bluuebunny/crossref_metadata_2025 huggingface dataset:
Phylogenomic Analyses of Alismatales Shed Light into Adaptations to Aquatic Environments
Authors: Chen Ling-Yun , Lu Bei , Morales-Briones Diego F. , Moody Michael L. , Liu Fan , Hu Guang-Wan , Huang Chien-Hsun , Chen Jin-Ming , Wang Qing-Feng
Published: April 2022

Land plants first evolved from freshwater algae, and flowering plants returned to water as early as the Cretaceous and multiple times subsequently. Alismatales is the largest clade of aquatic angiosperms including all marine angiosperms, as well as terrestrial plants. We used Alismatales to explore plant adaptations to aquatic environments by analyzing a data set that included 95 samples (89 Alismatales species) covering four genomes and 91 transcriptomes (59 generated in this study). To provide a basis for investigating adaptations, we assessed phylogenetic conflict and whole-genome duplication (WGD) events in Alismatales. We recovered a relationship for the three main clades in Alismatales as (Tofieldiaceae, Araceae) + core Alismatids. We also found phylogenetic conflict among the three main clades that was best explained by incomplete lineage sorting and introgression. Overall, we identified 18 putative WGD events across Alismatales. One of them occurred at the most recent common ancestor of core Alismatids, and three occurred at seagrass lineages. We also found that lineage and life-form were both important for different evolutionary patterns for the genes related to freshwater and marine adaptation. For example, several light- or ethylene-related genes were lost in the seagrass Zosteraceae, but are present in other seagrasses and freshwater species. Stomata-related genes were lost in both submersed freshwater species and seagrasses. Nicotianamine synthase genes, which are important in iron intake, expanded in both submersed freshwater species and seagrasses. Our results advance the understanding of the adaptation to aquatic environments and WGDs using phylogenomics.
Attribution of Cancer Origins to Endogenous, Exogenous, and Preventable Mutational Processes
Authors: Cannataro Vincent L. , Mandell Jeffrey D. , Townsend Jeffrey P.
Published: April 2022

Mutational processes in tumors create distinctive patterns of mutations, composed of neutral “passenger” mutations and oncogenic drivers that have quantifiable effects on the proliferation and survival of cancer cell lineages. Increases in proliferation and survival are mediated by natural selection, which can be quantified by comparing the frequency at which we detect substitutions to the frequency at which we expect to detect substitutions assuming neutrality. Most of the variants detectable with whole-exome sequencing in tumors are neutral or nearly neutral in effect, and thus the processes generating the majority of mutations may not be the primary sources of the tumorigenic mutations. Across 24 cancer types, we identify the contributions of mutational processes to each oncogenic variant and quantify the degree to which each process contributes to tumorigenesis. We demonstrate that the origination of variants driving melanomas and lung cancers is predominantly attributable to the preventable, exogenous mutational processes associated with ultraviolet light and tobacco exposure, respectively, whereas the origination of selected variants in gliomas and prostate adenocarcinomas is largely attributable to endogenous processes associated with aging. Preventable mutations associated with pathogen exposure and apolipoprotein B mRNA-editing enzyme activity account for a large proportion of the cancer effect within head-and-neck, bladder, cervical, and breast cancers. These attributions complement epidemiological approaches—revealing the burden of cancer driven by single-nucleotide variants caused by either endogenous or exogenous, nonpreventable, or preventable processes, and crucially inform public health strategies.
An atlas of posttranslational modifications on RNA binding proteins
Authors: England Whitney E , Wang Jingtian , Chen Siwei , Baldi Pierre , Flynn Ryan A , Spitale Robert C
Published: April 2022

RNA structure and function are intimately tied to RNA binding protein recognition and regulation. Posttranslational modifications are chemical modifications which can control protein biology. The role of PTMs in the regulation RBPs is not well understood, in part due to a lacking analysis of PTM deposition on RBPs. Herein, we present an analysis of posttranslational modifications (PTMs) on RNA binding proteins (RBPs; a PTM RBP Atlas). We curate published datasets and primary literature to understand the landscape of PTMs and use protein–protein interaction data to understand and potentially provide a framework for understanding which enzymes are controlling PTM deposition and removal on the RBP landscape. Intersection of our data with The Cancer Genome Atlas also provides researchers understanding of mutations that would alter PTM deposition. Additional characterization of the RNA–protein interface provided from in-cell UV crosslinking experiments provides a framework for hypotheses about which PTMs could be regulating RNA binding and thus RBP function. Finally, we provide an online database for our data that is easy to use for the community. It is our hope our efforts will provide researchers will an invaluable tool to test the function of PTMs controlling RBP function and thus RNA biology.
Active endogenous retroviral elements in human pluripotent stem cells play a role in regulating host gene expression
Authors: Zhang Tianzhe , Zheng Ran , Li Mao , Yan Chenchao , Lan Xianchun , Tong Bei , Lu Pei , Jiang Wei
Published: April 2022

Human endogenous retroviruses, also called LTR elements, can be bound by transcription factors and marked by different histone modifications in different biological contexts. Recently, individual LTR or certain subclasses of LTRs such as LTR7/HERVH and LTR5_Hs/HERVK families have been identified as cis-regulatory elements. However, there are still many LTR elements with unknown functions. Here, we dissected the landscape of histone modifications and regulatory map of LTRs by integrating 98 ChIP-seq data in human embryonic stem cells (ESCs), and annotated the active LTRs enriching enhancer/promoter-related histone marks. Notably, we found that MER57E3 functionally acted as proximal regulatory element to activate respective ZNF gene. Additionally, HERVK transcript could mainly function in nucleus to activate the adjacent genes. Since LTR5_Hs/LTR5 was bound by many early embryo-specific transcription factors, we further investigated the expression dynamics in different pluripotent states. LTR5_Hs/LTR5/HERVK exhibited higher expression level in naïve ESCs and extended pluripotent stem cells (EPSCs). Functionally, the LTR5_Hs/LTR5 with high activity could serve as a distal enhancer to regulate the host genes. Ultimately, our study not only provides a comprehensive regulatory map of LTRs in human ESCs, but also explores the regulatory models of MER57E3 and LTR5_Hs/LTR5 in host genome.
Gene-SCOUT: identifying genes with similar continuous trait fingerprints from phenome-wide association analyses
Authors: Middleton Lawrence , Harper Andrew R , Nag Abhishek , Wang Quanli , Reznichenko Anna , Vitsios Dimitrios , Petrovski Slavé
Published: April 2022

Large-scale phenome-wide association studies performed using densely-phenotyped cohorts such as the UK Biobank (UKB), reveal many statistically robust gene-phenotype relationships for both clinical and continuous traits. Here, we present Gene-SCOUT, a tool used to identify genes with similar continuous trait fingerprints to a gene of interest. A fingerprint reflects the continuous traits identified to be statistically associated with a gene of interest based on multiple underlying rare variant genetic architectures. Similarities between genes are evaluated by the cosine similarity measure, to capture concordant effect directionality, elucidating clusters of genes in a high dimensional space. The underlying gene-biomarker population-scale association statistics were obtained from a gene-level rare variant collapsing analysis performed on over 1500 continuous traits using 394 692 UKB participant exomes, with additional metabolomic trait associations provided through Nightingale Health's recent study of 121 394 of these participants. We demonstrate that gene similarity estimates from Gene-SCOUT provide stronger enrichments for clinical traits compared to existing methods. Furthermore, we provide a fully interactive web-resource (http://genescout.public.cgr.astrazeneca.com) to explore the pre-calculated exome-wide similarities. This resource enables a user to examine the biological relevance of the most similar genes for Gene Ontology (GO) enrichment and UKB clinical trait enrichment statistics, as well as a detailed breakdown of the traits underpinning a given fingerprint.
Coexpression reveals conserved gene programs that co-vary with cell type across kingdoms
Authors: Crow Megan , Suresh Hamsini , Lee John , Gillis Jesse
Published: April 2022

What makes a mouse a mouse, and not a hamster? Differences in gene regulation between the two organisms play a critical role. Comparative analysis of gene coexpression networks provides a general framework for investigating the evolution of gene regulation across species. Here, we compare coexpression networks from 37 species and quantify the conservation of gene activity 1) as a function of evolutionary time, 2) across orthology prediction algorithms, and 3) with reference to cell- and tissue-specificity. We find that ancient genes are expressed in multiple cell types and have well conserved coexpression patterns, however they are expressed at different levels across cell types. Thus, differential regulation of ancient gene programs contributes to transcriptional cell identity. We propose that this differential regulation may play a role in cell diversification in both the animal and plant kingdoms.
BioUML—towards a universal research platform
Authors: Kolpakov Fedor , Akberdin Ilya , Kiselev Ilya , Kolmykov Semyon , Kondrakhin Yury , Kulyashov Mikhail , Kutumova Elena , Pintus Sergey , Ryabova Anna , Sharipov Ruslan , Yevshin Ivan , Zhatchenko Sergey , Kel Alexander
Published: April 2022

BioUML (https://www.biouml.org)—is a web-based integrated platform for systems biology and data analysis. It supports visual modelling and construction of hierarchical biological models that allow us to construct the most complex modular models of blood pressure regulation, skeletal muscle metabolism, COVID-19 epidemiology. BioUML has been integrated with git repositories where users can store their models and other data. We have also expanded the capabilities of BioUML for data analysis and visualization of biomedical data: (i) any programs and Jupyter kernels can be plugged into the BioUML platform using Docker technology; (ii) BioUML is integrated with the Galaxy and Galaxy Tool Shed; (iii) BioUML provides two-way integration with R and Python (Jupyter notebooks): scripts can be executed on the BioUML web pages, and BioUML functions can be called from scripts; (iv) using plug-in architecture, specialized viewers and editors can be added. For example, powerful genome browsers as well as viewers for molecular 3D structure are integrated in this way; (v) BioUML supports data analyses using workflows (own format, Galaxy, CWL, BPMN, nextFlow). Using these capabilities, we have initiated a new branch of the BioUML development—u-science—a universal scientific platform that can be configured for specific research requirements.
SCF ubiquitin E3 ligase regulates DNA double-strand breaks in early meiotic recombination
Authors: Guan Yongjuan , Lin Huijuan , Leu N Adrian , Ruthel Gordon , Fuchs Serge Y , Busino Luca , Luo Mengcheng , Wang P Jeremy
Published: April 2022

Homeostasis of meiotic DNA double strand breaks (DSB) is critical for germline genome integrity and homologous recombination. Here we demonstrate an essential role for SKP1, a constitutive subunit of the SCF (SKP1-Cullin-F-box) ubiquitin E3 ligase, in early meiotic processes. SKP1 restrains accumulation of HORMAD1 and the pre-DSB complex (IHO1-REC114-MEI4) on the chromosome axis in meiotic germ cells. Loss of SKP1 prior to meiosis leads to aberrant localization of DSB repair proteins and a failure in synapsis initiation in meiosis of both males and females. Furthermore, SKP1 is crucial for sister chromatid cohesion during the pre-meiotic S-phase. Mechanistically, FBXO47, a meiosis-specific F-box protein, interacts with SKP1 and HORMAD1 and targets HORMAD1 for polyubiquitination and degradation in HEK293T cells. Our results support a model wherein the SCF ubiquitin E3 ligase prevents hyperactive DSB formation through proteasome-mediated degradation of HORMAD1 and subsequent modulation of the pre-DSB complex during meiosis.
End-to-end interstitial fibrosis assessment of kidney biopsies with a machine learning-based model
Authors: Liu Zhi-Yong , Lin Chi-Hung , Wang Hsiang-Sheng , Wen Mei-Chin , Lin Wei-Chou , Huang Shun-Chen , Tu Kun-Hua , Kuo Chang-Fu , Chen Tai-Di
Published: April 2022

Background

The extent of interstitial fibrosis in the kidney not only correlates with renal function at the time of biopsy but also predicts future renal outcome. However, its assessment by pathologists lacks good agreement. The aim of this study is to construct a machine learning-based model that enables automatic and reliable assessment of interstitial fibrosis in human kidney biopsies.

Methods

Validated cortex, glomerulus and tubule segmentation algorithms were incorporated into a single model to assess the extent of interstitial fibrosis. The model performances were compared with expert renal pathologists and correlated with patients’ renal functional data.

Results

Compared with human raters, the model had the best agreement [intraclass correlation coefficient (ICC) 0.90] to the reference in 50 test cases. The model also had a low mean bias and the narrowest 95% limits of agreement. The model was robust against colour variation on images obtained at different times, through different scanners, or from outside institutions with excellent ICCs of 0.92–0.97. The model showed significantly better test-retest reliability (ICC 0.98) than humans (ICC 0.76–0.94) and the amount of interstitial fibrosis inferred by the model strongly correlated with 405 patients’ serum creatinine (r = 0.65–0.67) and estimated glomerular filtration rate (r = −0.74 to −0.76).

Conclusions

This study demonstrated that a trained machine learning-based model can faithfully simulate the whole process of interstitial fibrosis assessment, which traditionally can only be carried out by renal pathologists. Our data suggested that such a model may provide more reliable results, thus enabling precision medicine.
Gender Differences in Reasons for Using Electronic Cigarettes: A Systematic Review
Authors: Bedi Mannat K , Bedi Danishi K , Ledgerwood David M
Published: April 2022

Introduction

Differential reasons for electronic cigarette (e-cigarette) use for men and women have seldom been examined, and there is no systematic overview of this research literature.

Aims and Methods

The aim of this review is to conduct a systematic review of the literature to identify gender differences in the reasons for e-cigarette use. Systematic searches covered in three databases found 866 unique articles: Web of Science, PubMed, and PsycINFO. Twenty-six studies met the inclusion criteria and were reviewed. Reasons for e-cigarette use were sorted into 17 distinct categories.

Results and Conclusions

Sixteen studies identified statistically significant differences in reasons between men and women. Frequently assessed reasons for e-cigarette use across studies included Health/Smoking Cessation, Experimentation/Curiosity, Enjoyment/Pleasure, Use in Specific Locations, Acceptable to Others, and Cost. Of those that identified statistically significant differences in reasons between men and women, the findings varied considerably, and some reasons for e-cigarette use were found to be significant in only one or two studies. Most of the reasons identified were only measured in a small number of studies, complicating our ability to make intervention recommendations based on gender. Additionally, we limited our literature search to peer-reviewed studies. Of the reason categories that did find significant differences between gender, such as reasons related to Health/Smoking Cessation, the outcomes were not consistent across studies. Future studies are needed to identify potentially important differences in the reasons for e-cigarette use among men and women.

Implications

This systematic review aims to uncover gender differences in e-cigarette use to understand important differences in motivation for use that may help us better understand strategies for prevention and treatment of tobacco use disorder. This review is the first on this topic and could provide further insight on patterns of e-cigarette use across gender.
Food insecurity and adverse childhood experiences: a systematic review
Authors: Royer Michael F , Ojinnaka Chinedum O , Zhang Xing , Thornton Anthony G , Blackhorse Kimberly , Bruening Meg
Published: April 2022

Context

Food insecurity (FI) and adverse childhood experiences (ACEs) disproportionally affect vulnerable populations and are key social determinants of health that predict nutrition-related outcomes. It is critical to understand how FI and ACEs are interrelated so prevention studies can be designed to better promote health equity.

Objective

A systematic literature review was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses to determine the association between FI and ACEs.

Data Sources

Google Scholar, PubMed, and Scopus databases were used to find articles relevant to the study. Inclusion criteria included quantitative, qualitative, or mixed-methods studies of humans, using an experimental or observational research design to examine the relationship between FI and ACEs using the validated ACEs measure in its entirety.

Data Extraction

Studies were assessed for study design, data set, population descriptions, and results of the association between FI and ACEs. Additionally, all included studies were assessed for bias and validity.

Data Analysis

A total of 10 articles were included in the systematic review. Of those articles, 9 were reports on cross-sectional studies, and 1 reported on a longitudinal study; however, all 10 studies used a retrospective approach. Six studies were conducted using secondary data. Results reported in all 10 articles indicated a significant positive association between FI and ACEs. Evidence indicated greater odds of FI among individuals with high ACE scores, with most studies indicating a dose-response or a threshold effect of higher ACEs being associated with more severe FI.

Conclusions

FI and ACEs are consistently related. Prevention study interventions should be designed to address FI and problems stemming from ACEs. Filling knowledge gaps regarding the relationship between ACEs and FI is critical for designing nutrition interventions that promote food security, prevent the occurrence of ACEs, and improve health outcomes among vulnerable populations with high ACEs.

Systematic Review Registration

PROSPERO registration no.: CRD42020210106.
A Quality Initiative to Improve Postdischarge Care for Patients on Outpatient Parenteral Antimicrobial Therapy
Authors: Certain Laura K , Benefield Russell J , Newman Michael , Zhang Mingyuan , Thomas Frank O
Published: April 2022

Background

Patients discharged from the hospital on outpatient parenteral antimicrobial therapy (OPAT) require close monitoring, including weekly blood tests and an early posthospital follow-up visit. However, because patients often receive OPAT in a separate healthcare system from where they received inpatient care, the OPAT plan often fails, with less than 75% of OPAT patients receiving the recommended laboratory monitoring. We sought to determine whether changing our inpatient OPAT documentation method would improve postdischarge care.

Methods

As a quality improvement initiative, we conducted 2 Plan-Do-Study-Act interventions on our OPAT documentation. Our first intervention was to create a standardized OPAT Progress Note, and our second was to turn that note into a SmartForm (Epic) with discrete fields for the key information. We examined the effects of these changes on the rate of completion of recommended laboratory monitoring, attendance at outpatient follow-up visits, and 30-day readmission rates.

Results

Changing our documentation to a standardized Progress Note and then to a SmartForm with discrete fields led to an increase in the proportion of patients with a serum creatinine checked within 10 days of discharge (from 63% to 71% to 73%) and who attended an infectious disease clinic visit within 3 weeks of discharge (from 21% to 36% to 47%). However, the rate of readmissions for OPAT-related problems did not change, nor did a composite outcome of 30-day mortality/unplanned readmission.

Conclusions

Changes in how and where care plans are documented in the inpatient medical record can have significant effects on patient care outcomes after discharge.
Larotrectinib Treatment for Patients With TRK Fusion-Positive Salivary Gland Cancers
Authors: Le Xiuning , Baik Christina , Bauman Jessica , Gilbert Jill , Brose Marcia S , Grilley-Olson Juneko E , Patil Tejas , McDermott Ray , Raez Luis E , Johnson Jennifer M , Shen Lin , Tahara Makoto , Ho Alan L , Norenberg Ricarda , Dima Laura , Brega Nicoletta , Drilon Alexander , Hong David S
Published: April 2022

Background

Larotrectinib is a first-in-class, highly selective, and central nervous system-active tropomyosin receptor kinase (TRK) inhibitor approved for the treatment of adult and pediatric patients with TRK fusion cancer. We report the efficacy and safety of larotrectinib in patients with TRK fusion-positive salivary gland cancers.

Patients and Methods

Patients with TRK fusion-positive salivary gland cancer treated with larotrectinib were identified from two clinical trials (NCT02122913 and NCT02576431). Patients received larotrectinib 100 mg twice daily (BID) except for one patient who received 150 mg BID in the phase I trial. The primary endpoint was objective response rate (ORR) as assessed by the investigator using Response Evaluation Criteria in Solid Tumors version 1.1.

Results

At the data cut-off (July 20, 2020), 24 patients with TRK fusion-positive salivary gland cancer had been treated. The most common histologies were secretory carcinoma (54%), adenocarcinoma (25%), and mucoepidermoid carcinoma (13%). All 24 patients had an ETV6-NTRK3 gene fusion. The ORR was 92% (95% confidence interval, 73-99). Best overall response was complete response in three (13%) patients, partial response in 19 (79%), and progressive disease in two (8%). The rate of progression-free survival at 24 months was 78% (median follow-up 30.9 months). Most treatment-related adverse events (AEs) were grade 1-2, and no patients discontinued treatment due to AEs.

Conclusion

Larotrectinib demonstrated robust and durable efficacy in patients with TRK fusion-positive salivary gland tumors of various histologies, and a favorable safety profile. These findings support NTRK gene fusion testing in patients with advanced salivary gland cancers.

ClinicalTrials.gov numbers

NCT02122913 and NCT02576431.
Degradation of dead cladoceran zooplankton and their contribution to organic carbon cycling in stratified lakes: field observation and model prediction
Authors: Tolomeev Aleksandr P , Dubovskaya Olga P , Kirillin Georgiy , Buseva Zhanna , Kolmakova Olesya V , Grossart Hans-Peter , Tang Kam W , Gladyshev Michail I
Published: April 2022

The contribution of dead zooplankton biomass to carbon cycle in aquatic ecosystems is practically unknown. Using abundance data of zooplankton in water column and dead zooplankton in sediment traps in Lake Stechlin, an ecological-mathematical model was developed to simulate the abundance and sinking of zooplankton carcasses and predict the related release of labile organic matter (LOM) into the water column. We found species-specific differences in mortality rate of the dominant zooplankton: Daphnia cucullata, Bosmina coregoni and Diaphanosoma brachyurum (0.008, 0.129 and 0.020 day−1, respectively) and differences in their carcass sinking velocities in metalimnion (and hypolimnion): 2.1 (7.64), 14.0 (19.5) and 1.1 (5.9) m day−1, respectively. Our model simulating formation and degradation processes of dead zooplankton predicted a bimodal distribution of the released LOM: epilimnic and metalimnic peaks of comparable intensity, ca. 1 mg DW m−3 day−1. Maximum degradation of carcasses up to ca. 1.7 mg DW m−3 day−1 occurred in the density gradient zone of metalimnion. LOM released from zooplankton carcasses into the surrounding water may stimulate microbial activity and facilitate microbial degradation of more refractory organic matter; therefore, dead zooplankton are expected to be an integral part of water column carbon source/sink dynamics in stratified lakes.
Paternal diet induces transgenerational epigenetic inheritance of DNA methylation signatures and phenotypes in sheep model
Authors: Braz Camila U , Taylor Todd , Namous Hadjer , Townsend Jessica , Crenshaw Thomas , Khatib Hasan
Published: April 2022

Transgenerational epigenetic inheritance (TEI) requires transmission of environmentally induced epigenetic changes and associated phenotypes to subsequent generations without continued exposure to the environmental factor that originated the change. TEI is well-established in plants and Caenorhabditis elegans; however, occurrence in mammals is debated and poorly understood. Here, we examined whether paternal diet from weaning to puberty-induced changes in sperm DNA methylation that were transmitted to subsequent generations. Over 100 methylated cytosines, environmentally altered in the F0 generation, were inherited by the F1 and F2 generations. Furthermore, the F0 paternal diet was associated with growth and male fertility phenotypes in subsequent generations. Differentially methylated cytosines were correlated with gene expression. Our results demonstrate that some sperm methylation sites may escape DNA methylation erasure and are transmitted to subsequent generations despite the 2 waves of epigenetic programming: in primordial germ cells and in embryos after fertilization. These results advance our understanding of the complex relationships between nature and nurture.
‘Rails Invisibly Laid to Infinity’
Authors: Dodd Julian
Published: April 2022

This paper addresses what I call ‘the constitutive question’ concerning the rules we follow: namely, what determines the standard for a rule's correct application. John McDowell has offered a putative ‘middle position’ between two extreme, unacceptable answers: empirical idealism, which takes the requirements of a rule in any given situation to be constituted by our reaction to the case; and hard platonism, which takes these requirements to be delivered by unvarnished reality as absolutely the simplest or most natural way to carry on. Tellingly, however, McDowell's position is itself unacceptably idealist in his picture of the way in which we are ‘involved’ on the right-hand side of biconditionals such as, ‘“Diamonds are hard” is true if and only if diamonds are hard’.

In response to this stultifying state of affairs, I suggest that McDowell has followed the empirical idealist and hard platonist in assuming that the requirements of a rule must be grounded by something else: something external to the rule, which mediates between the rule and the standard for its correct application. This assumption is false. What is more, one application of a metaphor to which Wittgenstein has a somewhat equivocal relation—that of rules as rails invisibly laid to infinity—can help this point to stick.
Grit, Resilience, Mindset, and Academic Success in Physical Therapist Students: A Cross-Sectional, Multicenter Study
Authors: Calo Marlena , Judd Belinda , Chipchase Lucy , Blackstock Felicity , Peiris Casey L
Published: April 2022

Objective

The purpose of this study was to determine the relationships between noncognitive traits (grit, resilience, and mindset-type), academic success, and clinical performance in physical therapist students.

Methods

This cross-sectional study using self-administered surveys was undertaken with final-year physical therapist students enrolled in 4 Australian universities. Participants completed validated questionnaires measuring grit, resilience, and mindset type. Academic transcripts were obtained to quantify academic success and clinical performance. A multiple regression analysis explored predictors of academic success and clinical performance in relation to sociodemographic factors, grit, resilience, and mindset type.

Results

A total of 266 students participated in the study (80% recruitment rate). Overall, 25% of students had low resilience, 20% had low grit, and 14% had a fixed mindset type. Grittiness was positively associated with academic success (r = 0.24) and clinical performance (r = 0.22) and negatively associated with failing a clinical placement (r = -0.20). Grit was an independent predictor of overall academic success (β = 0.24, P ≤ .01) and clinical performance (β = 0.15). Students with low grit were twice as likely to fail a clinical placement compared with students with moderate or high grit (risk ratio = 2.03, 95% CI = 1.06 to 3.89).

Conclusion

Grit was an independent predictor for overall academic success and clinical performance in final-year physical therapist students. Low grit may impact negatively on learning and students’ ability to cope with challenges associated with university studies and clinical education. Further studies should investigate interventions that best develop grit in health professional students and the overlapping nature of grit, resilience, and a growth mindset.

Impact

This study helps universities and educators understand noncognitive factors predicting academic success and clinical performance in physical therapist students. Universities and clinical educators may consider screening and providing proactive strategies for students with low grit to improve success and general wellbeing.
Labor Market Returns and the Evolution of Cognitive Skills: Theory and Evidence
Authors: Hermo Santiago , Päällysaho Miika , Seim David , Shapiro Jesse M
Published: April 2022

A large literature in cognitive science studies the puzzling “Flynn effect” of rising fluid intelligence (reasoning skill) in rich countries. We develop an economic model in which a cohort’s mix of skills is determined by different skills’ relative returns in the labor market and by the technology for producing skills. We estimate the model using administrative data from Sweden. Combining data from exams taken at military enlistment with earnings records from the tax register, we document an increase in the relative labor market return to logical reasoning skill as compared to vocabulary knowledge. The estimated model implies that changes in labor market returns explain 37% of the measured increase in reasoning skill, and can also explain the decline in knowledge. An original survey of parents, an analysis of trends in school curricula, and an analysis of occupational characteristics show evidence of increasing emphasis on reasoning as compared to knowledge.
Whole blood drug levels do not correlate with QTc intervals in hydroxychloroquine-treated systemic lupus erythematosus patients
Authors: Belmont H Michael , Haj-Ali Mayce
Published: April 2022

Objectives

HCQ is recommended for all patients with SLE, but reports of cardiac toxicity in severe acute respiratory syndrome coronavirus 2 patients raised concerns. We aimed to study the relationship between HCQ blood levels and QTc intervals.

Methods

A retrospective review of 90 SLE patients (cohort 1) was conducted with data collected regarding demographics, QTc interval and chronic kidney disease (CKD). A prospective study of 84 SLE patients (cohort 2) was conducted with data collected regarding demographics, dose of HCQ, duration of HCQ treatment, presence of echocardiographic abnormalities and CKD simultaneous with whole blood HCQ levels measured by HPLC. Statistical analysis utilized one-way analysis of variance, Pearson’s correlation coefficient and t tests.

Results

In cohort 1 there was no significant difference in mean QTc based on 75 HCQ-treated [437.91 msec (s.d. 20.02)] as compared with 15 untreated patients [434.6 msec (s.d. 27.49)]. In patients with CKD, the mean QTc in HCQ users [448 (s.d. 23.37)] as compared with non-users [444.5 msec (s.d. 24.61)] also had no significant difference. In cohort 2, HCQ levels did not correlate with QTc interval (r = 0.017) and this applied regardless of the dose prescribed (r = 0.113 for 400 mg and r = 0.06 for 200 mg), duration of exposure (P = 0.36 for 0–5, >5–10 or >10 years), CKD (r = 0.482) or underlying cardiac abnormalities (r = 0.430).

Conclusions

This is the first study relying on measured blood levels demonstrating the absence of a clinically consequential increase in QTc levels in HCQ-treated SLE patients.
Cytokine profile, ferritin and multi-visceral involvement characterize macrophage activation syndrome during adult-onset Still’s disease
Authors: Ruscitti Piero , Ursini Francesco , Berardicurti Onorina , Masedu Francesco , Bozzalla Cassione Emanuele , Naldi Susanna , Di Cola Ilenia , Di Muzio Claudia , De Stefano Ludovico , Di Nino Elena , Navarini Luca , Vomero Marta , Bugatti Serena , Valenti Marco , Mariani Erminia , Iagnocco Annamaria , Montecucco Carlomaurizio , Giacomelli Roberto , Cipriani Paola
Published: April 2022

Objectives

To multidimensionally characterize macrophage activation syndrome (MAS) complicating adult-onset Still’s disease (AOSD) considering cytokine profile, inflammatory markers and multi-visceral involvement of the disease. To perform a high-dimensional phenotypic analysis of circulating immune cells in AOSD patients with and without MAS. To assess interferon (IFN)-related pathways in AOSD synovial tissues by a bulky RNA sequencing.

Methods

Clinical and biologic data were collected and compared in AOSD patients with and without MAS. Sera biomolecules were analysed by Luminex multiplexing technology. Mass cytometry (CyTOF) was used to characterize circulating immune cells. A bulky RNA sequencing was performed in AOSD synovial tissues.

Results

Forty consecutive AOSD patients were assessed, 14 complicated with MAS. Paralleling with increases of systemic score and ferritin, MAS patients showed higher levels of IL-1α, IL-1β, IL-1Ra, IL-2Ra, IL-6, IL-10, IL-17A, IFN-γ, G-CSF, MCP-1, MIP-1α and SCF. Combining the discriminatory ability of these data in identifying MAS, the best model was composed by systemic score, ferritin, IFN-γ and IL-10. By CyTOF analysis, MAS patients showed an increase of circulating ‘classical monocytes’ and a reduction of total NK cells. Our assessment showed 3477 IFN-related genes (IRGs) were differently expressed in AOSD synovial tissues.

Conclusions

A multidimensional characterization of AOSD patients suggested that IFN-γ, IL-10, ferritin and systemic score discriminated the occurrence of cytokine storm syndrome associated with MAS. The inflammatory milieu of AOSD and MAS may be related to a signature of circulating immune cells. Finally, our results about IRGs reinforced the role of IFN-γ in these patients.
Exploring discordance between Health Literacy Questionnaire scores of people with RMDs and assessment by treating health professionals
Authors: Bakker Mark M , Putrik Polina , Dikovec Cédric , Rademakers Jany , Vonkeman Harald E , Kok Marc R , Voorneveld-Nieuwenhuis Hanneke , Ramiro Sofia , de Wit Maarten , Buchbinder Rachelle , Batterham Roy , Osborne Richard H , Boonen Annelies
Published: April 2022

Objectives

We studied discordance between health literacy of people with rheumatic and musculoskeletal diseases (RMDs) and assessment of health literacy by their treating health professionals, and explored whether discordance is associated with the patients’ socioeconomic background.

Methods

Patients with RA, spondyloarthritis (SpA) or gout from three Dutch outpatient rheumatology clinics completed the nine-domain Health Literacy Questionnaire (HLQ). Treating health professionals assessed their patients on each HLQ domain. Discordance per domain was defined as a ≥2-point difference on a 0–10 scale (except if both scores were below three or above seven), leading to three categories: ‘negative discordance’ (i.e. professional scored lower), ‘probably the same’ or ‘positive discordance’ (i.e. professional scored higher). We used multivariable multilevel multinomial regression models with patients clustered by health professionals to test associations with socioeconomic factors (age, gender, education level, migration background, employment, disability for work, living alone).

Results

We observed considerable discordance (21–40% of patients) across HLQ domains. Most discordance occurred for ‘Critically appraising information’ (40.5%, domain 5). Comparatively, positive discordance occurred more frequently. Negative discordance was more frequently and strongly associated with socioeconomic factors, specifically lower education level and non-Western migration background (for five HLQ domains). Associations between socioeconomic factors and positive discordance were less consistent.

Conclusion

Frequent discordance between patients’ scores and professionals’ estimations indicates there may be hidden challenges in communication and care, which differ between socioeconomic groups. Successfully addressing patients’ health literacy needs cannot solely depend on health professionals’ estimations but will require measurement and dialogue.
Data versus Collateral
Authors: Gambacorta Leonardo , Huang Yiping , Li Zhenhua , Qiu Han , Chen Shu
Published: April 2022

Using a unique dataset of more than 2 million Chinese firms that received credit from both an important big tech firm (Ant Group) and traditional commercial banks, this paper investigates how different forms of credit correlate with local economic activity, house prices, and firm characteristics. We find that big tech credit does not correlate with local business conditions and house prices when controlling for demand factors, but reacts strongly to changes in firm characteristics, such as transaction volumes and network scores used to calculate firm credit ratings. By contrast, both secured and unsecured bank credit react significantly to local house prices, which incorporate useful information on the environment in which clients operate and on their creditworthiness. This evidence implies that the wider use of big tech credit could reduce the importance of the collateral channel but, at the same time, make lending more reactive to changes in firms’ business activity.
Maintenance Treatment With Antipsychotic Drugs in Schizophrenia: A Cochrane Systematic Review and Meta-analysis
Authors: Ceraso Anna , Lin Jessie Jingxia , Schneider-Thoma Johannes , Siafis Spyridon , Heres Stephan , Kissling Werner , Davis John M , Leucht Stefan
Published: April 2022

Antipsychotic drugs are the mainstay of treatment of schizophrenia, and are known to reduce acute symptoms of the disorder. An original version of the current review, published in 2012, examined whether antipsychotics are effective for relapse prevention, compared to withdrawing these agents for people with schizophrenia or schizophrenia-like psychoses, based on evidence from randomized trials. The current report of the update of the review is focused on some newly investigated outcomes: rates of remission and recovery, change in social functioning and in quality of life. The updated review included 75 randomized controlled trials (RCTs) published from 1959 to 2017, involving 9145 participants. Although some potential sources of bias limited the overall quality, the efficacy of antipsychotic drugs for maintenance treatment in schizophrenia was clear and robust to a series of sensitivity analyses. Antipsychotic drugs were more effective than placebo in preventing relapse at 1 year (drug 24% versus placebo 61%, 30 RCTs, n = 4249, RR = 0.38, 95% CI = 0.32 to 0.45) and in reducing hospitalization (drug 7% versus placebo 18%, 21 RCTs, n = 3558, RR = 0.43, 95% CI = 0.32 to 0.57). Quality of life appeared to be better in drug-treated participants (7 RCTs, n = 1573, SMD = −0.32, 95% CI = −0.57 to −0.07); the same for social functioning (15 RCTs, n = 3588, SMD = −0.43, 95% CI = −0.53 to −0.34). Although based on data from fewer studies, maintenance treatment apparently increased the possibility to achieve remission of symptoms (drug 53%, placebo 31%; 7 RCTs, 867 participants; RR = 1.73, 95% CI = 1.20 to 2.48) and to sustain it over 6 months (drug 36%, placebo 26%; 8 RCTs, 1807 participants; RR = 1.67, 95% CI = 1.28 to 2.19). There were no data on recovery. Antipsychotic drugs as a group were associated with more participants experiencing side effects such as movement disorders (e.g., at least one movement disorder: drug 14% versus placebo 8%, 29 RCTs, n = 5276, RR 1.52, 95% CI = 1.25 to 1.85) and weight gain (drug 9% versus placebo 6%, 19 RCTs, n = 4767, RR = 1.69, 95% CI = 1.21 to 2.35, NNTH = 25, 95% CI = 20 to 50). For people with schizophrenia, the evidence suggests that maintenance on antipsychotic drugs does not only prevent relapses and rehospitalizations, but that patients also benefit in terms of quality of life, functioning and sustained remission. These positive effects must be weighed against the backdrop of the adverse effects of antipsychotics.
An experimental investigation on the impact of wind turbine noise on polysomnography-measured and sleep diary-determined sleep outcomes
Authors: Liebich Tessa , Lack Leon , Hansen Kristy , Zajamsek Branko , Micic Gorica , Lechat Bastien , Dunbar Claire , Nguyen Duc Phuc , Scott Hannah , Catcheside Peter
Published: April 2022

Study Objectives

Carefully controlled studies of wind turbine noise (WTN) and sleep are lacking, despite anecdotal complaints from some residents in wind farm areas and known detrimental effects of other noises on sleep. This laboratory-based study investigated the impact of overnight WTN exposure on objective and self-reported sleep outcomes.

Methods

Sixty-eight participants (38 females) aged (mean ± SD) 49.2 ± 19.5 were recruited from four groups; N = 14, living <10 km from a wind farm and reporting WTN related sleep disruption; N = 18, living <10 km from a wind farm and reporting no WTN sleep disruption; N = 18, reporting road traffic noise-related sleep disruption; and N = 18 control participants living in a quiet rural area. All participants underwent in-laboratory polysomnography during four full-night noise exposure conditions in random order: a quiet control night (19 dB(A) background laboratory noise), continuous WTN (25 dB(A)) throughout the night; WTN (25 dB(A)) only during periods of established sleep; and WTN (25 dB(A)) only during periods of wake or light N1 sleep. Group, noise condition, and interaction effects on measures of sleep quantity and quality were examined via linear mixed model analyses.

Results

There were no significant noise condition or group-by-noise condition interaction effects on polysomnographic or sleep diary determined sleep outcomes (all ps > .05).

Conclusions

These results do not support that WTN at 25 dB(A) impacts sleep outcomes in participants with or without prior WTN exposure or self-reported habitual noise-related sleep disruption. These findings do not rule out effects at higher noise exposure levels or potential effects of WTN on more sensitive markers of sleep disruption.

Clinical Trial Registration

ACTRN12619000501145, UTN U1111-1229-6126. Establishing the physiological and sleep disruption characteristics of noise disturbances in sleep. https://www.anzctr.org.au/. This study was prospectively registered on the Australian and New Zealand Clinical Trial Registry.
Wnt5a Promotes AT1 and Represses AT2 Lineage-Specific Gene Expression in a Cell-Context-Dependent Manner
Authors: Li Changgong , Peinado Neil , Smith Susan M , Zhou Jing , Gao Feng , Kohbodi GoleNaz , Zhou Beiyun , Thornton Matthew E , Grubbs Brendan H , Lee Matt K , Bellusci Saverio , Borok Zea , Chen Ya-Wen , Minoo Parviz
Published: April 2022

Lung maturation is not limited to proper structural development but also includes differentiation and functionality of various highly specialized alveolar cell types. Alveolar type 1 (AT1s) cells occupy nearly 95% of the alveolar surface and are critical for establishing efficient gas exchange in the mature lung. AT1 cells arise from progenitors specified during the embryonic stage as well as alveolar epithelial progenitors expressing surfactant protein C (Sftpcpos cells) during postnatal and adult stages. Previously, we found that Wnt5a, a non-canonical Wnt ligand, is required for differentiation of AT1 cells during the saccular phase of lung development. To further investigate the role of Wnt5a in AT1 cell differentiation, we generated and characterized a conditional Wnt5a gain-of-function mouse model. Neonatal Wnt5a gain-of-function disrupted alveologenesis through inhibition of cell proliferation. In this setting Wnt5a downregulated β-catenin-dependent canonical Wnt signaling, repressed AT2 (anti-AT2) and promoted AT1 (pro-AT1) lineage-specific gene expression. In addition, we identified 2 subpopulations of Sftpchigh and Sftpclow alveolar epithelial cells. In Sftpclow cells, Wnt5a exhibits pro-AT1 and anti-AT2 effects, concurrent with inhibition of canonical Wnt signaling. Interestingly, in the Sftpchigh subpopulation, although increasing AT1 lineage-specific gene expression, Wnt5a gain-of-function did not change AT2 gene expression, nor inhibit canonical Wnt signaling. Using primary epithelial cells isolated from human fetal lungs, we demonstrate that this property of Wnt5a is evolutionarily conserved. Wnt5a therefore serves as a selective regulator that ensures proper AT1/AT2 balance in the developing lung.
Striving for Organizational Impact through Individual Impact: A Humanistic Management Approach Involving Social Work Supervisors
Authors: Zheng Guanghuai , Lyu Xinshu , Wang Yean
Published: April 2022

In today’s era of new public management, respecting the dignity and worth of social workers in organizational management poses a challenge to social work agencies. This research explores whether individual self-actualization can be integrated with organizational development by using a humanistic management approach. Authors sampled 672 supervisors from Chinese social work agencies. A structural equation model was built and tested to examine the relationships between four latent variables: (1) professional competence (PC), (2) organizational citizenship behaviors (OCBs), (3) individual impact, and (4) organizational impact, taking into account the moderating effect of professional associations. The results indicate that individual impact is a mediator between supervisors’ PC/OCBs and organizational impact. Meanwhile, professional associations play a moderating role in the relationship between supervisors’ PC and organizational impact. Findings provide the basis for a humanistic management strategy for social work agencies that focuses on the individual impact of key people to maximize organizational impact. Moreover, professional associations should strengthen the link between individual impact and organizational impact.