bluuebunny/crossref_metadata_2025 huggingface dataset:
Reporting characteristics of journal infographics: a cross-sectional study
Authors: Ferreira Giovanni E. , Elkins Mark R. , Jones Caitlin , O’Keeffe Mary , Cashin Aidan G. , Becerra Rosa E. , Gamble Andrew R. , Zadro Joshua R.
Published: April 2022

Background

Infographics have become an increasingly popular method to present research findings and increase the attention research receives. As many scientific journals now use infographics to boost the visibility and uptake of the research they publish, infographics have become an important tool for medical education. It is unknown whether such infographics convey the key characteristics that are needed to make useful interpretations of the data such as an adequate description of the study population, interventions, comparators and outcomes; methodological limitations; and numerical estimates of benefits and harms. This study described whether infographics published in peer-reviewed health and medical research journals contain key characteristics that are needed to make useful interpretations of clinical research.

Methods

In this cross-sectional study, we identified peer-reviewed journals listed in the top quintile of 35 unique fields of medicine and health research listed in the Journal Citation Reports database. Two researchers screened journals for the presence of infographics. We defined an infographic as a graphical visual representation of research findings. We extracted data from a sample of two of the most recent infographics from each journal. Outcomes were the proportion of infographics that reported key characteristics such as study population, interventions, comparators and outcomes, benefits, harms, effect estimates with measures of precision, between-group differences and conflicts of interest; acknowledged risk of bias, certainty of evidence and study limitations; and based their conclusions on the study’s primary outcome.

Results

We included 129 infographics from 69 journals. Most infographics described the population (81%), intervention (96%), comparator (91%) and outcomes (94%), but fewer contained enough information on the population (26%), intervention (45%), comparator (20%) and outcomes (55%) for those components of the study to be understood without referring to the main paper. Risk of bias was acknowledged in only 2% of infographics, and none of the 69 studies that had declared a conflict of interest disclosed it in the infographics.

Conclusions

Most infographics do not report sufficient information to allow readers to interpret study findings, including the study characteristics, results, and sources of bias. Our results can inform initiatives to improve the quality of the information presented in infographics.
Factors influencing bedtime procrastination in junior college nursing students: a cross-sectional study
Authors: Chen Dong , Zhang Yuhuan , Lin Jie , Pang Dong , Cheng Dongyang , Si Daiwei
Published: April 2022

Background

Sleep quality is related to physical and mental health. Though bedtime procrastination has been identified as a potentially key source of poor sleep quality, related research is scarce. The goal of our study was to determine bedtime procrastination among nursing students and identify its influencing factors.

Methods

This cross-sectional study comprised 1827 junior college nursing students. The data were collected from November to December 2021 using a mobile app-based survey. We evaluated demographic factors, Big Five personality traits, self-regulatory fatigue, future time perspective, and problematic mobile phone use. Multiple linear regression analysis was used to identify independent characteristics that influence bedtime procrastination among junior college nursing students.

Results

The mean bedtime procrastination score in junior college nursing students was 25.11 ± 6.88. Family monthly income of 3000–6000 RMB (β = 0.740; p = 0.015), as well as that of > 6000 RMB (β = 1.708; p = 0.001), and an extroverted personality (β = 0.225; p = 0.001), self-regulatory fatigue (β = 0.135; p < 0.001), and problematic mobile phone use (β = 0.078; p < 0.001) had significant positive effects on bedtime procrastination. Conscientious personality (β = − 0.284; p = 0.003), neurotic personality (β = − 0.203; p = 0.031), and future time perspective (β = − 0.141; p < 0.001) had significant negative effects on bedtime procrastination.

Conclusion

The nursing students who participated in this study had moderate levels of bedtime procrastination. Bedtime procrastination was predicted by higher monthly household income; personality traits of extroversion, conscientiousness, and neuroticism; self-regulatory fatigue; future time perspective; and problematic mobile phone use.

Practical implications

We recommend that effective measures are needed to help alleviate bedtime procrastination and improve the health and well-being of nursing students.
Evaluation of’the Buddy Study’, a peer support program for second victims in healthcare: a survey in two Danish hospital departments
Authors: Schrøder Katja , Bovil Tine , Jørgensen Jan Stener , Abrahamsen Charlotte
Published: April 2022

Background

Healthcare professionals involved in adverse events may suffer severe physical and emotional distress in the aftermath. Adequate support is critical to an overall culture of safety for any healthcare institution. This study evaluates a formalised peer support program, ‘the Buddy Study’, in two Danish university hospital departments. The program consists of a 2-h seminar about second victims and self-selected buddies to provide peer support after adverse events.

Methods

The study design involved a cross-sectional survey comprised of two close-ended questionnaires evaluating the Buddy Study seminar (Q1) and the Buddy Study program (Q2), along with two open-ended questions and three individual interviews for more elaborate answers.

Results

Out of the 250 HCPs employed in both departments, 191 midwives, physicians, and nursing assistants completed Q1 and 156 completed Q2. The seminars were evaluated positively; 91.6% were satisfied with the overall content of the seminar, and 69.1% agreed that insight into how other people may react to adverse events has helped them contain their own reactions or emotions. Assessments of having the Buddy Study program in the department or using or being used as a buddy were more diverse, yet overall positive. Three benefits of the program were identified: the program i) has encouraged an open and compassionate culture; ii) has caused attentiveness to the wellbeing of colleagues; and iii) the self-selected buddy relationship has created a safe space for sharing. Additionally, three challenges or shortcomings were identified: i) although peer support is valuable, it should not stand alone; ii) informal peer support is already in place, hence making a formalised system redundant; and iii) the buddy system requires continuous maintenance and visibility.

Conclusions

The overall evaluation of the Buddy Study program was positive, suggesting that this type of formalised peer support may contribute to a rapid and accessible second-victim support program in healthcare institutions. A key principle for the Buddy Study program is that relationships are crucial, and all buddy relationships are based on self-selection. This seems to offer a safe space for health care professionals to share emotional vulnerability and professional insecurity after an adverse event.
The effects of oclacitinib treatment on antimicrobial usage in allergic dogs in primary practice: an Australia wide case-control study
Authors: Rynhoud Hester , Croton Catriona , Henry Grace , Meler Erika , Gibson Justine S. , Soares Magalhaes Ricardo J.
Published: April 2022

Background

Canine allergic dermatitis is a common diagnosis in veterinary practices which can lead to secondary infections requiring treatment with antimicrobials. A previous study suggested that dogs treated with oclacitinib in an Australian referral hospital required fewer courses of antimicrobial therapy compared to dogs receiving other anti-pruritic treatments. This study aimed to quantify the effect of oclacitinib treatment on the use of antimicrobials and other therapies in general practice veterinary clinics across Australia. A retrospective case-controlled review of patient records was designed to investigate the number of courses of antimicrobials and other therapies in dogs that received oclacitinib (Apoquel®), compared with those who received an anti-pruritic treatment that was not oclacitinib.

Results

The target population included canine patients with a presumptive diagnosis of allergic dermatitis presenting between 2008 and 2018 to general practices contributing to the VetCompass Australia database. Patient records of interest were identified using search terms relating to allergic dermatitis, resulting in over 700,000 observations. Multivariable logistic regression models were developed to determine whether cases were prescribed fewer antimicrobial courses than controls, after adjusting for the presence of concurrent skin infections or infectious agents in ears. Our results indicate that fewer antimicrobial courses were prescribed in the cases compared to the controls. After adjusting for the concurrent skin infections, there was a significant reduction in the use of cefovecin [OR:0.62(0.39–0.98), P = 0.043], chlorhexidine [OR:0.57(0.42–0.77), P < 0.001], neomycin [OR:0.4(0.28–0.56), P < 0.001] and amoxycillin clavulanic acid (AMC) [OR: 0.55(0.39–0.78), P = 0.001] in cases compared to controls.

Conclusion

This study demonstrates a potential sparing effect of oclacitinib on the prescription of antimicrobials for the treatment of allergic skin diseases in dogs. This information may assist in the planning of treatment for canine allergic dermatitis, with consideration for antimicrobial stewardship.
The fciTABC and feoABI systems contribute to ferric citrate acquisition in Stenotrophomonas maltophilia
Authors: Liao Chun-Hsing , Lu Hsu-Feng , Huang Hsin-Hui , Chen Yu , Li Li-Hua , Lin Yi-Tsung , Yang Tsuey-Ching
Published: April 2022

Background

Stenotrophomonas maltophilia, a member of γ-proteobacteria, is a ubiquitous environmental bacterium that is recognized as an opportunistic nosocomial pathogen. FecABCD system contributes to ferric citrate acquisition inEscherichia coli. FeoABC system, consisting of an inner membrane transporter (FeoB) and two cytoplasmic proteins (FeoA and FeoC), is a well-known ferrous iron transporter system in γ-proteobacteria. As revealed by the sequenced genome,S. maltophiliaappears to be equipped with several iron acquisition systems; however, the understanding of these systems is limited. In this study, we aimed to elucidate the ferric citrate acquisition system ofS. maltophilia.

Methods

Candidate genes searching and function validation are the strategy for elucidating the genes involved in ferric citrate acquisition. The candidate genes responsible for ferric citrate acquisition were firstly selected using FecABCD ofE. colias a reference, and then revealed by transcriptome analysis ofS. maltophiliaKJ with and without 2,2′-dipyridyl (DIP) treatment. Function validation was carried out by deletion mutant construction and ferric citrate utilization assay. The bacterial adenylate cyclase two-hybrid system was used to verify intra-membrane protein–protein interaction.

Results

Smlt2858 and Smlt2356, the homologues of FecA and FecC/D ofE. coli, were first considered; however, deletion mutant construction and functional validation ruled out their involvement in ferric citrate acquisition.FciA(Smlt1148), revealed by its upregulation in DIP-treated KJ cells, was the outer membrane receptor for ferric citrate uptake. ThefciAgene is a member of thefciTABCoperon, in whichfciT, fciA,andfciCparticipated in ferric citrate acquisition. Uniquely, the Feo system ofS. maltophiliais composed of a cytoplasmic protein FeoA, an inner membrane transporter FeoB, and a predicted inner membrane protein FeoI. The intra-membrane protein–protein interaction between FeoB and FeoI may extend the substrate profile of FeoB to ferric citrate. FeoABI system functioned as an inner membrane transporter of ferric citrate.

Conclusions

The FciTABC and FeoABI systems contribute to ferric citrate acquisition inS. maltophilia.
Plasma phosphate and all-cause mortality in individuals with and without type 2 diabetes: the Dutch population-based lifelines cohort study
Authors: van der Vaart Amarens , Cai Qingqing , Nolte Ilja M. , van Beek André P. J. , Navis Gerjan , Bakker Stephan J. L. , van Dijk Peter R. , de Borst Martin H.
Published: April 2022

Introduction

Individuals with type 2 diabetes have a substantially elevated cardiovascular risk. A higher plasma phosphate level promotes vascular calcification, which may adversely affect outcomes in individuals with type 2 diabetes. We hypothesized that the association between plasma phosphate and all-cause mortality is stronger in individuals with type 2 diabetes, compared to those without diabetes.

Methods

We analysed the association between plasma phosphate and all-cause mortality in the Dutch population-based Lifelines cohort and in subgroups with and without type 2 diabetes, using multivariable Cox regression adjusted for potential confounders. Effect modification was tested using multiplicative interaction terms.

Results

We included 57,170 individuals with 9.4 [8.8–10.4] years follow-up. Individuals within the highest phosphate tertile (range 1.00–1.83 mmol/L) were at higher risk of all-cause mortality (fully adjusted HR 1.18 [95% CI 1.02–1.36], p = 0.02), compared with the intermediate tertile (range 0.85–0.99 mmol/L). We found significant effect modification by baseline type 2 diabetes status (p-interaction = 0.003). Within the type 2 diabetes subgroup (N = 1790), individuals within the highest plasma phosphate tertile had an increased mortality risk (HR 1.73 [95% CI 1.10–2.72], p = 0.02 vs intermediate tertile). In individuals without diabetes at baseline (N = 55,380), phosphate was not associated with mortality (HR 1.12 [95% CI 0.96–1.31], p = 0.14). Results were similar after excluding individuals with eGFR < 60 mL/min/1.73 m2.

Discussion

High-normal plasma phosphate levels were associated with all-cause mortality in individuals with type 2 diabetes. The association was weaker and non-significant in those without diabetes. Measurement of phosphate levels should be considered in type 2 diabetes; whether lowering phosphate levels can improve health outcomes in diabetes requires further study.
Cell type-specific response of colon cancer tumor cell lines to oncolytic HSV-1 virotherapy in hypoxia
Authors: Shayan Sara , Arashkia Arash , Bahramali Golnaz , Abdoli Asghar , Nosrati Mohammad Sadegh Shams , Azadmanesh Kayhan
Published: April 2022

Background

Novel strategies are required since the hypoxic tumor microenvironment is one of the important impediments for conventional cancer therapy. High mobility group box 1 (HMGB1) protein can block aerobic respiration in cancer cells. We hypothesized that HMGB1could also kill the colorectal cancer cells during hypoxia.

Methods

In this study, we developed oncolytic herpes simplex virus type 1 expressing HMGB1 protein (HSV-HMGB1) and investigated the cytotoxic effect of HSV-HMGB1 and its parental virus (HSV-ble) on three colorectal cancer cells (HCT116, SW480, and HT29) under normoxic (20% oxygen) and hypoxic (1% oxygen) conditions. We further identified potential autophagy- related genes in HT29 cells by retrieving mRNA expression microarray datasets from the Gene Expression Omnibus database. These genes were then detected in HT29 cells infected with HSV-HMGB1 and HSV-ble during normoxia and hypoxia by Real-Time quantitative PCR (qRT-PCR).

Results

The cytotoxic effect of HSV-HMGB1 was significantly higher than that of HSV-ble during normoxia; however, during hypoxia, HSV-HMGB1 enhanced the viability of HT29 cells at MOI 0.1. Analyzing the cell death pathway revealed that HSV-HMGB1 induced autophagy in HT29 cells under hypoxic conditions.

Conclusion

In conclusion, it appears that oncolytic virotherapy is cell context-dependent. Therefore, understanding the cancer cells’ characteristics, microenvironment, and cell signaling are essential to improve the therapeutic strategies.
Epidemic malaria dynamics in Ethiopia: the role of self-limiting, poverty, HIV, climate change and human population growth
Authors: Krsulovic Felipe Augusto Maurin , Moulton Timothy Peter , Lima Mauricio , Jaksic Fabian
Published: April 2022

Background

During the last two decades, researchers have suggested that the changes of malaria cases in African highlands were driven by climate change. Recently, a study claimed that the malaria cases (Plasmodium falciparum) in Oromia (Ethiopia) were related to minimum temperature. Critics highlighted that other variables could be involved in the dynamics of the malaria. The literature mentions that beyond climate change, trends in malaria cases could be involved with HIV, human population size, poverty, investments in health control programmes, among others.

Methods

Population ecologists have developed a simple framework, which helps to explore the contributions of endogenous (density-dependent) and exogenous processes on population dynamics. Both processes may operate to determine the dynamic behaviour of a particular population through time. Briefly, density-dependent (endogenous process) occurs when the per capita population growth rate (R) is determined by the previous population size. An exogenous process occurs when some variable affects another but is not affected by the changes it causes. This study explores the dynamics of malaria cases (Plasmodium falciparum and Plasmodium vivax) in Oromia region in Ethiopia and explores the interaction between minimum temperature, HIV, poverty, human population size and social instability.

Results

The results support that malaria dynamics showed signs of a negative endogenous process between R and malaria infectious class, and a weak evidence to support the climate change hypothesis.

Conclusion

Poverty, HIV, population size could interact to force malaria models parameters explaining the dynamics malaria observed at Ethiopia from 1985 to 2007.
Long noncoding RNA TLNC1 promotes the growth and metastasis of liver cancer via inhibition of p53 signaling
Authors: Yuan Kefei , Lan Jiang , Xu Lin , Feng Xuping , Liao Haotian , Xie Kunlin , Wu Hong , Zeng Yong
Published: April 2022

Background

Long non-coding RNAs (lncRNAs) have been demonstrated to play vital roles in cancer development and progression. However, their biological roles and function mechanisms in liver cancer remain largely unknown.

Methods

RNA-seq was performed with clinical hepatoma tissues and paired adjacent normal liver tissues to identify differentially expressed lncRNAs. qPCR was utilized to examine the expression levels of lncRNAs. We studied the function of TLNC1 in cell growth and metastasis of hepatoma with both cell and mouse models. RNA-seq, RNA pull-down coupled with mass spectrometry, RNA immunoprecipitation, dual luciferase reporter assay, and surface plasmon resonance analysis were used to analyze the functional mechanism of TLNC1.

Results

Based on the intersection of our own RNA-seq, TCGA RNA-seq, and TCGA survival analysis data, TLNC1 was identified as a potential tumorigenic lncRNA of liver cancer. TLNC1 significantly enhanced the growth and metastasis of hepatoma cells both in vitro and in vivo. TLNC1 exerted its tumorigenic function through interaction with TPR and inducing the TPR-mediated transportation of p53 from nucleus to cytoplasm, thus repressing the transcription of p53 target genes and finally contributing to the progression of liver cancer.

Conclusions

TLNC1 is a promising prognostic factor of liver cancer, and the TLNC1-TPR-p53 axis can serve as a potential therapeutic target for hepatoma treatment.
A critical review of definitions of rural areas in Indonesia and implications for health workforce policy and research
Authors: Putri Likke Prawidya , Russell Deborah Jane , O’Sullivan Belinda Gabrielle , Meliala Andreasta , Kippen Rebecca
Published: April 2022

Background

Choosing the appropriate definition of rural area is critical to ensuring health resources are carefully targeted to support the communities needing them most. This study aimed at reviewing various definitions and demonstrating how the application of different rural area definitions implies geographic doctor distribution to inform the development of a more fit-for-purpose rural area definition for health workforce research and policies.

Methods

We reviewed policy documents and literature to identify the rural area definitions in Indonesian health research and policies. First, we used the health policy triangle to critically summarize the contexts, contents, actors and process of developing the rural area definitions. Then, we compared each definition’s strengths and weaknesses according to the norms of appropriate rural area definitions (i.e. explicit, meaningful, replicable, quantifiable and objective, derived from high-quality data and not frequently changed; had on-the-ground validity and clear boundaries). Finally, we validated the application of each definition to describe geographic distribution of doctors by estimating doctor-to-population ratios and the Theil-L decomposition indices using each definition as the unit of analysis.

Results

Three definitions were identified, all applied at different levels of geographic areas: “urban/rural” villages (Central Bureau of Statistics [CBS] definition), “remote/non-remote” health facilities (Ministry of Health [MoH] definition) and “less/more developed” districts (presidential/regulated definition). The CBS and presidential definitions are objective and derived from nationwide standardized calculations on high-quality data, whereas the MoH definition is more subjective, as it allows local government to self-nominate the facilities to be classified as remote. The CBS and presidential definition criteria considered key population determinants for doctor availability, such as population density and economic capacity, as well as geographic accessibility. Analysis of national doctor data showed that remote, less developed and rural areas (according to the respective definitions) had lower doctor-to-population ratios than their counterparts. In all definitions, the Theil-L-within ranged from 76 to 98%, indicating that inequality of doctor density between these districts was attributed mainly to within-group rather than between-group differences. Between 2011 and 2018, Theil-L-within decreased when calculated using the MoH and presidential definitions, but increased when the CBS definition was used.

Conclusion

Comparing the content of off-the-shelf rural area definitions critically and how the distribution of health resource differs when analysed using different definitions is invaluable to inform the development of fit-for-purpose rural area definitions for future health policy.
Unusual presentation of primary ovarian diffuse large B-cell lymphoma: a case report
Authors: Luo Bin , He Rong-quan , Peng Zhi-gang , Ma Jie , Feng Zhen-bo , Chen Gang , Zeng Jing-jing
Published: April 2022

Background

Primary ovarian lymphoma has been difficult to diagnose clinically and pathologically due to its rare incidence and non-specific clinical symptoms.

Case presentation

A 75-year-old female patient was reported in this study. The patient had a six-month history of changes in bowel habits, with occasional black feces and paroxysmal pain in the abdomen. The computed tomography scan of the pelvic cavity illustrated that rectal cancer and sigmoid colon adenocarcinoma invaded the lower part of the right-side ureter. The patient was once treated with excision of part of small intestine, fallopian tube and ovary, and uterus. The pathological examination of these excised tissues, combined with the immunohistochemistry, confirmed that the female patient suffered from primary ovarian diffuse large B-cell lymphoma (DLBCL), and the lymphoma had invaded the entire right-side ovary tissues, serous membranes on the posterior surface of the uterus, and the wall of small intestine.

Conclusion

Few reports were available regarding the primary ovarian DLBCL. The initial symptom of the patient was the changes in bowel habits, which had not been reported beforehand. Hopefully, this case could helpfully render the early diagnosis possible, and increase clinical understanding of primary ovarian DLBCL, which would thereby reduce the chance of misdiagnosis.
Systemic sclerosis and pregnancy outcomes: a retrospective study from a single center
Authors: Barilaro Giuseppe , Castellanos Aleida , Gomez-Ferreira Inês , Lledó Gema Maria , Della Rocca Carlo , Fernandez-Blanco Lorena , Cervera Ricard , Baños Núria , Figueras Francesc , Espinosa Gerard
Published: April 2022

Background

Pregnancy in systemic sclerosis (SSc) patients is no more an infrequent event as it used to be, but literature data on pregnancy outcomes in women with SSc are scarce. The rate of preterm deliveries and intrauterine growth restriction (IUGR) seems to be increased, while the risk of miscarriages is controversial. Moreover, no study compared pregnancy outcomes in SSc with antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE). We performed a retrospective study to compare the pregnancy and disease outcomes of women with SSc with a cohort of age-matched women with systemic lupus erythematosus (SLE), antiphospholipid syndrome (APS), and healthy controls (HC).

Methods

A total of 154 pregnancies from SSc, SLE, APS patients, and HC were prospectively followed at the High-Risk Pregnancy Unit of our center from 2008 to 2019. The primary outcome was a composite endpoint of miscarriages, fetal deaths, intrauterine growth restriction (IUGR), preeclampsia, neonatal deaths, preterm birth, and small-for-gestational-age (SGA) newborns. Single adverse pregnancy outcomes (APO) represented secondary endpoints. SSc activity variations in relation to pregnancy were assessed.

Results

The risk of APO was significantly higher in SSc patients compared to HC (60.6% vs 10.0%; OR = 14.42; 95% CI 3.70–56.18, p = 0.001) and SLE patients (60.6% vs 37.5%; OR = 3.56; 95% CI 1.29–9.83, p = 0.014). Compared to HC, women with SSc had an increased frequency of first trimester miscarriage (15% vs 0 %; p = 0.016), preeclampsia (12% vs 0%, p = 0.038), and SGA newborns (21.2% vs 0%; p = 0.003). Preterm deliveries were more frequent in SSc pregnancies in comparison with HC (24.2% vs 5%; OR = 6.08; 95% CI 1.19–31.02, p = 0.036) and SLE patients (24.2% vs 7.5%, OR = 5.68; 95% CI 1.1–29.38, p = 0.038). Disease remained stable in all SSc patients during pregnancy and up to 1 year after delivery.

Conclusions

We found an increased risk of APO in our SSc cohort in comparison with HC (with higher rates of miscarriages, preeclampsia, SGA newborns, and preterm deliveries) and SLE patients (presenting a higher rate of preterm deliveries). High-risk multidisciplinary management of SSc pregnant women is highly recommended.
Software evaluation for de novo detection of transposons
Authors: Rodriguez Matias , Makałowski Wojciech
Published: April 2022

Transposable elements (TEs) are major genomic components in most eukaryotic genomes and play an important role in genome evolution. However, despite their relevance the identification of TEs is not an easy task and a number of tools were developed to tackle this problem. To better understand how they perform, we tested several widely used tools for de novo TE detection and compared their performance on both simulated data and well curated genomic sequences. As expected, tools that build TE-models performed better than k-mer counting ones, with RepeatModeler beating competitors in most datasets. However, there is a tendency for most tools to identify TE-regions in a fragmented manner and it is also frequent that small TEs or fragmented TEs are not detected. Consequently, the identification of TEs is still a challenging endeavor and it requires a significant manual curation by an experienced expert. The results will be helpful for identifying common issues associated with TE-annotation and for evaluating how comparable are the results obtained with different tools.
Technical considerations in PCR-based assay design for diagnostic DNA methylation cancer biomarkers
Authors: Massen Maartje , Lommen Kim , Wouters Kim A. D. , Vandersmissen Johan , van Criekinge Wim , Herman James G. , Melotte Veerle , Schouten Leo J. , van Engeland Manon , Smits Kim M.
Published: April 2022

Background

DNA methylation biomarkers for early detection, risk stratification and treatment response in cancer have been of great interest over the past decades. Nevertheless, clinical implementation of these biomarkers is limited, as only < 1% of the identified biomarkers is translated into a clinical or commercial setting. Technical factors such as a suboptimal genomic location of the assay and inefficient primer or probe design have been emphasized as important pitfalls in biomarker research. Here, we use eleven diagnostic DNA methylation biomarkers for colorectal cancer (ALX4,APC,CDKN2A,MGMT,MLH1,NDRG4,SDC2,SFRP1,SFRP2,TFPI1andVIM), previously described in a systematic literature search, to evaluate these pitfalls.

Results

To assess the genomic assay location, the optimal genomic locations according to TCGA data were extracted and compared to the genomic locations used in the published assays for all eleven biomarkers. In addition, all primers and probes were technically evaluated according to several criteria, based on literature and expert opinion. Both assay location and assay design quality varied widely among studies.

Conclusions

Large variation in both assay location and design hinders the development of future DNA methylation biomarkers as well as inter-study comparability.
Effects of stressful life-events on DNA methylation in panic disorder and major depressive disorder
Authors: Czamara Darina , Neufang Alexa , Dieterle Roman , Iurato Stella , Arloth Janine , Martins Jade , Ising Marcus , Binder Elisabeth E. , Erhardt Angelika
Published: April 2022

Background

Panic disorder (PD) is characterized by recurrent panic attacks and higher affection of women as compared to men. The lifetime prevalence of PD is about 2–3% in the general population leading to tremendous distress and disability. Etiologically, genetic and environmental factors, such as stress, contribute to the onset and relapse of PD. In the present study, we investigated epigenome-wide DNA methylation (DNAm) in respond to a cumulative, stress-weighted life events score (wLE) in patients with PD and its boundary to major depressive disorder (MDD), frequently co-occurring with symptoms of PD.

Methods

DNAm was assessed by the Illumina HumanMethylation450 BeadChip. In a meta-analytic approach, epigenome-wide DNAm changes in association with wLE were first analyzed in two PD cohorts (with a total sample size of 183 PD patients and 85 healthy controls) and lastly in 102 patients with MDD to identify possible overlapping and opposing effects of wLE on DNAm. Additionally, analysis of differentially methylated regions (DMRs) was conducted to identify regional clusters of association.

Results

Two CpG-sites presented with p-values below 1 × 10−05 in PD: cg09738429 (p = 6.40 × 10−06, located in an intergenic shore region in next proximity of PYROXD1) and cg03341655 (p = 8.14 × 10−06, located in the exonic region of GFOD2). The association of DNAm at cg03341655 and wLE could be replicated in the independent MDD case sample indicating a diagnosis independent effect. Genes mapping to the top hits were significantly upregulated in brain and top hits have been implicated in the metabolic system. Additionally, two significant DMRs were identified for PD only on chromosome 10 and 18, including CpG-sites which have been reported to be associated with anxiety and other psychiatric phenotypes.

Conclusion

This first DNAm analysis in PD reveals first evidence of small but significant DNAm changes in PD in association with cumulative stress-weighted life events. Most of the top associated CpG-sites are located in genes implicated in metabolic processes supporting the hypothesis that environmental stress contributes to health damaging changes by affecting a broad spectrum of systems in the body.
Predicting male fertility from the sperm methylome: application to 120 bulls with hundreds of artificial insemination records
Authors: Costes Valentin , Chaulot-Talmon Aurélie , Sellem Eli , Perrier Jean-Philippe , Aubert-Frambourg Anne , Jouneau Luc , Pontlevoy Charline , Hozé Chris , Fritz Sébastien , Boussaha Mekki , Le Danvic Chrystelle , Sanchez Marie-Pierre , Boichard Didier , Schibler Laurent , Jammes Hélène , Jaffrézic Florence , Kiefer Hélène
Published: April 2022

Background

Conflicting results regarding alterations to sperm DNA methylation in cases of spermatogenesis defects, male infertility and poor developmental outcomes have been reported in humans. Bulls used for artificial insemination represent a relevant model in this field, as the broad dissemination of bull semen considerably alleviates confounding factors and enables the precise assessment of male fertility. This study was therefore designed to assess the potential for sperm DNA methylation to predict bull fertility.

Results

A unique collection of 100 sperm samples was constituted by pooling 2–5 ejaculates per bull from 100 Montbéliarde bulls of comparable ages, assessed as fertile (n = 57) or subfertile (n = 43) based on non-return rates 56 days after insemination. The DNA methylation profiles of these samples were obtained using reduced representation bisulfite sequencing. After excluding putative sequence polymorphisms, 490 fertility-related differentially methylated cytosines (DMCs) were identified, most of which were hypermethylated in subfertile bulls. Interestingly, 46 genes targeted by DMCs are involved in embryonic and fetal development, sperm function and maturation, or have been related to fertility in genome-wide association studies; five of these were further analyzed by pyrosequencing. In order to evaluate the prognostic value of fertility-related DMCs, the sperm samples were split between training (n = 67) and testing (n = 33) sets. Using a Random Forest approach, a predictive model was built from the methylation values obtained on the training set. The predictive accuracy of this model was 72% on the testing set and 72% on individual ejaculates collected from an independent cohort of 20 bulls.

Conclusion

This study, conducted on the largest set of bull sperm samples so far examined in epigenetic analyses, demonstrated that the sperm methylome is a valuable source of male fertility biomarkers. The next challenge is to combine these results with other data on the same sperm samples in order to improve the quality of the model and better understand the interplay between DNA methylation and other molecular features in the regulation of fertility. This research may have potential applications in human medicine, where infertility affects the interaction between a male and a female, thus making it difficult to isolate the male factor.
Peptide hydrogel with self-healing and redox-responsive properties
Authors: D’Souza Areetha , Marshall Liam R. , Yoon Jennifer , Kulesha Alona , Edirisinghe Dona I. U. , Chandrasekaran Siddarth , Rathee Parth , Prabhakar Rajeev , Makhlynets Olga V.
Published: April 2022

We have rationally designed a peptide that assembles into a redox-responsive, antimicrobial metallohydrogel. The resulting self-healing material can be rapidly reduced by ascorbate under physiological conditions and demonstrates a remarkable 160-fold change in hydrogel stiffness upon reduction. We provide a computational model of the hydrogel, explaining why position of nitrogen in non-natural amino acid pyridyl-alanine results in drastically different gelation properties of peptides with metal ions. Given its antimicrobial and rheological properties, the newly designed hydrogel can be used for removable wound dressing application, addressing a major unmet need in clinical care.
Characterisation of ascocorynin biosynthesis in the purple jellydisc fungus Ascocoryne sarcoides
Authors: Wieder Carsten , Peres da Silva Roberta , Witts Jessica , Jäger Christof Martin , Geib Elena , Brock Matthias
Published: April 2022

Background

Non-ribosomal peptide synthetase-like (NRPS-like) enzymes are highly enriched in fungal genomes and can be discriminated into reducing and non-reducing enzymes. Non-reducing NRPS-like enzymes possess a C-terminal thioesterase domain that catalyses the condensation of two identical aromatic α-keto acids under the formation of enzyme-specific substrate-interconnecting core structures such as terphenylquinones, furanones, butyrolactones or dioxolanones. Ascocoryne sarcoides produces large quantities of ascocorynin, which structurally resembles a terphenylquinone produced from the condensation of p-hydroxyphenylpyruvate and phenylpyruvate. Since the parallel use of two different substrates by a non-reducing NRPS-like enzyme appeared as highly unusual, we investigated the biosynthesis of ascocorynin in A. sarcoides.

Results

Here, we searched the genome of A. sarcoides for genes coding for non-reducing NRPS-like enzymes. A single candidate gene was identified that was termed acyN. Heterologous gene expression confirmed that AcyN is involved in ascocorynin production but only produces the non-hydroxylated precursor polyporic acid. Although acyN is embedded in an ascocorynin biosynthesis gene cluster, a gene encoding a monooxygenase required for the hydroxylation of polyporic acid was not present. Expression analyses of all monooxygenase-encoding genes from A. sarcoides identified a single candidate that showed the same expression pattern as acyN. Accordingly, heterologous co-expression of acyN and the monooxygenase gene resulted in the production of ascocorynin. Structural modelling of the monooxygenase suggests that the hydrophobic substrate polyporic acid enters the monooxygenase from a membrane facing entry site and is converted into the more hydrophilic product ascocorynin, which prevents its re-entry for a second round of hydroxylation.

Conclusion

This study characterises the first naturally occurring polyporic acid synthetase from an ascomycete. It confirms the high substrate and product specificity of this non-reducing NRPS-like enzyme and highlights the requirement of a monooxygenase to produce the terphenylquinone ascocorynin.
Development of and reflections on ecological anthropology in China
Authors: Zeng Shaocong , Luo Yi
Published: April 2022

Ecological anthropology in China has a history of more than 70 years, and can be divided into four stages. The first stage was in the 1950s, which began with China’s identification of minzu and socio-historical surveys of ethnic minorities. This stage was characterized by refinement and application of the Economic-Cultural Type theory from Soviet ethnography. The second stage took place in the 1980s and 1990s, when China’s ecological anthropology research focused on explaining the relationship between local group culture and the environment, and how this changed in the process of modernization. Studies in this phase mainly concentrated on China’s southwestern and northwestern regions, and the theoretical trends of the “adaptation model” and “the cost of development” were formed, becoming central topics. The third stage was in the first decade of the twenty-first century, when Chinese ecological anthropologists focused on the natural and social consequences of changes in the ecological environment, and stressed the importance of exploring, protecting and transforming local ecological knowledge. Ecological anthropology research flourished in Hunan, Guizhou, and Guangxi as well as in the Daxing’anling and Xiaoxing’anling mountainous regions of Northeast China. The fourth stage was in the most recent decade, when ecological anthropologists expanded their research to cover disasters, biodiversity, local social vulnerability and promotion of ecological progress, and their research areas expanded to the southeastern coast, inland river basins and traditional farming areas in the Central Plains. This paper argues that the development of ecological anthropology in China has been driven by academic consciousness rooted in local field experience, accurate understanding of the research target and changes in social situations of the era, and in-depth dialogue with Western ecological anthropological theories. At present, China’s economic and social development patterns and the relationship between local people and their ecological environments are undergoing profound changes. Therefore, China’s ecological anthropology should respond and adapt to these new changes through solid ethnographic surveys, take root in local field experience, and draw on the wisdom of ecological civilization development in excellent traditional Chinese culture, to become aware of new theories and carry out innovative development.
Downhole microseismic data interpretation for media anisotropy evaluation with limited acquisition geometry in Western Siberia
Authors: Yaskevich Sergey Vladimirovich , Duchkov Anton A. , Kerusov Igor N. , Miroshnichenko Dmitriy E. , Loginov Georgy N.
Published: April 2022

We have evaluated the results of processing and interpretation for one of the first projects in Russia for downhole microseismic monitoring of hydraulic fracturing in Western Siberia. The data are characterized by large distance to the acquisition array and noisy recordings. We illustrate that preliminary quality control of microseismic array installation is a useful tool that may predict some of the issues and help to promote better acquisition quality. Therefore, it is important to reiterate the significance of the supervision for microseismic field measurements, especially when the technology is tested in new regions. Despite limited acquisition aperture and a comparatively small number of observed microseismic events, it is possible to derive valuable interpretation results from the data set. The geometry of the event locations suggests significant unplanned development of the hydraulic fractures, including a significant shift of the fracture from the initiation point. Records with clear S-wave splitting allowed us to determine arrival times of P waves and two S waves for several microseismic events. Arrival times were then used for simultaneous kinematic inversion for microseismic-event location and anisotropic velocity-model update (layered transversely isotropic with the vertical axis of symmetry model). We estimate significant anisotropy from microseismic data. Thomsen parameters [Formula: see text] and [Formula: see text] are well constrained, whereas parameter [Formula: see text] is constrained only for one of the layers.
Homologous Recombination Repair Gene Variants and Outcomes Among Patients With Prostate Cancer Treated With Poly (ADP-ribose) Polymerase Inhibitors
Authors: Price Meghan J. , Vashistha Vishal , Winski David , Kelley Michael J. , Bitting Rhonda L. , Montgomery Bruce
Published: April 2022

PURPOSE

Poly ADP-ribose polymerase inhibitors (PARPi) are used for patients with advanced prostate cancer bearing alterations in homologous recombination repair (HRR) genes. We sought to characterize HRR gene variants and describe real-world outcomes for patients on PARPi.

METHODS

The US Department of Veterans Affairs’ National Precision Oncology Program’s database was reviewed to identify patients who underwent somatic DNA sequencing and were prescribed a PARPi before May 15, 2020. Somatic and germline variants within HRR genes were reported, and pathogenicity was reviewed via OncoKB. In patients treated with PARPi for > 4 weeks, the rate of those achieving a 30% decrease in prostate-specific antigen (PSA30) and composite progression-free survival (PFS) were compared between patients bearing pathogenic variants of BRCA2 and patients without these variants using Mann-Whitney and log-rank tests, respectively.

RESULTS

Forty-eight patients bearing 67 total HRR gene variants were prescribed PARPi for prostate cancer. Twenty-one patients (43.8%) were found to have at least one pathogenic HRR gene variant. Eight (16.6%) were referred to genetic counseling, and five (10.4%) were ultimately confirmed with germline variants. The median PFS was 4.0 months, and PSA30 was 25.6% (11 of 43) for all 43 evaluable patients. Patients with pathogenic BRCA2 variants (n = 13) had higher PSA30 (69.2% v 4.0%; P < .001) and longer PFS (7.2 v 2.8 months; P = .0291) than those without.

CONCLUSION

In a real-world setting, heavily pretreated patients with prostate cancer and pathogenic BRCA2 variants have a significant PSA response rate and a PFS > 7 months with PARPi. This work emphasizes the importance of determining pathogenicity and origin of HRR alterations to better inform clinical treatment decisions and highlights the need for provider education and other decision support tools.
Remaking the Drunkard in Early Stuart England
Authors: Withington Phil
Published: April 2022

This article traces the changing semantics of drunkard in English during the first half of the seventeenth century. Combining methods of “distant reading” (made possible by the Early English Books Online–Text Creation Partnership) and the “close reading” of didactic printed materials, it shows how this venerable Middle English word became unusually prevalent and ideologically charged in the six decades after the ascension of James VI and I to the English throne. Key to these developments was the new monarch’s Counterblaste to Tobacco (1604), in which James I at once delineated a capacious concept of drunkard as someone who simply liked drinking, rather than became demonstrably drunk, and confirmed the consumption of tobacco and alcohol as an appropriate subject for the burgeoning printed “public sphere.” The article suggests that the separation of drunkard from drunkenness proved very useful for ministers and moralists concerned with the moral and economic consequences of unnecessary and “superfluous” consumption for individuals, households, and communities. Resorting to populist and didactic genres like pamphlets, sermons, dialogues, and treatises, writers ranging from the Calvinist John Downame to the regicide John Cook deployed the category of the drunkard to critique not only English drinking habits but also social and economic practices more generally. In pushing the concept so hard, however, reformers inevitably rubbed against more conventional notions of “civil society” and the sociable practices constituting it.
Nck adaptors at a glance
Authors: Bywaters Briana C. , Rivera Gonzalo M.
Published: April 2022

The non-catalytic region of tyrosine kinase (Nck) family of adaptors, consisting of Nck1 and Nck2, contributes to selectivity and specificity in the flow of cellular information by recruiting components of signaling networks. Known to play key roles in cytoskeletal remodeling, Nck adaptors modulate host cell–pathogen interactions, immune cell receptor activation, cell adhesion and motility, and intercellular junctions in kidney podocytes. Genetic inactivation of both members of the Nck family results in embryonic lethality; however, viability of mice lacking either one of these adaptors suggests partial functional redundancy. In this Cell Science at a Glance and the accompanying poster, we highlight the molecular organization and functions of the Nck family, focusing on key interactions and pathways, regulation of cellular processes, development, homeostasis and pathogenesis, as well as emerging and non-redundant functions of Nck1 compared to those of Nck2. This article thus aims to provide a timely perspective on the biology of Nck adaptors and their potential as therapeutic targets.