bluuebunny/crossref_metadata_2025 huggingface dataset:
Long non-coding RNA Gm37494 alleviates osteoarthritis chondrocyte injury via the microRNA-181a-5p/GABRA1 axis
Authors: Yuan Aidong , Wu Penghuan , Zhong Zhinian , He Zhengyan , Li Wenhu
Published: June 2022

Objective

This study was conducted to investigate the effect of long non-coding RNA (lncRNA) Gm37494 on osteoarthritis (OA) and its related molecular mechanism.

Methods

The cartilage tissues were obtained from OA patients, and an OA mouse model was induced by the destabilization of the medial meniscus, followed by measurement of Gm37494, microRNA (miR)-181a-5p, GABRA1 mRNA, and the encoded GABAARα1 protein expression. Thereafter, a cellular model was induced by interleukin-1β (IL-1β) treatment in chondrocytes, followed by ectopic and silencing experiments. Chondrocyte proliferation was detected by CCK-8 and EdU assays, chondrocyte apoptosis by flow cytometry and western blot, and the levels of inflammatory factors by ELISA. The binding of Gm37494 to miR-181a-5p was evaluated by dual-luciferase reporter gene and RIP assays, and that of GABRA1 to miR-181a-5p by dual-luciferase reporter gene and RNA pull-down assays.

Results

OA patients and mice had decreased GABRA1 mRNA and GABAARα1 protein levels and elevated miR-181a-5p expression in cartilage tissues. Additionally, Gm37494 was poorly expressed in OA mice. Mechanistically, Gm37494 directly bound to and inversely modulated miR-181a-5p that negatively targeted GABRA1. In IL-1β-induced chondrocytes, Gm37494 overexpression enhanced cell proliferation and suppressed cell apoptosis and inflammation, whereas further miR-181a-5p up-regulation or GABRA1 silencing abolished these trends.

Conclusions

Conclusively, Gm37494 elevated GABRA1 expression by binding to miR-181a-5p, thus ameliorating OA-induced chondrocyte damage.
Adolescents’ mental health and maladaptive behaviors before the Covid-19 pandemic and 1-year after: analysis of trajectories over time and associated factors
Authors: Pedrini Laura , Meloni Serena , Lanfredi Mariangela , Ferrari Clarissa , Geviti Andrea , Cattaneo Annamaria , Rossi Roberta
Published: June 2022

Background

Adolescents have been deeply exposed to negative consequences of social distancing imposed by Covid-19. There is a lack of longitudinal studies regarding the impact on adolescents of this unfavorable condition, and their results are controversial. The aim of the present prospective study is to assess psychopathological symptoms in adolescent students over time and to evaluate what type of impact the Covid-19 pandemic had on adolescents. Moreover, the association between mental health indexes, potential risk and resilience factors is explored.

Methods

Psychopathological symptoms (i.e., anxiety, depression, stress, emotional dysregulation, maladaptive behaviours), and potential risk and resilience factors (i.e., childhood trauma, emotional regulation skills, family function, personality traits) were assessed among a sample of 153 students (72% female; mean age 16.1 ± 0.49), living in a medium-size city in the north of Italy, at two time points: before the outbreak of the Covid-19 pandemic (November 2019–January 2020) and 1 year later (April–May 2021).

Results

After 1 year, we found an increase in mean scores on anxiety, stress for future uncertainty, and higher frequency of maladaptive behaviours. By contrast, the level of stress related to social domains (i.e., school attendance, romantic relationships, peer pressure) decreased. Dysfunctional emotional regulation skills, childhood trauma, low family functioning, and specific personality traits were associated to higher psychopathological symptoms. Cluster analysis detected three groups of youths based on their change over time in psychopathological symptoms: those who worsened (N = 23; 15%), improved (N = 55; 34%), or remained stable (N = 75; 46%). After controlling for baseline mental health status, those adolescents reporting increase in self-harm (OR = 2.61; p < 0.001), binge-drinking (OR = 3.0; p = 0.007), aggressiveness (OR 1.92; p = 0.004), and binge-eating (OR 2.55; p = 0.003) were more likely to present a worsened mental health condition.

Conclusion

The present results suggest that the Covid-19 pandemic seems to have had a different impact on subgroups of students. Indeed, we found a global worsening of psychological well-being only in a subgroup of adolescents, otherwise other students remained stable or improved. Increased frequency of maladaptive behaviors was found as a predictor of worsened mental health, therefore interventions to strengthen emotional regulation strategies are warranted. Finally, the decrease of stress in social domains could be due to reduction of potential triggering situations, thus indicating only a temporary beneficial effect that requires careful monitoring.
Literacy-adapted, electronic family history assessment for genetics referral in primary care: patient user insights from qualitative interviews
Authors: Mittendorf Kathleen F. , Lewis Hannah S. , Duenas Devan M. , Eubanks Donna J. , Gilmore Marian J. , Goddard Katrina A. B. , Joseph Galen , Kauffman Tia L. , Kraft Stephanie A. , Lindberg Nangel M. , Reyes Ana A. , Shuster Elizabeth , Syngal Sapna , Ukaegbu Chinedu , Zepp Jamilyn M. , Wilfond Benjamin S. , Porter Kathryn M.
Published: June 2022

Background

Risk assessment for hereditary cancer syndromes is recommended in primary care, but family history is rarely collected in enough detail to facilitate risk assessment and referral – a roadblock that disproportionately impacts individuals with healthcare access barriers. We sought to qualitatively assess a literacy-adapted, electronic patient-facing family history tool developed for use in diverse, underserved patient populations recruited in the Cancer Health Assessments Reaching Many (CHARM) Study.

Methods

Interview participants were recruited from a subpopulation of CHARM participants who experienced barriers to tool use in terms of spending a longer time to complete the tool, having incomplete attempts, and/or providing inaccurate family history in comparison to a genetic counselor-collected standard. We conducted semi-structured interviews with participants about barriers and facilitators to tool use and overall tool acceptability; interviews were recorded and professionally transcribed. Transcripts were coded based on a codebook developed using inductive techniques, and coded excerpts were reviewed to identify overarching themes related to barriers and facilitators to family history self-assessment and acceptability of the study tool.

Results

Interviewees endorsed the tool as easy to navigate and understand. However, they described barriers related to family history information, literacy and language, and certain tool functions. Participants offered concrete, easy-to-implement solutions to each barrier. Despite experience barriers to use of the tool, most participants indicated that electronic family history self-assessment was acceptable or preferable in comparison to clinician-collected family history.

Conclusions

Even for participants who experienced barriers to tool use, family history self-assessment was considered an acceptable alternative to clinician-collected family history. Barriers experienced could be overcome with minor adaptations to the current family history tool.

Trial registration

This study is a sub-study of the Cancer Health Assessments Reaching Many (CHARM) trial, ClinicalTrials.gov, NCT03426878. Registered 8 February 2018.
Unincreased risk of hospitalized infection under targeted therapies versus methotrexate in elderly patients with rheumatoid arthritis: a retrospective cohort study
Authors: Sakai Ryoko , Tanaka Eiichi , Majima Masako , Harigai Masayoshi
Published: June 2022

Background

Infection is one of the primary concerns during treatment for rheumatoid arthritis (RA) in elderly patients. However, infection risk of patients with RA receiving targeted therapy (TT) including biological disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitors (JAKIs) in elderly patients are scarce. The aim of this study was to compare the risk of hospitalized infection (HI) with TT versus methotrexate (MTX) therapy among young, elderly, and older elderly patients with RA.

Methods

Using Japanese claims data, patients satisfying the following criteria were enrolled: (1) ≥ one ICD10 code for RA; (2) ≥ one prescription of MTX or TT (bDMARDs and JAKIs) between April 2008 and September 2018; and (3) ≥16 years old. We calculated the incidence rate (IR) of HI per 100 patient-years in the young, elderly, and older elderly groups (those aged 16–64, 65–74, and ≥75 years, respectively) and the IR ratio (TT vs. MTX) of HI. A logistic regression model was used to estimate the associations between HI and TT versus MTX in each group.

Results

The overall IR of HI per 100 patient-years (95% confidence interval) was 3.2 [2.9–3.5], 5.0 [4.6–5.4], and 10.1 [9.5–10.9] in the young, elderly, and older elderly groups, respectively. Concomitant use of MTX or immunosuppressive DMARDs with TT was less frequent in the elderly and older elderly groups. The adjusted odds ratio of TT vs. MTX for HI was 1.3 (1.0–1.7;p= 0.021), 0.79 (0.61–1.0;p= 0.084), and 0.73 (0.56–0.94;p= 0.015) in the young, elderly, and older elderly groups, respectively.

Conclusion

The overall IR of HI was increased with age. The risk of HI under TT compared to MTX was not elevated in elderly and older elderly patients after adjusting for patients’ characteristics and concomitant treatments.
Efficacy and safety of HLX01 in patients with moderate-to-severe rheumatoid arthritis despite methotrexate therapy: a phase 3 study
Authors: Zeng Xiaofeng , Liu Ju , Liu Xiumei , Wu Lijun , Liu Yi , Liao Xiangping , Liu Huaxiang , Hu Jiankang , Lu Xin , Chen Linjie , Xu Jian , Jiang Zhenyu , Lu Fu-ai , Wu Huaxiang , Li Ying , Wang Qingyu , Zhu Jun ,   the HLX01-RA03 Investigators, Sun Lingyun , Wang Meimei , Yu Xiaoxia , Yang Pingting , Zou Qinghua , Xu Baijie , Zhang Hua , Huang Cibo , Bi Liqi , Li Xiaoxia , Cheng Jianzhao , Wei Hua , He Lan , Zhang Hao , Sun Hongsheng , Shuai Zongwen , Zhao Jianhong , Li Yang , Li Rongbin , Li Fengju , Li Xiaomei , Zhang Zhuoli , Qi Wufang , Du Hongwei , Jin Jingchun , Wu Jian
Published: June 2022

Background

To evaluate the efficacy and safety of HLX01, a rituximab biosimilar, as combination therapy with methotrexate in Chinese patients with active rheumatoid arthritis who had inadequate responses to methotrexate.

Methods

In this double-blind, placebo-controlled phase 3 trial, biologic-naïve patients with moderate-to-severe active rheumatoid arthritis and inadequate responses to methotrexate were randomized 2:1 to receive 1000 mg HLX01 or placebo intravenously on days 1 and 15. On the first day of weeks 24 and 26, patients in both groups received 1000 mg HLX01 via intravenous infusion. The primary endpoint was the American College of Rheumatology (ACR) 20 response rate at week 24. Secondary endpoints including efficacy, safety, immunogenicity, pharmacokinetics and pharmacodynamics were assessed up to week 48.

Results

Between 28 May 2018 and 11 September 2020, 275 patients were randomized to the HLX01 group (n = 183) or the placebo group (n = 92). At week 24, the proportion of patients achieving ACR20 response was significantly greater in the HLX01 group compared with the placebo group in the intention-to-treat population (60.7% vs 35.9%; P < 0.001) and per-protocol set (60.3% vs 37.1%; P < 0.001). Most secondary efficacy endpoints favoured HLX01 when assessed at weeks 12, 24, 36 and 48. Incidences of treatment-emergent adverse events were similar between groups. Infusion-related reactions occurred more frequently following the initial two doses of HLX01 than the subsequent doses.

Conclusions

HLX01 plus methotrexate improved clinical outcomes compared with placebo in Chinese patients with rheumatoid arthritis who had inadequate responses to methotrexate. This treatment regimen was well tolerated, showing comparable safety profiles to placebo.

Trial registration

ClinicalTrials.gov, NCT03522415. Registered on 11 May 2018.
The Myotube Analyzer: how to assess myogenic features in muscle stem cells
Authors: Noë Simon , Corvelyn Marlies , Willems Sarah , Costamagna Domiziana , Aerts Jean-Marie , Van Campenhout Anja , Desloovere Kaat
Published: June 2022

Background

The analysis of in vitro cultures of human adult muscle stem cells obtained from biopsies delineates the potential of skeletal muscles and may help to understand altered muscle morphology in patients. In these analyses, the fusion index is a commonly used quantitative metric to assess the myogenic potency of the muscle stem cells. Since the fusion index only partly describes myogenic potency, we developed the Myotube Analyzer tool, which combines the definition of the fusion index with extra features of myonuclei and myotubes obtained from satellite cell cultures.

Results

The software contains image adjustment and mask editing functions for preprocessing and semi-automatic segmentation, while other functions can be used to determine the features of nuclei and myotubes. The fusion index and a set of five novel parameters were tested for reliability and validity in a comparison between satellite cell cultures from children with cerebral palsy and typically developing children. These novel parameters quantified extra nucleus and myotube properties and can be used to describe nucleus clustering and myotube shape. Two analyzers who were trained in cell culture defined all parameters using the Myotube Analyzer app. Out of the six parameters, five had good reliability reflected by good intra-class correlation coefficients (> 0.75). Children with cerebral palsy were significantly different from the typically developing children (p < 0.05) for five parameters, and for three of the six parameters, these differences exceeded the minimal detectable differences.

Conclusions

The Myotube Analyzer can be used for the analysis of fixed differentiated myoblast cultures with nuclear and MyHC staining. The app can calculate the fusion index, an already existing parameter, but also provides multiple new parameters to comprehensively describe myogenic potential in its output. The raw data used to determine these parameters are also available in the output. The parameters calculated by the tool can be used to detect differences between cultures from children with cerebral palsy and typically developing children. Since the program is open source, users can customize it to fit their own analysis requirements.
Using decision-analysis modelling to estimate the economic impact of the identification of unrecognised bipolar disorder in primary care: the untapped potential of screening
Authors: Benacek Jiri , Martin-Key Nayra A. , Spadaro Benedetta , Tomasik Jakub , Bahn Sabine
Published: June 2022

Background

Patients with bipolar disorder are often unrecognised and misdiagnosed with major depressive disorder leading to higher direct costs and pressure on the medical system. Novel screening tools may mitigate the problem. This study was aimed at investigating the direct costs of bipolar disorder misdiagnosis in the general population, evaluating the impact of a novel bipolar disorder screening algorithm, and comparing it to the established Mood Disorder Questionnaire. A decision analysis model was built to quantify the utility of one-time screening for bipolar disorder in primary care adults presenting with a depressive episode. A hypothetical population of interest comprised a healthcare system of one million users, corresponding to 15,000 help-seekers diagnosed with major depressive disorder annually, followed for five years. The model was used to calculate the impact of screening for bipolar disorder, compared to no screening, in terms of accuracy and total direct costs to a third-party payer at varying diagnostic cut-offs. Decision curve analysis was used to evaluate clinical utility.

Results

Compared to no screening, one-time screening for bipolar disorder using the algorithm reduced the number of misdiagnoses from 680 to 260, and overall direct costs from $50,936 to $49,513 per patient, accounting for $21.3 million savings over the five-year period. The algorithm outperformed the Mood Disorder Questionnaire, which yielded 367 misdiagnoses and $18.3 million savings over the same time. Decision curve analysis showed the screening model was beneficial.

Conclusions

Utilisation of bipolar disorder screening strategies could lead to a substantial reduction in human suffering by reducing misdiagnosis, and also lessen the healthcare costs.
Trends in western USA fire fuels using historical data and modeling
Authors: Boisramé Gabrielle F. S. , Brown Timothy J. , Bachelet Dominique M.
Published: June 2022

Background

Recent increases in wildfire activity in the Western USA are commonly attributed to a confluence of factors including climate change, human activity, and the accumulation of fuels due to fire suppression. However, a shortage of long-term forestry measurements makes it difficult to quantify regional changes in fuel loads over the past century. A better understanding of fuel accumulation is vital for managing forests to increase wildfire resistance and resilience. Numerical models provide one means of estimating changes in fuel loads, but validating these models over long timescales and large geographic extents is made difficult by the scarcity of sufficient data. One such model, MC2, provides estimates of multiple types of fuel loads and simulates fire activity according to fuel and climate conditions. We used the Forest Inventory and Analysis Database (FIADB) observed data to validate MC2 estimates of fuel load change over time where possible.

Results

We found that the MC2 model’s accuracy varied geographically, but at a regional scale the distributions of changes in fuel loads were similar to distributions of FIADB values. While FIADB data provided consistent measurement types across a wide geographic area, usable data only spanned approximately 30 years. We therefore supplemented this quantitative validation with a qualitative comparison to data that covered less area, but for much longer time spans: long-term forestry plots outside of the FIA plot network and repeat photography studies. Both model results and long-term studies show increases in fuel loads over the past century across much of the western USA, with exceptions in the Pacific Northwest and other areas. Model results also suggest that not all of the increases are due to fire suppression.

Conclusions

This model validation and aggregation of information from long-term studies not only demonstrate that there have been extensive fuel increases in the western USA but also provide insights into the level of uncertainty regarding fire suppression’s impact on fuel loads. A fuller understanding of changing fuel loads and their impact on fire behavior will require an increase in the number of long-term observational forestry studies.
Dielectric properties of porous rocks with partially saturated fractures from finite-difference modeling
Authors: Bao Hongshuai , Han Tongcheng , Fu Li-Yun
Published: June 2022

Fractures are common features of geologic rocks, and they have a profound influence on the fluid flow and transport characteristics as well as physical properties of the fracture-bearing rocks. Fractures are frequently partially saturated in hydrocarbon reservoirs, and the dielectric properties that are highly sensitive to the fluid types and concentrations are useful tools for the quantitative characterization of reservoir rocks with partially saturated fractures. However, the effects of partially saturated fractures on the dielectric properties of the porous rock are still poorly understood. Based on a 3D finite-difference model, we have bridged this knowledge gap by studying the frequency-dependent dielectric properties of a porous carbonate rock with partially saturated fractures obtained by the brine-displacing oil simulation. We find that the conductivity and high-frequency (higher than approximately 1 MHz) relative permittivity generally increase, whereas the low-frequency relative permittivity and peak dielectric loss decrease with the increasing brine saturation. We also find that the partially saturated fractured rock with lower brine saturation exhibits a greater low-frequency relative permittivity and maximum dielectric loss factor than the cases in which the fractures are completely filled with oil. A systematic investigation based on simplified intersecting fracture models suggests that the oil-brine distribution is the main reason for the abnormal dielectric responses of the low-frequency relative permittivity and the maximum dielectric loss factor at low brine saturations. The results provide new insights for the comprehensive understanding of the frequency-dependent dielectric responses of fractured sedimentary rocks and will pave the way for the quantification of the brine saturation in partially saturated fractures.
Maternal Lipid Metabolism Is Associated With Neonatal Adiposity: A Longitudinal Study
Authors: Rojas-Rodriguez Raziel , Price Lori Lyn , Somogie Jessica , Hauguel-de Mouzon Sylvie , Kalhan Satish C , Catalano Patrick M
Published: June 2022

Context

Pregnancy is characterized by progressive decreases in glucose insulin sensitivity. Low insulin sensitivity resulting in hyperglycemia is associated with higher neonatal adiposity. However, less is known regarding lipid metabolism, particularly lipid insulin sensitivity in pregnancy and neonatal adiposity.

Objective

Because higher maternal prepregnancy body mass index is strongly associated with both hyperlipidemia and neonatal adiposity, we aimed to examine the longitudinal changes in basal and clamp maternal lipid metabolism as contributors to neonatal adiposity.

Methods

Twelve women planning a pregnancy were evaluated before pregnancy, in early (12-14 weeks), and late (34-36 weeks) gestation. Body composition was estimated using hydrodensitometry. Basal and hyperinsulinemic-euglycemic clamp glucose and glycerol turnover (GLYTO) were measured using 2H2-glucose and 2H5-glycerol and substrate oxidative/nonoxidative metabolism with indirect calorimetry. Total body electrical conductivity was used to estimate neonatal body composition.

Results

Basal free-fatty acids decreased with advancing gestation (P = 0.0210); however, basal GLYTO and nonoxidative lipid metabolism increased over time (P = 0.0046 and P = 0.0052, respectively). Further, clamp GLYTO and lipid oxidation increased longitudinally over time (P = 0.0004 and P = 0.0238, respectively). There was a median 50% increase and significant positive correlation during both basal and clamp GLYTO from prepregnancy through late gestation. Neonatal adiposity correlated with late pregnancy basal and clamp GLYTO (r = 0.6515, P = 0.0217; and r = 0.6051, P = 0.0371).

Conclusions

Maternal prepregnancy and late pregnancy measures of basal and clamp lipid metabolism are highly correlated. Late pregnancy basal and clamp GLYTO are significantly associated with neonatal adiposity and account for ~40% of the variance in neonatal adiposity. These data emphasize the importance of maternal lipid metabolism relating to fetal fat accrual.
Irish Postcolonial Studies, 1980–2021
Authors: Cleary Joe
Published: June 2022

This essay contests the idea that Irish postcolonial studies is a diminished field in contemporary Ireland, instead contending that it has been a sustained and significant critical force in Irish studies for over four decades and will likely remain so. The Irish “decade of centenaries,” international protests against institutional racism, and “decolonizing the university” controversies have brought issues of colonialism, racism, and empire to new prominence in Irish society and encouraged the take-up of postcolonial critique in Irish historiography, political studies, and other disciplines. The essay surveys the achievements and limitations of Irish postcolonial studies, primarily in the field of cultural analysis, since the 1980s and concludes with an assessment of major challenges ahead. The crises of contemporary global capitalism, it suggests, will impel postcolonial studies not just to engage received histories of empire and anti-imperial struggle but also to consider current conjunctures in terms of postcapitalist futures.
Ireland’s Commodity Frontiers
Authors: Smith Cathal
Published: June 2022

Commodity frontiers are transnational zones of ecological exploitation that have provided agricultural products and raw materials for international markets since the early modern era. As such, commodity frontiers have played a crucial role in the expansion and development of global capitalism by supplying items including cereals, meat, cotton, sugar, coal, iron, and oil. This article argues that rural Ireland was part of capitalism’s commodity frontiers from the sixteenth century and demonstrates how changing patterns of Irish livestock and grain production—as well as related local and national socioeconomic changes—were tied to global trends and influences. This article also suggests that the case study of the history of Irish agriculture within the context of the world economy’s commodity frontiers contributes to the debates surrounding the historiographical movement associated with the new history of capitalism.
“He is a Morfidite and Needs a Man”
Authors: Raheja Michelle
Published: June 2022

This essay focuses on queer Indigenous life in the early twentieth century through an analysis of the archive of Nabor Feliz, an Indigenous sculptor who toured with major circuses. In the essay, the author employs queer critique and Indigenous theory to contend that the circus offered Feliz opportunities for Indigenous expressions of sexuality that might not have been otherwise afforded them in this period. The essay is based on an examination of the photographs, letters, and newspaper articles in the archive, which is housed at the Southwest Museum. To the author's knowledge, this is the first article-length piece on the complexities of queer Indigenous life in the first half of the twentieth century and the first study of Feliz's life and work.
Factors affecting gestation periods in elasmobranch fishes
Authors: Tokunaga Soma , Watanabe Yuuki Y. , Kawano Mai , Kawabata Yuuki
Published: June 2022

Gestation periods vary greatly across elasmobranch species. Differences in body size and body temperature (i.e. major determinants of metabolic rates) might explain such variation. Although temperature effects have been demonstrated for captive animals, body size effects remain undocumented. Moreover, whether metabolic rates of mothers or those of embryos affect gestation periods remains unclear. Because biological times generally scale with mass1−β, where β is metabolic scaling exponent (0.8–0.9 in fishes), we hypothesized that elasmobranch gestation periods would scale with mass0.1–0.2. We also hypothesized that regionally endothermic species with elevated metabolic rates should have shorter gestation periods than similar-sized ectothermic species if the metabolic rates of mothers are responsible. We compiled data on gestation periods for 36 elasmobranch species to show that gestation periods scale with M0.11 and m0.17, where M and m are adult female mass and birth mass, respectively. Litter size and body temperature also affected gestation periods. Our findings suggest that the body-mass dependence of metabolic rate explains some variations in elasmobranch gestation periods. Unexpectedly, regionally endothermic sharks did not have shorter gestation periods than their ectothermic counterparts, suggesting that the metabolic rates of embryos, which are likely ectothermic in all elasmobranch species, may be responsible.

This article has an associated First Person interview with the first author of the paper.
Enhancer-gene specificity in development and disease
Authors: Pachano Tomás , Haro Endika , Rada-Iglesias Alvaro
Published: June 2022

Enhancers control the establishment of spatiotemporal gene expression patterns throughout development. Over the past decade, the development of new technologies has improved our capacity to link enhancers with their target genes based on their colocalization within the same topological domains. However, the mechanisms that regulate how enhancers specifically activate some genes but not others within a given domain remain unclear. In this Review, we discuss recent insights into the factors controlling enhancer specificity, including the genetic composition of enhancers and promoters, the linear and 3D distance between enhancers and their target genes, and cell-type specific chromatin landscapes. We also discuss how elucidating the molecular principles of enhancer specificity might help us to better understand and predict the pathological consequences of human genetic, epigenetic and structural variants.
Dissecting mechanisms of chamber-specific cardiac differentiation and its perturbation following retinoic acid exposure
Authors: Gonzalez David M. , Schrode Nadine , Ebrahim Tasneem A. M. , Broguiere Nicolas , Rossi Giuliana , Drakhlis Lika , Zweigerdt Robert , Lutolf Matthias P. , Beaumont Kristin G. , Sebra Robert , Dubois Nicole C.
Published: June 2022

The specification of distinct cardiac lineages occurs before chamber formation and acquisition of bona fide atrial or ventricular identity. However, the mechanisms underlying these early specification events remain poorly understood. Here, we performed single cell analysis at the murine cardiac crescent, primitive heart tube and heart tube stages to uncover the transcriptional mechanisms underlying formation of atrial and ventricular cells. We find that progression towards differentiated cardiomyocytes occurs primarily based on heart field progenitor identity, and that progenitors contribute to ventricular or atrial identity through distinct differentiation mechanisms. We identify new candidate markers that define such differentiation processes and examine their expression dynamics using computational lineage trajectory methods. We further show that exposure to exogenous retinoic acid causes defects in ventricular chamber size, dysregulation in FGF signaling and a shunt in differentiation towards orthogonal lineages. Retinoic acid also causes defects in cell-cycle exit resulting in formation of hypomorphic ventricles. Collectively, our data identify, at a single cell level, distinct lineage trajectories during cardiac specification and differentiation, and the precise effects of manipulating cardiac progenitor patterning via retinoic acid signaling.
Features of smaller ribosomes in candidate phyla radiation (CPR) bacteria revealed with a molecular evolutionary analysis
Authors: Tsurumaki Megumi , Saito Motofumi , Tomita Masaru , Kanai Akio
Published: June 2022

The candidate phyla radiation (CPR) is a large bacterial group consisting mainly of uncultured lineages. They have small cells and small genomes, and they often lack ribosomal proteins uL1, bL9, and/or uL30, which are basically ubiquitous in non-CPR bacteria. Here, we comprehensively analyzed the genomic information on CPR bacteria and identified their unique properties. The distribution of protein lengths in CPR bacteria peaks at around 100–150 amino acids, whereas the position of the peak varies in the range of 100–300 amino acids in free-living non-CPR bacteria, and at around 100–200 amino acids in most symbiotic non-CPR bacteria. These results show that the proteins of CPR bacteria are smaller, on average, than those of free-living non-CPR bacteria, like those of symbiotic non-CPR bacteria. We found that ribosomal proteins bL28, uL29, bL32, and bL33 have been lost in CPR bacteria in a taxonomic lineage-specific manner. Moreover, the sequences of approximately half of all ribosomal proteins of CPR differ, in part, from those of non-CPR bacteria, with missing regions or specifically added regions. We also found that several regions in the 16S, 23S, and 5S rRNAs of CPR bacteria are lacking, which presumably caused the total predicted lengths of the three rRNAs of CPR bacteria to be smaller than those of non-CPR bacteria. The regions missing in the CPR ribosomal proteins and rRNAs are located near the surface of the ribosome, and some are close to one another. These observations suggest that ribosomes are smaller in CPR bacteria than those in free-living non-CPR bacteria, with simplified surface structures.
Αξιολόγηση της συνεργατικής (αμοιβαίας) μεθόδου διδασκαλίας στην αντισφαίριση σε παιδιά ηλικίας 12-15 χρονών
Authors: Κυριτσόπουλος Δημήτριος
Published: June 2022

Σκοπός της διδακτορικής διατριβής ήταν να αξιολογηθεί η Αμοιβαία Μέθοδος Διδασκαλίας (στο εξής Α.Μ.Δ.), σε βασικά χτυπήματα της αντισφαίρισης, όπως είναι το forehand, backhand και service, και συγχρόνως να διερευνηθεί κατά πόσο επηρεάζει την ανάπτυξη των κινητικών δεξιοτήτων. Στο πρώτο μέρος της έρευνας συμμετείχαν 102 παιδιά ηλικίας 14-15 ετών χωρίς καμία προηγούμενη εμπειρία στην Αντισφαίριση. Πραγματοποιήθηκαν 12 μαθήματα για τα δύο πρώτα χτυπήματα (forehand και backhand) και στη συνέχεια 8 μαθήματα αντίστοιχα για το service σε μαθητές-τριες 6 τμημάτων της Γ΄ Γυμνασίου σε 2 διαφορετικά σχολεία. Τα μέλη του δείγματος κατανεμήθηκαν σε δύο ομάδες (Π.Ο. και Ο.Ε.). Στα τμήματα της Π.Ο. σχηματίστηκαν ζευγάρια μαθητών-τριών ακολουθώντας πιστά την διαδικασία του στυλ της Α.Μ.Δ. χρησιμοποιώντας το φύλλο κριτηρίων που σχεδιάστηκε από τον ερευνητή-εκπαιδευτικό. Η επεξεργασία των δεδομένων πραγματοποιήθηκε στο στατιστικό πρόγραμμα IBM SPSS 24 με την χρησιμοποίηση του t-test για εξαρτημένα δείγματα πριν και μετά την παρέμβαση με επίπεδο σημαντικότητας το (p<.05). Η έρευνα έδειξε ότι η επίδοση των συμμετεχόντων ήταν βελτιωμένη στην αντισφαίριση στα χτυπήματα forehand, backhand και service και στις δύο ομάδες (ιδιαιτέρως στην Π.Ο.), αφού εντοπίστηκε στατιστικά σημαντική διαφορά στα σκορ (αύξηση του μέσου όρου των συνεχόμενων χτυπημάτων και της ευστοχίας). Στο δεύτερο μέρος της έρευνας το δείγμα αποτέλεσαν 408 μαθητές- τριες ηλικίας 12-15 ετών, 204 φοιτούντες σε Γυμνάσια των Δήμων Τανάγρας και Χαλκιδέων, καθώς και 204 προερχόμενοι από συλλόγους αντισφαίρισης των Δήμων Λαρισαίων, Χαλκιδέων και Θηβών. Εφαρμόσθηκε αναλυτικό σχέδιο Α.Μ.Δ. μίας (1) ώρας στα 3 βασικά προαναφερθέντα χτυπήματα της αντισφαίρισης και στο τέλος δόθηκε στους συμμετέχοντες, ως εργαλείο μέτρησης, ανώνυμα και εμπιστευτικά το ερωτηματολόγιο Intrinsic Motivation Inventory (IMI) του McAuley et al. (1989). Η επεξεργασία των δεδομένων μέσω ανάλυσης διακύμανσης μονής κατεύθυνσης (One-Way Anova) έδειξε: το φύλο επηρεάζει τη φυσική δραστηριότητα, υπάρχει στατιστικά σημαντική διαφορά μεταξύ των τάξεων Α΄ και Β΄ Γυμνασίου στην προσπάθεια η οποία οφείλεται σε κάποιον συστηματικό παράγοντα και η ευχαρίστηση, η προσπάθεια, η στάση/ άποψη ως προς την αντισφαίριση, η πρόθεση για δοκιμή της αντισφαίρισης αλλά και η φυσική δραστηριότητα επηρεάζονται από το αν οι συμμετέχοντες προέρχονται από Γυμνάσια ή Συλλόγους Αντισφαίρισης, και ταυτόχρονα από το αν οι συμμετέχοντες είναι αθλητές/ τριες ή όχι. Επιπρόσθετα εξήχθη το συμπέρασμα ότι η στενή σχέση που αναπτύσσεται κατά τη διδασκαλία ανά ζεύγη με την Αμοιβαία Μέθοδο με αυξημένα τα χαρακτηριστικά της συνεργασίας και της ανατροφοδότησης, παρακινεί και επιδρά θετικά στην εκμάθηση των τριών κινητικών δεξιοτήτων του αθλήματος υποδηλώνοντας την αποτελεσματικότητά του, αλλά και την ανάπτυξη του ομαδικού πνεύματος.
Extension of the PRISMA 2020 statement for living systematic reviews (LSRs): protocol
Authors: Kahale Lara A , Piechotta Vanessa , McKenzie Joanne E , Dorando Elena , Iannizzi Claire , Barker James M , Page Matthew J , Skoetz Nicole , Akl Elie A
Published: June 2022

Background: While the PRISMA 2020 statement is intended to guide the reporting of original systematic reviews, updated systematic reviews, and living systematic reviews (LSRs), its explanation and elaboration document notes that additional considerations for updated systematic reviews and LSRs may need to be addressed. This paper reports the protocol for developing an extension of the PRISMA 2020 statement for LSRs.

Methods: We will follow the EQUATOR Network’s guidance for developing health research reporting guidelines. We will review the literature to identify possible items of the PRISMA 2020 checklist that need modification, as well as new items that need to be added. Then, we will survey representatives of different stakeholder groups for their views on the proposed modifications of the PRISMA 2020 checklist. We will summarize, present, and discuss the results of the survey in an online meeting, aiming to reach consensus on the content of the LSR extension. We will then draft the checklist, explanation and elaboration for each item, and flow diagram for the PRISMA 2020 extension. Then, we will share these initial documents with stakeholder representatives for final feedback and approval.

Discussion: We anticipate that the PRISMA 2020 extension for LSRs will benefit LSR authors, editors, and peer reviewers of LSRs, as well as different users of LSRs, including guideline developers, policy makers, healthcare providers, patients, and other stakeholders.
Online academic satisfaction during the COVID-19 pandemic in medical students: role of sleep, emotions, college adjustment, and digital skills
Authors: Medina-Ramirez Sebastian A. , Rojas-Humpire Ricardo , Canaza Josue F. , Hernandez Fiorella , Huancahuire-Vega Salomón
Published: June 2022

Background: The measures taken to contain the COVID-19 pandemic, led to significant changes in university education, resulting in the new normal standard of virtual teaching in many undergraduate medical schools worldwide. Therefore, the aim of this paper was to determine the factors related to academic satisfaction with virtual teaching in medical students during the COVID-19 pandemic.

Methods: A cross-sectional-analytical study was conducted on medical students at a private university in Peru, through self-reported questionnaires divided into sociodemographic data and variables of interest that could influence academic satisfaction during the pandemic. To evaluate possible factors related to academic satisfaction, stepwise regression models were performed for both sexes.

Results: In total, data from 310 medical students, 117 males and 193 females, were analyzed. Academic satisfaction reached a score of 11.2 ± 2.9, which was similar in both sexes. The best regression model for males (AIC: 544.32; RMSE: 2.42; R2: 0.30) showed that adaptation to university life (favorable change) and depression (unfavorable change) explained 30% of changes in students' academic satisfaction. While in females (AIC: 907.59; RMSE: 2.49; R 2: 0.22) the model integrated favorable factors such as adjustment to college life and anxiety; while depression and poor sleep quality were unfavorable factors.

Conclusion: Factors that contributed to academic satisfaction in medical students were determined in this study, which differed by gender. Thus, it is important to take into account the particularities of male and female medical students in order to improve their academic satisfaction during their university careers.
Arrest for Debt in Late Elizabethan and Early Stuart London
Authors: Minson Stuart
Published: June 2022

Arrest on civil process, especially for debt, became an increasingly important motif in late Elizabethan and early Stuart literature, especially Jacobean drama. In the second half of the sixteenth century, rates of litigation skyrocketed, arrest on first instance became common, and a series of bankruptcy acts exacerbated the inequities of debt proceedings. Moreover, the crown’s efforts to mitigate problems of imprisonment for debt made arrest a flashpoint between competing movements for legal reform. In these contexts, dramatists paid new attention to arrest practices, regularly representing them as illegitimate and open to abuse. The motif of arrest for debt had particular power in dramatic works because the legal act itself was inherently performative.
The Consequences of Rating Inflation on Platforms: Evidence from a Quasi-Experiment
Authors: Aziz Arslan , Li Hui , Telang Rahul
Published: June 2022

Informative online ratings enable digital platforms to reduce the search cost for buyers to find good sellers. However, rating inflation, a phenomenon in which average rating increases and rating variance across listings decreases, threatens the informativeness of ratings. We empirically identify the consequences of rating inflation by conducting a quasi-experiment with a digital platform that exogenously changed its rating display rule in a treated neighborhood, which resulted in rating inflation. Using a differences-in-differences approach, we find that platforms benefit from one aspect of rating inflation: user purchases and seller sales increase because of the increased average rating. However, they also face negative consequences: rating inflation causes a decrease in user trial and a greater concentration of sales among popular restaurants. Overall, our results illustrate the potential consequences of rating inflation that platforms need to consider when designing and managing their rating system.
Spectral upper bound on the quantum $k$-independence number of a graph
Authors: Wocjan Pawel , Elphick Clive , Abiad Aida
Published: June 2022

A well known upper bound for the independence number $\alpha(G)$ of a graph $G$, due to Cvetkovi ́c, is that \begin{equation*}\alpha(G) \le n^0 + \min\{n^+ , n^-\}\end{equation*}where $(n^+, n^0, n^-)$ is the inertia of $G$. We prove that this bound is also an upper bound for the quantum independence number $\alpha_q$(G), where $\alpha_q(G) \ge \alpha(G)$ and for some graphs $\alpha_q(G) \gg \alpha(G)$. We identify numerous graphs for which $\alpha(G) = \alpha_q(G)$, thus increasing the number of graphs for which $\alpha_q$ is known. We also demonstrate that there are graphs for which the above bound is not exact with any Hermitian weight matrix, for $\alpha(G)$ and $\alpha_q(G)$. Finally, we show this result in the more general context of spectral bounds for the quantum $k$-independence number, where the $k$-independence number is the maximum size of a set of vertices at pairwise distance greater than $k$.
K-subdirect sums of Nekrasov matrices
Authors: Lyu Zhen-Hua , Wang Xueru , Wen Lishu
Published: June 2022

In this paper, we give a sufficient and necessary condition for the subdirect sum of a Nekrasov matrix and a strictly diagonally dominant matrix being still a Nekrasov matrix. Adopting this sufficient and necessary condition, we present several simple sufficient conditions ensuring that the subdirect sum of Nekrasov matrices is in the same class. Examples are reported to illustrate the theoretical results.
Systemic medical complications following joint replacement: a review of the evidence
Authors: Curlewis K , Leung B , Sinclair L , Thornhill C , Chan G , Ricketts D
Published: June 2022

Introduction

Arthroplasty procedures are commonly performed in the UK. Informed consent is required for each procedure. To obtain informed consent the patient and their surgeon should discuss the risks and benefits of the proposed operation. This discussion should include both regional and systemic complication rates. Regional complications of arthroplasty are generally well documented in the literature. Systemic medical complications are less well described. This lack of accurate data could make it difficult for the treating surgeon to obtain valid consent. The aim of this paper was to review and compare the literature regarding the rate of systemic medical complications after common arthroplasty procedures.

Methods

A literature search was conducted using the PubMed, Cochrane Library and MEDLINE databases. Studies regarding the systemic medical complications and mortality rate of joint replacement were included.

Findings

We found that systemic complications were more frequent than regional complications following arthroplasty. The systemic complication rates were: hip, 5.1%; knee, 6.9%; ankle, 3.0%; shoulder, 11.2%; elbow, 8.5%; and wrist, 0%. Mortality rates for arthroplasty procedures were: hip, 0.3%; knee, 0.2%; ankle, 0.3%; shoulder, 0.3%; elbow, 0.2%; and wrist, 0%.

Conclusions

The most common systemic medical complication following arthroplasty was venous thromboembolism. Preoperative comorbidity was the most important risk factor for both postoperative mortality and systemic medical complications following arthroplasty procedures. We recommend that to obtain informed consent the given rates of systemic medical complications of joint replacement should be discussed and documented.
Interpretation of flight data from a fixed-wing UAV system
dedicated to flying over high voltage lines
Authors: VIDAN Cristian , POP Sebastian
Published: June 2022

This paper analyzes and presents an interpretation of the flight data resulting from a flight of
a fixed-wing UAV system that was designed from the beginning to perform support missions in order to
monitor losses on critical infrastructure in Romania; in this particular case it monitors the losses on
the high voltage powerlines in order to detect Corona discharge. Also, for the safety of the flight, in
order to design the flight route, aspects regarding the altitude, the relief and the possible obstacles that
may appear on the flight route were analyzed. After designing the flight route in accordance with the
path of a 400 kV high voltage overhead powerlines, the flight was performed and the flight parameters
were analyzed in order to validate the system. In conclusion, from the analysis of UAV parameters and
its behavior in case of a real flight on high voltage lines it can be stated that UAV systems with fixed
wing are recommended for flight on overhead powerlines, behave stably, sensors on board are not
influenced by electromagnetic field of the powerline, so that this type of UAV system does not endanger
the physical integrity of the overhead powerlines or the system operation.
Wernher Von Braun’s Pioneering Work in Modelling and Testing Liquid-Propellant Rockets
Authors: ZAGANESCU Nicolae-Florin , ZAGANESCU Rodica , GHEORGHE Constantin-Marcian
Published: June 2022

This paper presents a view on how Dr. Wernher Von Braun laid the basis for realistic modelling and testing liquid-propellants rockets, by his PhD Thesis – a secret document in 1934, which remained classified until 1960. Understanding that better mathematical modelling is needed if these rockets are to become spaceflight vehicles, he clarified in his thesis essential issues like: maximum achievable rocket speed; Laval nozzle thrust gain; polytropic processes in the combustion chamber and nozzle; influence of equilibrium and dissociation reactions; original measurement systems for rockets test stand; engineering solutions adequate for series production of the combustion chamber – reactive nozzle assembly. The thesis provided a theoretical and experimental basis for a new concept of the rocket, having a lightweight structure; low tanks pressure; high-pressure pumps and injectors; low start speed; rocket stabilization by gyroscopic means or by active jet controls; longer engine burning time; higher jet speed. Numerous tests made even with a fully assembled rocket (the “Aggregate-I”), improved mathematical model accuracy (e.g., the maximum achievable altitude predicted for the “Aggregate-II” rocket was confirmed later in-flight tests).