors: Ma Yerong , Yang Weijie , Ren Peipei , Li Xiang , Jin Jiamin , Dai Yongdong , Pan Yibin , Jiang Lingling , Fan Hengyu , Zhang Yinli , Zhang Songying
Published: April 2021

Oocyte IVM technology is an option for fertility preservation in some groups of patients, such as those with polycystic ovary syndrome, patients with ovarian hyperstimulation syndrome, and for patients with cancer. However, the developmental potential of oocytes from IVM still needs to improve. Several previous studies have reported that lysophosphatidic acid (LPA) promotes glucose metabolism, cumulus cell (CC) expansion, and oocyte nuclear maturation. However, the effect of LPA on oocyte cytoplasmic maturation, particularly mitochondrial function, has rarely been studied and the underlying mechanism is largely unknown, which impedes (pre)clinical applications of LPA. In this study, cumulus-oocyte complexes (COCs) and cumulus-denuded germinal vesicle oocytes (DOs) were treated with various concentrations of LPA during IVM, in the presence or absence of the oxidative stressor cyclophosphamide (CTX). In both normal and CTX-damaged COCs, the 25 μM LPA group exhibited improved CC expansion capacity, a higher nuclear maturation rate, and superior mitochondrial function, compared to no LPA treatment. When the concentration of LPA was over 40 μM, detrimental effects of LPA on oocyte maturation occurred. Compared with COCs, the addition of LPA slightly improved oocyte nuclear and cytoplasmic maturation of DOs, but this was not statistically significant. We observed that LPA promotes the activation of extracellular signal-regulated kinase (ERK)1/2, although this was not statistically significant in DOs. Furthermore, LPA could not reverse the negative effect of CC expansion and mitochondrial function after inactivation of ERK1/2 by U0126. RNA-sequencing and RT-PCR results showed that LPA upregulated several ERK1/2 downstream genes related to CC expansion, such as Areg, Cited4, and Ptgs2. This study demonstrates that LPA improves oocyte quality during IVM through the activation of ERK1/2 pathway CCs and oocytes, which provides evidence for the potential addition of LPA to IVM medium.
Rcl1 depletion impairs 18S pre-rRNA processing at the A1-site and up-regulates a cohort of ribosome biogenesis genes in zebrafish
Authors: Zhu Qinfang , Tao Boxiang , Chen Hong , Shi Hui , Huang Ling , Chen Jun , Hu Minjie , Lo Li Jan , Peng Jinrong
Published: April 2021

Yeast Rcl1 is a potential endonuclease that mediates pre-RNA cleavage at the A2-site to separate 18S rRNA from 5.8S and 25S rRNAs. However, the biological function of Rcl1 in opisthokonta is poorly defined. Moreover, there is no information regarding the exact positions of 18S pre-rRNA processing in zebrafish. Here, we report that zebrafish pre-rRNA harbours three major cleavage sites in the 5′ETS, namely –477nt (A′-site), –97nt (A0-site) and the 5′ETS and 18S rRNA link (A1-site), as well as two major cleavage regions within the ITS1, namely 208–218nt (site 2) and 20–33nt (site E). We also demonstrate that depletion of zebrafish Rcl1 mainly impairs cleavage at the A1-site. Phenotypically, rcl1–/– mutants exhibit a small liver and exocrine pancreas and die before 15 days post-fertilization. RNA-seq analysis revealed that the most significant event in rcl1–/– mutants is the up-regulated expression of a cohort of genes related to ribosome biogenesis and tRNA production. Our data demonstrate that Rcl1 is essential for 18S rRNA maturation at the A1-site and for digestive organogenesis in zebrafish. Rcl1 deficiency, similar to deficiencies in other ribosome biogenesis factors, might trigger a common mechanism to upregulate the expression of genes responsible for ribosome biogenesis.
TbTRF suppresses the TERRA level and regulates the cell cycle-dependent TERRA foci number with a TERRA binding activity in its C-terminal Myb domain
Authors: Saha Arpita , Gaurav Amit Kumar , Pandya Unnati M , Afrin Marjia , Sandhu Ranjodh , Nanavaty Vishal , Schnur Brittny , Li Bibo
Published: April 2021

Telomere repeat-containing RNA (TERRA) has been identified in multiple organisms including Trypanosoma brucei, a protozoan parasite that causes human African trypanosomiasis. T. brucei regularly switches its major surface antigen, VSG, to evade the host immune response. VSG is expressed exclusively from subtelomeric expression sites, and we have shown that telomere proteins play important roles in the regulation of VSG silencing and switching. In this study, we identify several unique features of TERRA and telomere biology in T. brucei. First, the number of TERRA foci is cell cycle-regulated and influenced by TbTRF, the duplex telomere DNA binding factor in T. brucei. Second, TERRA is transcribed by RNA polymerase I mainly from a single telomere downstream of the active VSG. Third, TbTRF binds TERRA through its C-terminal Myb domain, which also has the duplex DNA binding activity, in a sequence-specific manner and suppresses the TERRA level without affecting its half-life. Finally, levels of the telomeric R-loop and telomere DNA damage were increased upon TbTRF depletion. Overexpression of an ectopic allele of RNase H1 that resolves the R-loop structure in TbTRF RNAi cells can partially suppress these phenotypes, revealing an underlying mechanism of how TbTRF helps maintain telomere integrity.