bluuebunny/crossref_metadata_2025 huggingface dataset:
DeepPHiC: Predicting promoter-centered chromatin interactions using a novel deep learning approach
Authors: Agarwal Aman , Chen Li
Published: May 2022

Motivation

Promoter-centered chromatin interactions, which include promoter-enhancer and promoter-promoter interactions, are important to decipher gene regulation and disease mechanisms. The development of next generation sequencing technologies such as promoter capture Hi-C (pcHi-C) leads to the discovery of promoter-centered chromatin interactions. However, pcHi-C experiments are expensive and thus may be unavailable for tissues or cell types of interest. In addition, these experiments may be underpowered due to insufficient sequencing depth or various artifacts, which results in a limited finding of interactions.

Results

To overcome these challenges, we develop a supervised multi-modal deep learning model, which utilizes a comprehensive set of features including genomic sequence, epigenetic signal and anchor distance to predict tissue/cell type-specific genome-wide promoter-enhancer and promoter-promoter interactions. We further extend the deep learning model in a multi-task learning and a transfer learning framework. We demonstrate that the proposed approach outperforms state-of-the-art deep learning methods and is robust to the inclusion of anchor distance as a feature. In addition, we find that the proposed approach can achieve comparable prediction performance using biologically relevant tissues/cell types compared to using all tissues/cell types especially for predicting promoter-enhancer interactions.

Availability

https://github.com/lichen-lab/DeepPHiC
plASgraph - using graph neural networks to detect plasmid contigs from an assembly graph
Authors: Sielemann Janik , Sielemann Katharina , Brejová Broňa , Vinař Tomáš , Chauve Cedric
Published: May 2022

Identification of plasmids from sequencing data is an important and challenging problem related to antimicrobial resistance spread and other One-Health issues. In our work, we provide a new architecture for identifying plasmid contigs in fragmented genome assemblies built from short-read data. Unlike previous machine-learning approaches for this problem, which classify individual contigs separately, we employ graph neural networks (GNNs) to include information from the assembly graph. Propagation of information from nearby nodes in the graph allows accurate classification of even short contigs that are difficult to classify based on sequence features or database searches alone.

Our new species-agnostic software tool plASgraph outperforms recently developed PlasForest, which uses database searches to supplement sequence-based features. Since our tool does not rely on existing plasmid databases, it is more suitable for classification of contigs in novel species and discovery of previously unknown plasmid sequences. Our tool can also be trained on a specific species, and in that scenario it outperforms mlplasmids trained on the same species.

On one hand, our work provides a new, accurate, and easy to use tool for plasmid classification; on the other hand, it serves as a motivation for more widespread use of GNNs in bioinformatics, such as in pangenome sequence analysis, where sequence graphs serve as a fundamental data structure.

Availability

https://github.com/cchauve/plASgraph
Weakly supervised identification of microscopic human breast cancer-related optical signatures from normal-appearing breast tissue
Authors: Shi Jindou , Tu Haohua , Park Jaena , Marjanovic Marina , Higham Anna M. , Luckey Natasha N. , Cradock Kimberly A. , Liu Z. George , Boppart Stephen A.
Published: May 2022

With the latest advancements in optical bioimaging, rich structural and functional information has been generated from biological samples, which calls for capable computational tools to identify patterns and uncover relationships between optical characteristics and various biomedical conditions. Constrained by the existing knowledge of the novel signals obtained by those bioimaging techniques, precise and accurate ground truth annotations can be difficult to obtain. Here we present a weakly supervised Deep Learning framework for optical signature discovery based on inexact and incomplete supervision. The framework consists of a Multiple Instance Learning-based classifier for the identification of regions of interest in coarsely labeled images, and model interpretation techniques for optical signature discovery. We applied this framework to investigate human breast cancer-related optical signatures based on virtual histopathology enabled by simultaneous label-free autofluorescence multiharmonic microscopy (SLAM), with the goal to explore unconventional cancer-related optical signatures from normal-appearing breast tissues. The framework has achieved an average area under the curve (AUC) of 0.975 on the cancer diagnosis task. In addition to well-known cancer biomarkers, non-obvious cancer-related patterns were revealed by the framework, including NAD(P)H-rich extracellular vesicles observed in normal-appearing breast cancer tissue, which facilitate new insights into the tumor microenvironment and field cancerization. This framework can be further extended to diverse imaging modalities and optical signature discovery tasks.
Rapid Loss of CD4 T Cells by Pyroptosis During Acute SIV Infection in Rhesus Macaques
Authors: He Xuan , Aid Malika , Ventura John D. , Borducchi Erica , Lifton Michelle , Liu Jinyan , Barouch Dan H.
Published: May 2022

The mechanisms underlying depletion of CD4 T cells during acute HIV-1 infection are not well understood. Here we show that caspase-1-induced pyroptosis, a highly inflammatory programmed cell death pathway, is the dominant mechanism responsible for the rapid depletion of CD4 T cells in gut-associated lymphatic tissue (GALT), spleen, and lymph nodes during acute simian immunodeficiency virus (SIV) infection in rhesus macaques. Upregulation of interferon-gamma inducible factor 16 (IFI16), a host DNA sensor that triggers pyroptosis, was also observed in tissue-resident CD4 T cells and correlated with viral loads and CD4 T cell loss. In contrast, caspase-3-mediated apoptosis and viral cytotoxicity only accounted for a small fraction of CD4 T cell death. Other programmed cell death mechanisms, including mitochondria-induced caspase-independent cell death, necroptosis, and autophagy, did not significantly contribute to CD4 T cell depletion. These data support a model in which caspase-1-mediated pyroptosis is the principal mechanism that results in CD4 T cell loss in the GALT and lymphoid organs and release of proinflammatory cytokines. These findings contribute to our understanding of the pathogenesis of acute SIV infection and have important implications for the development of therapeutic strategies.

Importance

Different mechanisms for CD4 T cell depletion during acute HIV-1 infection have been proposed. In this study, we should in SIV infected rhesus macaques that depletion of CD4 T cells is primarily due to pyroptosis. Other pathophysiologic mechanisms may also contribute in a minor way to CD4 T cell depletion.
Emergence and Genomic Characterization of Multidrug resistant Candida auris in West Africa
Authors: Oladele Rita , Uwanibe Jessica N. , Olawoye Idowu B. , Ettu Abdul-Wahab O. , Happi Christian T.
Published: May 2022

Candida auris is an emerging multidrug-resistant fungal pathogen that has become a worldwide public health threat due to limitations of treatment options, difficulty in diagnosis, and its potential for clonal transmission. Antifungal suceptibility tests and next generation sequencing were carried out on cultured isolates. Bioinformatics analysis was done using variant calling methods and genome-wide short nucleotide polymorphism (SNP) based phylogeny. Here, we report the first four cases of C. auris infection and colonization reported in West Africa. A total of four isolates from four reported cases of candidemia were analyzed. Three patients had fungaemia, which led to fatal invasive infection and the last patient was a likely case of colonization. Of the four patients, two had mutations which conferred resistance to the antifungal azole group and other non-synonymous mutations in hotspot genes such as ERG2, ERG11 and FKS1. Isolates from these patients clustered to clades I and IV, which indicates more than one introduction of C.auris into Nigeria. The first report of C. auris in Nigeria and West Africa is of public health importance as this report will aid identification, surveillance and intervention of resistant drug resistant candidiasis in the region.
Unique role for lncRNA HOTAIR in defining depot-specific gene expression patterns in human adipose-derived stem cells
Authors: Erdos Edina , Divoux Adeline , Sandor Katalin , Halasz Laszlo , Smith Steven R. , Osborne Timothy F.
Published: May 2022

Accumulation of fat above the waist is an important risk factor in developing obesity-related comorbidities independently of BMI or total fat mass. Deciphering the gene regulatory programs of the adipose tissue precursor cells within upper body or abdominal (ABD) and lower body or gluteofemoral (GF) depots is important to understand their differential capacity for lipid accumulation, maturation, and disease risk. Previous studies identified the HOX transcript antisense intergenic RNA (HOTAIR) as a GF-specific lncRNA; however, its role in adipose tissue biology is still unclear. Using three different approaches (silencing of HOTAIR in GF human adipose-derived stem cells [GF hASCs], overexpression of HOTAIR in ABD hASCs, and ChIRP-seq) to localize HOTAIR binding in GF hASC chromatin, we found that HOTAIR binds and modulates expression, both positively and negatively, of genes involved in adipose tissue-specific pathways, including adipogenesis. We further demonstrate a direct interaction between HOTAIR and genes with high RNAPII binding in their gene bodies, especially at their 3′ ends or transcription end sites. Computational analysis suggests HOTAIR binds preferentially to the 3′ ends of genes containing predicted strong RNA–RNA interactions with HOTAIR. Together, these results reveal a unique function for HOTAIR in hASC depot-specific regulation of gene expression.
The Inner Shell Spectroscopy beamline at NSLS-II: a facility for in situ and operando X-ray absorption spectroscopy for materials research
Authors: Leshchev Denis , Rakitin Maksim , Luvizotto Bruno , Kadyrov Ruslan , Ravel Bruce , Attenkofer Klaus , Stavitski Eli
Published: May 2022

The Inner Shell Spectroscopy (ISS) beamline on the 8-ID station at the National Synchrotron Light Source II (NSLS-II), Upton, NY, USA, is a high-throughput X-ray absorption spectroscopy beamline designed for in situ, operando, and time-resolved material characterization using high monochromatic flux and scanning speed. This contribution discusses the technical specifications of the beamline in terms of optics, heat load management, monochromator motion control, and data acquisition and processing. Results of the beamline tests demonstrating the quality of the data obtainable on the instrument, possible energy scanning speeds, as well as long-term beamline stability are shown. The ability to directly control the monochromator trajectory to define the acquisition time for each spectral region is highlighted. Examples of studies performed on the beamline are presented. The paper is concluded with a brief outlook for future developments.
Crystal structure and Hirshfeld surface analysis of 2,4,6-triaminopyrimidine-1,3-diium dinitrate
Authors: Dilshad Sumra , Çınar Emine Berrin , Ali Arif , Ahmed Adeeba , Alam Mohd Jane , Ahmad Musheer , Ahmad Aiman , Dege Necmi , Saif Eiad
Published: May 2022

The title compound, C4H9N5
2+·2NO3
−, crystallizes in the monoclinic crystal system, space group P21/c. The asymmetric unit, which comprises a diprotonated triaminopyrimidine dication and two nitrate anions, has an almost planar geometry with a dihedral angle of 0.92 (4)° between the mean plane of the cation and that defined by both anions. In the crystal, hydrogen-bonding interactions between the 2,4,6-triaminopyrimidine cation and the nitrate anions lead to a one-dimensional supramolecular network with weak anionic interactions forming a three-dimensional network. These interactions were investigated using Hirshfeld surface analysis, which indicates that the most important contributions for the packing arrangement are from O...H/H...O (53.2%), N...H/H...N (12.5%) and C...H/H...C (9.6%) interactions. Energy framework analysis showed that of the components of the framework energies, electrostatic repulsion (E
rep) is dominant.
Causes of workplace violence against medical staff as perceived by physicians and nurses in Jordanian public hospitals
Authors: Shiyab Ahmad , Ababneh Raed Ismail , Shyyab Yaser
Published: May 2022

Purpose

Workplace violence against medical staff has become an endemic problem in the healthcare sector in Jordan. This study investigates the perceived main causes of workplace violence (medical staff, administrative, patients, patient's escorts and legislative) against physicians and nurses in public hospitals.

Design/methodology/approach

A self-administered questionnaire was used to collect data from a convenient random sample of 334 physicians and nurses employed in Jordanian public hospitals. Descriptive statistics and analysis of variance were used to answer questions and test hypotheses.

Findings

Findings indicated that the practice of the causes of workplace violence behaviors assessed by the participants is at a moderate level in Jordanian public hospitals with a mean value of 3.26. The causes of violence were reported as most causative to least causative: patient escort (M = 3.60), legislative (M = 3.56), patients (M = 3.40), administrative (M = 3.16) and medical staff related (M = 2.74), respectively. Analysis showed statistical differences in the participants' attitudes toward the causes of workplace violence behaviors due to their gender, job title, education level, experience and income.

Practical implications

This study has a significant practical contribution in providing information about the causes of workplace violence that will help health policymakers and hospital administrators to deter violence against medical staff. To reduce or eliminate the potential causes of violence, several actions can be taken, such as criminalizing violent behaviors, managing work pressure, staff shortages, developing comfortable and secure medical treatment settings, training the medical staff on aggression and stress management, and enhancing their communication skills with patients and their escorts. Findings also highlight the need for hospital management to develop protocols for reporting and dealing with workplace violence.

Originality/value

This is one of the first studies in the Arab context that examines the causes of workplace violence against medical staff.
The role of environmental management accounting and environmental knowledge management practices influence on environmental performance: mediated-moderated model
Authors: Bresciani Stefano , Rehman Shafique Ur , Giovando Guido , Alam Gazi Mahabubul
Published: May 2022

Purpose

This study aims to observe the influence of environmental management accounting (EMA) and environmental knowledge management (KM) practices on environmental performance with mediating role of top management support (TMS). Moreover, green work climate perception (GWCP) is used as a moderator between TMS and environmental performance.

Design/methodology/approach

Partial least square-structural equation modeling is used to test research hypotheses. Data was collected to distribute questionnaires in light of the purposive sampling technique; a total of 329 questionnaires were used for final analysis. This study is correlational and cross-sectional. Multiple regression analysis was used to see the influence of EMA, environmental KM practices, TMS and GWCP on environmental performance.

Findings

The results reveal that EMA, environmental KM practices and TMS are positively related to environmental performance. Moreover, TMS significantly mediates between EMA, environmental KM practices and environmental performance. GWCP is positively associated with environmental performance. Finally, GWCP significantly strengthens the positive relationship between TMS and environmental performance.

Practical implications

This study highlighted a significant issue that of how top management uses EMA, environmental KM practices, TMS and GWCP in examining environmental performance. Moreover, this study covers the gap and supports top management to concentrate on exogenous variables to examine environmental performance.

Originality/value

This study adds value to literature to focus on factors that influence environmental performance. This initial research observes the influence of EMA and environmental KM practices on environmental performance with TMS as a mediator in light of the knowledge-based view. Besides, GWCP is used as a moderator between TMS and environmental performance. Finally, our research can provide benefits to researchers, students and managers.
Preparing educators who save lives: what can US schools of education do?
Authors: Harushimana Immaculee
Published: May 2022

Purpose

Aided with critical-race theory (Ladson-Billings, 1998), culturally responsive pedagogy tenets (Gay, 2002), and culturally sustaining pedagogy philosophy (Paris, 2012). The purpose of this paper is to make a two-pronged argument that: the killing of blacks has taken many forms, physical, moral, intellectual, cultural, and financial; and through its endorsement of racist policies, the education domain is a covert partaker in the killing of black lives. The author proceeds to tell her story of how lived experience, i.e., related to racism and inequities, inspired her to implement a curriculum that saves lives. She then proposes actionable measures that leaders of schools of education can take to show that they are allies of anti-black-racism and racial equity voices in education.

Design/methodology/approach

Methodologically, this paper is situated in the intersection of three methodological models, which share the use of narrative as a source of evidence: critical participatory action research, critical autoethnography and narrative inquiry.

Findings

The author’s narrative of lived experience, demonstrates the difficulty of black faculty of education to prepare nonblack educators who save black children’s lives and the author’s determination to tailor her syllabus to that urgent goal.

Originality/value

This study is one of its kind in claiming that ill-prepared teachers can “kill lives” and advocating that “saving lives” should be the mission of teacher preparation programs, especially those in high-diversity urban schools.
Processes underpinning survival in gay men living with HIV and a history of suicidality
Authors: Handlovsky Ingrid , Ferlatte Olivier , Kia Hannah , Knight Rod , Broom Alex , Oliffe John
Published: May 2022

Gay men living with HIV represent a particularly high risk group for suicide; however, little is known about suicidality, specifically, resiliencies in the context of suicidality among this particular group of men. The current study draws on photovoice and grounded theory methods to examine the processes that underpin survival for gay men living with HIV who have experienced suicidality. Twenty‐two Canadian‐based gay men participated, taking photographs to depict and discuss their perspectives on resiliencies. Analyses revealed three processes that supported men's survival: (1) connecting to key supports, (2) finding sanctity in the outdoors, and (3) giving help as purposeful value‐adding. Connecting to key supports highlighted the utility of connection and therapeutic communication, listening and support provided by friends, family and professionals. Finding sanctity in the outdoors emphasised the healing capacity of outdoor green spaces, and giving help as purposeful value‐adding illustrated the meaning and purpose men derived from supporting others. These findings can inform public health and primary care interventions to foster gay men's resilience and coping, and ultimately suicide prevention efforts.
Follow‐up frequency and clinical outcomes in patients with type 2 diabetes: A prospective analysis based on multicenter real‐world data
Authors: Zhao Qiubo , Li Hongwei , Ni Qicheng , Dai Yuancheng , Zheng Qidong , Wang Yufan , Ke Tingyu , Li Li , Zhao Dong , Dong Qijuan , Ji Bangqun , Shi Juan , Peng Ying , Zhang Yifei , Xu Fengmei , Wang Weiqing
Published: May 2022

Background

To determine whether the follow‐up frequency for type 2 diabetes mellitus (T2DM) patients in the National Metabolic Management Centers (MMCs) leads to different clinical outcomes.

Methods

A total of 19 908 T2DM patients with at least 6 months of facility‐based follow‐up were recruited in MMCs between June 2017 and April 2021 and divided into lower‐frequency and higher‐frequency follow‐up (LFF and HFF) groups according to the median follow‐up frequency of 2.0 (interquartile range 1.2) times per year. Metabolic parameters at baseline and at the last follow‐up visit were analyzed. Multivariable linear regression models were performed to assess the relationship between follow‐up frequency and between‐group percentage changes, adjusting for the major covariables. Additional stratified analyses were conducted to evaluate the metabolic outcomes in the subgroups.

Results

The characteristics of the participants in the LFF and HFF groups were significantly different at baseline. Participants had significant improvements in multiple metabolic parameters after follow‐up. Patients with HFF showed significantly greater decrease in percentage changes of fasting blood glucose (−4.95% ± 37.96% vs −2.21% ± 43.08%, P < .0001) and glycosylated hemoglobin (HbA1c) (−12.14% ± 19.78% vs −9.67% ± 20.29%, P < .0001) after adjustments compared to those with LFF. Furthermore, stratification analyses showed that significant between‐group percentage changes of HbA1c were observed in those with younger age (<55 years) and higher HbA1c (>9%) at baseline (P for interaction <.001).

Conclusions

HFF is associated with better metabolic outcomes. Participants, especially with younger age or worse HbA1c at baseline in the HFF group achieved better glycemic control than those in the LFF group.
Remission of peanut allergy is associated with rewiring of allergen‐driven T helper 2‐related gene networks
Authors: Ashley Sarah E. , Jones Anya C. , Anderson Denise , Holt Patrick G. , Bosco Anthony , Tang Mimi L. K.
Published: May 2022

Background

The immunological changes underpinning acquisition of remission (also called sustained unresponsiveness) following food immunotherapy remain poorly defined. Limited access to effective therapies and biosamples from treatment responders has prevented progress. Probiotic peanut oral immunotherapy is highly effective at inducing remission, providing an opportunity to investigate immune changes.

Methods

Using a systems biology approach, we examined gene co‐expression network patterns in peanut‐specific CD4+ T cell responses before and after probiotic and peanut oral immunotherapy in subjects enrolled in the PPOIT‐001 randomized trial: Responders who attained remission (n = 16), placebo‐treated who remained allergic (n = 16).

Results

Acquisition of remission was associated with rewiring of gene network patterns, which was characterized by integration of T helper 2 and interferon signalling modules, markedly reduced T helper 2 gene connectivity, and shutdown in co‐expression activity between T helper 2 effectors and cell cycle regulators.

Conclusion

The immunological changes underlying remission following peanut oral immunotherapy are mediated by reprogramming of T helper 2‐associated gene networks in the CD4+ T cell compartment. Findings provide insight into immune mechanisms driving the acquisition of remission following oral immunotherapy, paving the way for the development of improved approaches to induce remission/sustained unresponsiveness in patients with food allergy.
PD‐L1 expression and FGFR‐mutations among Danish patients diagnosed with metastatic urothelial carcinoma: A retrospective and descriptive study
Authors: Grantzau Trine , Toft Birgitte Grønkær , Melchior Linea Cecilie , Elversang Johanna , Stormoen Dag Rune , Omland Lise Høj , Pappot Helle
Published: May 2022

Checkpoint inhibitors have changed the treatment landscape of advanced urothelial carcinoma (mUC), and recently, a fibroblast‐growth‐factor‐receptor (FGFR) inhibitor has been introduced. This study aimed at estimating programmed death‐ligand 1 (PD‐L1) expression in primary tumors (PTs) and the PD‐L1 expression concordance between PTs and paired metastases in 100 patients with UC managed in the real‐world setting. Further, the aim was to investigate FGFR1–3 aberrations and the correlation between FGFR1–3 aberrations and PD‐L1 expression. PD‐L1 immunohistochemistry was performed on 100 formalin‐fixed paraffin‐embedded archival primary UC samples and 55 matched metastases using the 22C3 PD‐L1 assay. PD‐L1 expression was determined by the combined positive score, considered positive at ≥10. Targeted next‐generation sequencing on the S5+/Prime System with the Oncomine Comprehensive Assay version 3 was used to detect FGFR1‐3 aberrations in PTs. We found that 29 of 100 PTs had positive PD‐L1 expression. The PD‐L1 concordance rate was 71%. FGFR1‐3 aberrations were observed in 18% of PTs, most frequently FGFR3 amplifications or mutations. We found no association between FGFR1‐3 aberrations and PT PD‐L1 expression (p = 0.379). Our data emphasize the need for further studies in predictive biomarkers.
Elective cricothyrotomy in a dog with transient laryngeal paralysis secondary to Australian paralysis tick (Ixodes holocyclus) envenomation
Authors: Hardjo S , Nash KJ , Day SK , Haworth MD
Published: May 2022

The tube cricothyrotomy (CTT) has recently been introduced to small animal medicine as a viable surgical airway access procedure; however, there are no reports documenting its clinical use. The author's objective is to describe the clinical application, complications, and management of an elective CTT in a dog. Furthermore, the characteristics of CTT that may be clinically advantageous over temporary tube tracheostomy (TT) will be discussed. A 2‐year‐old female spayed German shepherd dog required mechanical ventilation (MV) due to unsustainable work of breathing as a result of tick paralysis and aspiration pneumonia. After successful weaning from MV, the dog was diagnosed with laryngeal paralysis. A surgical airway was performed using CTT to allow extubation and patient management whilst conscious. Complications included frequent tube suctioning due to accumulation of airway secretions in the tube and a single dislodgement event. The dog made an uneventful recovery with complete stoma healing by the second intention within 15 days. To the authors' knowledge, this is the first clinical report of an elective CTT performed to successfully manage upper airway obstruction in the dog. Its efficacy, clinical management and patient outcome are described.
Development, preliminary validation and reliability of the colourful ‘My Feelings Form’ self‐report for young children
Authors: Mulligan Aisling , Sresthaporn Natthaphol , Mulroy Sinead , Rudd Tara , Coffey Anne , Joyce Maria , Gadancheva Veselina , Glancy Caoimhe
Published: May 2022

Background

Patient‐reported outcome measures place the patient at the centre of his/her care. There are calls to introduce child‐reported outcome measures to mental health services. We aimed to (a) develop an age‐appropriate patient‐reported outcome measure for children's mental health, and (b) validate this in a primary school and Child and Adolescent Mental Health Service (CAMHS).

Methods

A list of items to measure children's mental health was proposed (Draft 1) and revised to 14 items following focus group and user consultation (Draft 2). A colourful, cartoon and emoji version was created in consultation with children (Draft 3); a professional cartoon artist created the final ‘My Feelings Form’ (MFF), with usability feedback (Draft 4). The MFF was tested by 317 children aged 4–13 years from one mixed‐gender primary school at two time points in 1 day, and 25 children aged 4–13 years from CAMHS. Results were analysed using test–retest reliability and exploratory factor analysis; a receiver operator characteristic curve was constructed.

Results

The CAMHS group scored significantly higher than the school group for the mean total score (23.5 ± 11.3 vs. 16.1 ± 6.2) and for 10 items. Test–retest reliability was acceptable (correlation = 0.74, p < .001). Exploratory factor analysis using 10 informative items identified two factors – emotional factor (Cronbach's alpha = 0.74) and function factor (Cronbach's alpha = 0.59). The revised 10‐item form has a Cronbach's alpha of 0.77; a cut‐off of 12 has a sensitivity of 80% and specificity of 60%, indicating that it correctly identified 80% of those who were attending CAMHS and gave 60% of the schoolchildren a negative result.

Conclusions

The colourful MFF was co‐produced with children, and preliminary data suggest that it is a useful patient‐reported outcome measure for children's mental health.
Do Norwegian private dental practitioners with too few patients compensate for their loss of income by providing more services or by raising their fees?
Authors: Grytten Jostein , Listl Stefan , Skau Irene
Published: May 2022

Objective

In Norway, supply of dental services exceeds demand, mainly because of the marked improvement in dental health during the last few decades. The aim of the study was to investigate whether private dental practitioners counteract a fall in demand for their services by providing more services or by raising their fees.

Methods

The data were collected using a questionnaire that was sent to all private dental practitioners in Norway. Altogether 1237 practitioners responded, which gave a response rate of 56%. Our sample was representative of the population of practitioners in Norway. As a measure of patient supply, responses from the following questions were used: ‘Based on an overall assessment of economy, workload and other personal factors, is the number of regular patients adequate? If not, do you wish to have more patients, or fewer patients?’ The outcome variables were dental fees, length of recall interval and mean cost per visit. The data were analysed using ordinary least square regression and a linear probability model. The following characteristics of the private dental practitioners were included as control variables: age, gender, work experience in years and whether they worked in a solo practice. To test the robustness of the findings, a supplementary analysis with the patient as the unit of analysis was carried out, using survey data of Norwegians aged 20 years and older. Based on this survey, the relationship between population: dentist ratio and mean cost per dental visit were examined.

Results

Nearly 40% of all practitioners reported that they had too few patients. They compensated for their loss of income by raising their fees, by recalling their patients more often and by increasing the cost per visit. The finding in the supplementary analysis using survey data from patients was similar to the findings in the main analyses using survey data from private dental practitioners.

Conclusion

The findings show that practitioners have market power. They were able to counteract a fall in demand for their services by providing more services and by raising their fees. The dental profession should be encouraged to provide appropriate services, in the present situation where supply exceeds demand.
Role of renin–angiotensin–aldosterone system activation and other metabolic variables in relation to arterial inflammation in HIV
Authors: Shen Grace , Thomas Teressa S. , Walpert Allie R. , McClure Colin M. , Fitch Kathleen V. , deFilippi Christopher , Torriani Martin , Buckless Colleen G. , Adler Gail K. , Grinspoon Steven K. , Srinivasa Suman
Published: May 2022

Background

Arterial inflammation remains increased among persons with HIV (PWH) compared with persons without HIV (PWOH) even when controlling for traditional risk factors. We sought to understand whether increased renin–angiotensin–aldosterone system (RAAS) activation may be related to arterial inflammation in PWH and when compared with PWOH.

Design

Twenty PWH and 9 PWOH followed a controlled, standardized low and liberal sodium diet to simulate a RAAS‐activated and RAAS‐suppressed state, respectively. We measured serum lipoprotein‐associated phospholipase A2 (LpPLA2) concentrations following both conditions to assess the physiologic dynamics of aldosterone in relation to arterial inflammation.

Results

LpPLA2 levels were significantly higher among PWH versus PWOH during both the RAAS‐activated state[5.3(4.2, 6.1) versus 4.0(3.0, 4.8)nmol/L, median(interquartile range),p = .01]) and RAAS‐suppressed state[4.4(3.9, 5.3) versus 3.8(3.4, 4.1)nmol/L,p = .01]. Among PWH, but not PWOH, LpPLA2 increased significantly with RAAS activation(p = .03). LpPLA2 levels measured during the RAAS‐suppressed state among PWH remained relatively higher than LpPLA2 levels under both conditions among PWOH. Log LpPLA2 was related to log aldosterone during the RAAS‐activated state(r = .39,p = .04) among all participants. Log LpPLA2 was correlated with visceral fat(r = .46,p = .04) and log systolic blood pressure(r = .57,p = .009) during a RAAS‐activated state when an increase in aldosterone was stimulated in HIV.

Conclusion

LpPLA2 is increased during a RAAS‐activated state among PWH, but not among PWOH. Further, LpPLA2 was increased in both RAAS‐activated and suppressed states in PWH compared with PWOH. These data suggest a biological link between increased aldosterone and arterial inflammation in this population. Future studies should test RAAS blockade on arterial inflammation as a targeted treatment approach in HIV.
Biallelic variants in ZNF142 lead to a syndromic neurodevelopmental disorder
Authors: Christensen Maria B. , Levy Amanda M. , Mohammadi Nazanin A. , Niceta Marcello , Kaiyrzhanov Rauan , Dentici Maria Lisa , Al Alam Chadi , Alesi Viola , Benoit Valérie , Bhatia Kailash P. , Bierhals Tatjana , Boßelmann Christian M. , Buratti Julien , Callewaert Bert , Ceulemans Berten , Charles Perrine , De Wachter Matthias , Dehghani Mohammadreza , D'haenens Erika , Doco‐Fenzy Martine , Geßner Michaela , Gobert Cyrielle , Guliyeva Ulviyya , Haack Tobias B. , Hammer Trine B. , Heinrich Tilman , Hempel Maja , Herget Theresia , Hoffmann Ute , Horvath Judit , Houlden Henry , Keren Boris , Kresge Christina , Kumps Candy , Lederer Damien , Lermine Alban , Magrinelli Francesca , Maroofian Reza , Vahidi Mehrjardi Mohammad Yahya , Moudi Mahdiyeh , Müller Amelie J. , Oostra Anna J. , Pletcher Beth A. , Ros‐Pardo David , Samarasekera Shanika , Tartaglia Marco , Van Schil Kristof , Vogt Julie , Wassmer Evangeline , Winkelmann Juliane , Zaki Maha S. , Zech Michael , Lerche Holger , Radio Francesca Clementina , Gomez‐Puertas Paulino , Møller Rikke S. , Tümer Zeynep
Published: May 2022

Biallelic variants of the gene encoding for the zinc‐finger protein 142 (ZNF142) have recently been associated with intellectual disability (ID), speech impairment, seizures, and movement disorders in nine individuals from five families. In this study, we obtained phenotype and genotype information of 26 further individuals from 16 families. Among the 27 different ZNF142 variants identified in the total of 35 individuals only four were missense. Missense variants may give a milder phenotype by changing the local structure of ZF motifs as suggested by protein modeling; but this correlation should be validated in larger cohorts and pathogenicity of the missense variants should be investigated with functional studies. Clinical features of the 35 individuals suggest that biallelic ZNF142 variants lead to a syndromic neurodevelopmental disorder with mild to moderate ID, varying degrees of delay in language and gross motor development, early onset seizures, hypotonia, behavioral features, movement disorders, and facial dysmorphism. The differences in symptom frequencies observed in the unpublished individuals compared to those of published, and recognition of previously underemphasized facial features are likely to be due to the small sizes of the previous cohorts, which underlines the importance of larger cohorts for the phenotype descriptions of rare genetic disorders.
Ultrasonography in dermatologic surgery: revealing the unseen for improved surgical planning
Authors: Crisan Diana , Wortsman Ximena , Alfageme Fernando , Catalano Orlando , Badea Alexandru , Scharffetter‐Kochanek Karin , Sindrilaru Anca , Crisan Maria
Published: May 2022

Ultrasonography (US) is a modern, in vivo imaging method, which is increasingly being used in dermatology as a complementary tool to clinical examination and dermoscopy. At higher frequencies (15 MHz and above), US is an established method for assessing benign and malignant skin lesions, locoregional staging, monitoring the therapeutic efficacy in various inflammatory skin conditions, and patient follow‐up. One field, which may increasingly benefit from performant imaging techniques such as US is dermatologic surgery. Preoperative imaging of cutaneous tumors, inflammatory skin conditions (hidradenitis suppurativa, abscesses, etc.), or nail pathology provide dermatologic surgeons with relevant information for an optimal surgical planning, identifying potential complex aspects which might require interdisciplinary approaches, herein sparing unnecessary surgical interventions and increasing patients' compliance. In this review, we discuss the increasing significance of US in the field of dermatologic surgery, as well as the spectrum of cutaneous pathology where sonography can aid in the preoperative setting to provide a more precise, individualized surgical planning for better counseling to our patients and improved surgical results.
MicroRNA‐7a‐5p ameliorates diabetic peripheral neuropathy by regulating VDAC1/JNK/c‐JUN pathway
Authors: Jiao Yang , Zhang Yue‐Hua , Wang Chun‐Yan , Yu Yang , Li Yi‐Ze , Cui Wei , Li Qing , Yu Yong‐Hao
Published: May 2022

Aims

The pathogenesis of diabetic peripheral neuropathy (DPN) is complex, and its treatment is extremely challenging. MicroRNA‐7a‐5p (miR‐7a‐5p) has been widely reported to alleviate apoptosis and oxidative stress in various diseases. This study aimed to investigate the mechanism of miR‐7a‐5p in DPN.

Methods

DPN cell model was constructed with high‐glucose–induced RSC96 cells. Cell apoptosis and viability were detected by flow cytometry analysis and cell counting kit‐8 (CCK‐8) assay respectively. The apoptosis and Jun N‐terminal kinase (JNK)/c‐JUN signalling pathway‐related proteins expression were detected by Western blotting. The intracellular calcium content and oxidative stress levels were detected by flow cytometry and reagent kits. Mitochondrial membrane potential was evaluated by tetrechloro‐tetraethylbenzimidazol carbocyanine iodide (JC‐1) staining. The targeting relationship between miR‐7a‐5p and voltage‐dependent anion‐selective channel protein 1 (VDAC1) was determined by RNA pull‐down assay and dual‐luciferase reporter gene assay. The streptozotocin (STZ) rat model was constructed to simulate DPN in vivo. The paw withdrawal mechanical threshold (PTW) was measured by Frey capillary line, and the motor nerve conduction velocity (MNCV) was measured by electromyography.

Results

MiR‐7a‐5p expression was decreased, while VDAC1 expression was increased in HG‐induced RSC96 cells and STZ rats. In HG‐induced RSC96 cells, miR‐7a‐5p overexpression promoted cell proliferation, inhibited apoptosis, down‐regulated calcium release, improved mitochondrial membrane potential and repressed oxidative stress response. MiR‐7a‐5p negatively regulated VDAC1 expression. VDAC1 knockdown improved cell proliferation activity, suppressed cell apoptosis and mitochondrial dysfunction by inhibiting JNK/c‐JUN pathway activation. MiR‐7a‐5p overexpression raised PTW, restored MNCV and reduced oxidative stress levels and nerve cell apoptosis in STZ rats.

Conclusion

MiR‐7a‐5p overexpression ameliorated mitochondrial dysfunction and inhibited apoptosis in DPN by regulating VDAC1/JNK/c‐JUN pathway.
Venous thromboembolism prophylaxis in hospitalized sickle cell disease and sickle cell trait patients
Authors: Ionescu Filip , Anusim Nwabundo , Zimmer Markie , Jaiyesimi Ishmael
Published: May 2022

Introduction

Sickle trait (Hb SA) or sickle disease (Hb SS) carries increased risk of venous thromboembolism (VTE). Hb SS patients are young and lack common comorbid conditions that qualify them for VTE prophylaxis (VTEP).

Methods

Retrospective, multicenter analysis of Hb SS/Hb SA adult patients between January 2013 and December 2018.

Results

There were 803 Hb SA (525 patients) and 1020 Hb SS admissions (262 patients). VTEP use was similar between Hb SA and controls (42% vs. 46%; p‐value = .06) and Hb SS and controls (45% vs. 42%; p‐value = .13). Hb SS/Hb SA patients more frequently received more than half of prescribed doses of VTEP. In multivariate analysis, increasing age and longer hospitalizations were positive predictors. Odds of VTEP use varied with treatment site for Hb SS patients, whereas comorbid conditions, admission hemoglobin and platelet count were not predictive. By contrast, in Hb SA patients, comorbid conditions, higher admission hemoglobin, and higher admission platelet counts raised the odds of VTEP being offered.

Conclusions

VTEP is underused in Hb SS/Hb SA patients. There may be a trend toward offering more VTEP in Hb SS disease, but not in Hb SA patients, where VTEP prescribing is driven by comorbid conditions rather than genotype. Patient compliance does not appear to play a major role, but intercenter variability suggests provider education may improve VTEP use.
Impoundment increases methane emissions in Phragmites‐invaded coastal wetlands
Authors: Sanders‐DeMott Rebecca , Eagle Meagan J. , Kroeger Kevin D. , Wang Faming , Brooks Thomas W. , O'Keefe Suttles Jennifer A. , Nick Sydney K. , Mann Adrian G. , Tang Jianwu
Published: May 2022

Saline tidal wetlands are important sites of carbon sequestration and produce negligible methane (CH4) emissions due to regular inundation with sulfate‐rich seawater. Yet, widespread management of coastal hydrology has restricted tidal exchange in vast areas of coastal wetlands. These ecosystems often undergo impoundment and freshening, which in turn cause vegetation shifts like invasion by Phragmites, that affect ecosystem carbon balance. Understanding controls and scaling of carbon exchange in these understudied ecosystems is critical for informing climate consequences of blue carbon restoration and/or management interventions. Here, we (1) examine how carbon fluxes vary across a salinity gradient (4–25 psu) in impounded and natural, tidally unrestricted Phragmites wetlands using static chambers and (2) probe drivers of carbon fluxes within an impounded coastal wetland using eddy covariance at the Herring River in Wellfleet, MA, United States. Freshening across the salinity gradient led to a 50‐fold increase in CH4 emissions, but effects on carbon dioxide (CO2) were less pronounced with uptake generally enhanced in the fresher, impounded sites. The impounded wetland experienced little variation in water‐table depth or salinity during the growing season and was a strong CO2 sink of −352 g CO2‐C m−2 year−1 offset by CH4 emission of 11.4 g CH4‐C m−2 year−1. Growing season CH4 flux was driven primarily by temperature. Methane flux exhibited a diurnal cycle with a night‐time minimum that was not reflected in opaque chamber measurements. Therefore, we suggest accounting for the diurnal cycle of CH4 in Phragmites, for example by applying a scaling factor developed here of ~0.6 to mid‐day chamber measurements. Taken together, these results suggest that although freshened, impounded wetlands can be strong carbon sinks, enhanced CH4 emission with freshening reduces net radiative balance. Restoration of tidal flow to impounded ecosystems could limit CH4 production and enhance their climate regulating benefits.
Depression and quality of life in older adults with atrial fibrillation: A cross‐sectional community‐based study
Authors: Senoo Keitaro , Yukawa Arito , Ohkura Takashi , Iwakoshi Hibiki , Nishimura Tetsuro , Teramukai Satoshi , Narumoto Jin , Matoba Satoaki
Published: May 2022

Aim

In the older population, depression often occurs alongside physical illness. A cross‐sectional community‐based study examined the relationship between atrial fibrillation (AF), depression, and quality of life (QoL), and the impact of chest symptoms.

Methods

A total of 1364 older adults (≥65 years) who attended AF awareness symposia from July 2019 to December 2020 provided consent to participate in the study and valid questionnaire responses. Depression was assessed with the Geriatric Depression Scale (GDS)‐15, and QoL with the 12‐item Short‐Form Health Survey (SF‐12).

Results

AF patients (n = 130) were divided into symptomatic AF (n = 87) and asymptomatic AF (n = 43) groups. Depressive state and physical component summary (PCS) and mental component summary (MCS) in the SF‐12 were compared with the control group (non‐AF group without chest symptoms, n = 911), extracted from the same symposium participants. The depression rate (defined as GDS‐15 ≥ 10) was 9.2% in symptomatic AF patients, 2.3% in asymptomatic AF patients, and 2.7% in controls. The mean PCS and MCS in each group were 43.4 ± 10.8 and 54.8 ± 8.6, 44.6 ± 10.7 and 57.3 ± 7.3, and 48.5 ± 7.9 and 56.7 ± 6.8, respectively. Multivariate regression analysis showed that symptomatic AF patients had a higher risk of depression (odds ratio: 3.46, 95% confidence interval (CI) 1.27–8.57, P = 0.01) and poor QoL (PCS: B −3.17, 95% CI −5.05 to −1.29, P = 0.001 and MCS: B −1.80, 95% CI −3.45 to −0.16, P = 0.03) compared with controls, but asymptomatic AF patients did not.

Conclusions

In a cross‐sectional community‐based study, symptomatic AF patients were vulnerable to depression and poor QoL, but asymptomatic AF patients were not. Geriatr Gerontol Int 2022; 22: 505–510.
The healthcare experiences of women with cardiac disease in pregnancy and postpartum: A qualitative study
Authors: Hutchens Jane , Frawley Jane , Sullivan Elizabeth A.
Published: May 2022

Introduction

Cardiac disease affects an estimated 1%–4% of all pregnancies and is a leading cause of maternal morbidity and mortality. There is a lack of data on the healthcare experiences of affected women to inform health service delivery and person‐centred care. This study sought to explore and understand the healthcare experiences of women with cardiac disease in pregnancy and postpartum.

Methods

This qualitative study used semi‐structured interviews with women who had cardiac disease in pregnancy or the first 12 months postpartum. Data were analysed using thematic analysis.

Results

Participants were 25 women with pre‐existing or newly diagnosed acquired, genetic and congenital cardiac disease. Analysis of the interviews highlighted the discrepancy between care aspirations and experiences. The participants had a wide range of cardiac diseases and timing of diagnoses, but had similar healthcare experiences of being dismissed, not receiving the information they required, lack of continuity of care and clinical guidelines and of feeling out of place within a healthcare system that did not accommodate their combined needs as a mother and a cardiac patient.

Conclusion

This study identified a lack of person‐centred care and responsiveness of the healthcare system in providing fit‐for‐purpose healthcare for women with complex disease who are pregnant or new mothers. In particular, cardiac and maternity care providers have an opportunity to listen to women who are the experts on their emergent healthcare needs, contributing to development of the knowledge base on the healthcare experiences of having cardiac disease in pregnancy and postpartum.

Patient or Public Contribution

Public and patient input into the value and design of the study was gained through NSW Heart Foundation forums, including the Heart Foundation's women's patient group.