bluuebunny/crossref_metadata_2025_split huggingface dataset:
Avoidable Adverse Events Related to Ignoring the Do-Not-Do Recommendations: A Retrospective Cohort Study Conducted in the Spanish Primary Care Setting
Authors: Mira José Joaquín , Carrillo Irene , Pérez-Pérez Pastora , Astier-Peña Maria Pilar , Caro-Mendivelso Johanna , Olivera Guadalupe , Silvestre Carmen , Nuín Mª Angeles , Aranaz-Andrés Jesús M. ,   on behalf the SOBRINA Research Team
Published: April 2021

Objective
This study aimed to measure the frequency and severity of avoidable adverse events (AAEs) related to ignoring do-not-do recommendations (DNDs) in primary care.

Methods
A retrospective cohort study analyzing the frequency and severity of AAEs related to ignoring DNDs (7 from family medicine and 3 from pediatrics) was conducted in Spain. Data were randomly extracted from computerized electronic medical records by a total of 20 general practitioners and 5 pediatricians acting as reviewers; data between February 2018 and September 2019 were analyzed.

Results
A total of 2557 records of adult and pediatric patients were reviewed. There were 1859 (72.7%) of 2557 (95% confidence interval [CI], 71.0%–74.4%) DNDs actions in 1307 patients (1507 were performed by general practitioners and 352 by pediatricians). Do-not-do recommendations were ignored more often in female patients (P < 0.0001). Sixty-nine AAEs were linked to ignoring DNDs (69/1307 [5.3%]; 95% CI, 4.1%–6.5%). Of those, 54 (5.1%) of 1062 were in adult patients (95% CI, 3.8%–6.4%) and 15 (6.1%) of 245 in pediatric patients (95% CI, 3.1%–9.1%). In adult patients, the majority of AAEs (51/901 [5.7%]; 95% CI, 4.2%–7.2%) occurred in patients 65 years or older. Most AAEs were characterized by temporary minor harm both in adult patients (28/54 [51.9%]; 95% CI, 38.5%–65.2%) and pediatric patients (15/15 [100%]).

Conclusions
These findings provide a new perspective about the consequences of low-value practices for the patients and the health care systems. Ignoring DNDs could place patients at risk, and their safety might be unnecessarily compromised.

Trial Registration Number
NCT03482232.
Closure of Challenging Pediatric Scalp Wounds by a Tension-Relief System
Authors: Olshinka Asaf , Ad-El Dean , Kalish Eyal , Shay Tamir , Yaacobi Dafna Shilo 
Published: April 2021

AbstractPediatric scalp defects may be challenging, due to their variant tension level and specific etiologies. Tissue characteristics and pre- and post-management considerations may pose difficulties to reconstruction in the pediatric patient. Primary closure is the preferred surgical technique but is not always possible. Various techniques have been described for facilitating primary wound closure, by reducing tension from the skin wound margins. The authors use a tension-relief system in some challenging scalp wounds when simple primary closure cannot be achieved. This enables primary closure without tension on the surgical margins, and may thus preclude the need for other closure techniques such as tissue-expanders, grafts, and flaps. The authors describe our use of a tension-relief system in 21 pediatric patients treated during 2017–2020, for congenital deformities, vascular malformations and other skin lesions, traumatic wounds, burn scars, and complicated surgical wounds with and without hardware exposure. A tension-relief system is a prompt, simple-to-use, safe, and low-cost surgical solution that offers several advantages over other techniques when tension-free primary intention closure is not possible. These benefits include less extensive surgery, fewer surgeries and associated anesthesia, shorter treatment period and hospitalization, better scarring, lower distress and burden to patients and their families, better pain-control, the absence of donor-site with its comorbidities, and less bleeding and risk of damaging adjacent structures. Based on our experience and the system characteristics detailed, the authors recommend using the described technique, which is convenient, accessible, and reliable, to close challenging scalp wounds in pediatric patients.
Changes in the Transcriptome and Proteome of Cartilage in Microtia
Authors: Dong Weiwei , Jiang Haiyue , He Leren , Pan Bo , Yang Qinghua 
Published: April 2021

Abstract
Congenital microtia is a severe physiological defect and is among the most common craniofacial defects. It is characterized by severe auricle dysplasia, external auditory canal atresia or stenosis, and middle ear malformation, though inner ear development is mostly normal with some hearing occurring through bone conduction. Auricular reconstruction is the only treatment for congenital microtia. In this study, the authors integrated messenger ribonucleic acid and mass spectrometry data of cartilage obtained from the affected and unaffected sides of 16 unilateral microtia patients who had undergone ear reconstruction surgery. The authors next performed functional analyses to investigate differences in the proteome of the affected and unaffected ears to elicit molecular pathways involved in microtia pathogenesis. The authors collected 16 pairs samples. Proteomic and transcriptomic analyses identified 47 genes that were differentially expressed in affected and unaffected cartilage. Integrated pathway analysis implicated the involvement of genes related to cell adhesion, extracellular matrix organization, and cell migration in disease progression. Through the integration of gene and protein expression data in human primary chondrocytes, the authors identified molecular markers of microtia progression that were replicated across independent datasets and that have translational potential.
Association Between Anterior Cingulate Cortex Neurochemical Profile and Clinical Remission After Electroconvulsive Treatment in Major Depressive Disorder
Authors: Ermis Cagatay , Aydin Burc , Kucukguclu Semih , Yurt Aysegul , Renshaw Perry F. , Yildiz Aysegul 
Published: April 2021

Background
The aim of the study was to assess anterior cingulate cortex (ACC) neurochemical profile of patients with unipolar major depressive disorder (MDD) before and after electroconvulsive therapy (ECT) by using 1H magnetic resonance spectroscopy (1H-MRS).

Method
Using 1H-MRS, the metabolite levels of choline, glutamate + glutamine (Glx), myo-inositol, N-acetylaspartate, and total creatine were measured in ACC before and after 4-week ECT. The Montgomery-Åsberg Depression Rating Scale (MADRS) was implemented by blind raters to evaluate the efficacy of the treatment. Electroconvulsive therapy–remitter (ER) and nonremitter groups were compared using the 1-way repeated measures analysis of variance.

Results
Thirty patients with unipolar MDD (aged 41.3 ± 10.0 years, 66.7% female) were included in the study. The ER group (n = 16, 53.3%) and NR group did not differ regarding baseline Global Assessment of Functioning and MADRS scores. At the end of 4-week ECT treatment, results did not suggest any significant difference for metabolite levels in ACC. When compared with the NR group, the ER group had higher baseline levels of Glx (8.8 ± 1.8 vs 6.3 ± 2.0, P = 0.005) and total creatine (5.3 ± 0.6 vs 4.7 ± 0.5, P = 0.010). In addition, elevated baseline Glx (r = −0.68, P = 0.002) was associated with lower MADRS scores at the end treatment. Finally, the change in Glx levels was correlated with change in MADRS scores after ECT (r = 0.47, P = 0.049).

Limitations
Modest sample size and 1H-MRS at 1.5 Tesla are limitations of the study.

Conclusions
Results suggested that Glx levels could be a predictor of remission. Studies with larger samples should explore neurochemical correlates of ECT in unipolar MDD.
HIV-1 evolutionary dynamics under non-suppressive antiretroviral therapy
Authors: Kemp Steven A. , Charles Oscar J. , Derache Anne , Smidt Werner , Martin Darren P. , Pillay Deenan , Goldstein Richard A. , Gupta Ravindra K. 
Published: April 2021

AbstractProlonged virologic failure on 2nd-line protease inhibitor (PI) based ART without emergence of major protease mutations is well recognised and provides an opportunity to study within-host evolution in long-term viraemic individuals. Using next-generation sequencing and in silico haplotype reconstruction we analysed whole genome sequences from longitudinal plasma samples of eight chronically infected HIV-1 individuals failing 2nd-line regimens from the ANRS 12249 TasP trial. On non-suppressive ART, there were large fluctuations in synonymous and non-synonymous variant frequencies despite stable viraemia. Reconstructed haplotypes provided evidence for selective sweeps during periods of partial adherence, and viral haplotype competition during periods of low drug exposure. Drug resistance mutations in reverse transcriptase (RT) were used as markers of viral haplotypes in the reservoir and their distribution over time indicated recombination. We independently observed linkage disequilibrium decay, indicative of recombination. These data highlight dramatic changes in virus population structure that occur during stable viremia under non suppressive ART.
CoVac501, a self-adjuvanting peptide vaccine conjugated with TLR7 agonists, against SARS-CoV-2 induces protective immunity
Authors: Long Yiru , Sun Jianhua , Liu Tingting , Tang Feng , Zhang Xinxin , Qin Qiuping , Miao Yunqiu , Zhu Weiliang , Pan Xiaoyan , An Qi , Qin Mian , Tong Xiankun , Peng Xionghua , Yu Pan , Zhu Peng , Zhang Yachun , Zhang Leike , Xiao Gengfu , Zuo Jianping , Tang Wei , Zhou Ji , Xu Zhijian , Gan Yong , Ren Jin , Huang Wei , Jin Guangyi , Gong Likun 
Published: April 2021

AbstractSafe, economical and effective vaccines against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are needed to achieve adequate herd immunity and halt the pandemic. We have constructed a novel SARS-CoV-2 vaccine, CoVac501, which is a self-adjuvanting peptide vaccine conjugated with Toll-like receptor 7 (TLR7) agonists. The vaccine contains two immunodominant peptides screened from receptor-binding domain (RBD) and is fully chemically synthesized. And the vaccine has optimized nanoemulsion formulation, outstanding stability and safety. In non-human primates (NHPs), CoVac501 elicited high and persistent titers of RBD-specific and protective neutralizing antibodies (NAbs), which were also effective to RBD mutations. CoVac501 was found to elicit the increase of memory T cells, antigen-specific CD8+T cell responses and Th1-biased CD4+T cell immune responses in NHPs. More importantly, the sera from the immunized NHPs can prevent infection of live SARS-CoV-2 in vitro.One-Sentence SummaryA novel SARS-CoV-2 vaccine we developed, CoVac501, which is a fully chemically synthesized and self-adjuvanting peptides conjugated with TLR7 agonists, can induce high-efficient humoral and cellular immune responses against SARS-CoV-2.
Interannual temporal patterns of DeSoto Canyon macrofauna and evaluation of influence from the Deepwater Horizon
Authors: Shantharam Arvind K. , Baco Amy R. 
Published: April 2021

AbstractSubmarine canyons are highly dynamic and productive ecosystems, but time-series studies of metazoan benthic communities in canyons are scarce. Deep-sea macrofauna from the DeSoto Canyon in the northern Gulf of Mexico were sampled annually from 2012 through 2014 from five stations within the Canyon and from two stations in 2013 and 2014 on the adjacent open slope, for analysis of interannual dynamics, temporal variability, and potential influence of the Deepwater Horizon oil spill (DwH), which occurred nearby in 2010. At a few sites, elevated abundance was observed at the start of the time-series for overall macrofauna and for deposit feeder abundance. However, diversity metrics showed no difference within stations among time points. Community and feeding guild structure varied by station, as expected, but showed no statistical difference among time points within a station. Some temporal variability was visible in temporal trajectory overlays. Cluster analyses showed grouping more by station than by time point. Metrics utilized for measuring potential oil contamination impact and overall community stress including the benthic polychaete/amphipod ratio, feeding guild abundance, macrofaunal indicators designed from the DwH, and community dispersion, generally exhibited a paucity of evidence of impact, both yearly and with site-to-site comparisons. This suggests low levels of impact in the canyon consistent with the low deposition of hydrocarbons, the timing of sampling, and quick recovery of canyon foraminifera. Taken together these results suggest relatively low levels of temporal variability within the DeSoto Canyon macrofauna with little evidence of oil influence on these sites within the studied time range.
Single-cell profiling of environmental enteropathy reveals signatures of epithelial remodeling and immune activation in severe disease
Authors: Kummerlowe Conner , Wallach Thomas , Mwakamui Simutanyi , Hughes Travis K. , Mulugeta Nolawit , Mudenda Victor , Besa Ellen , Zyambo Kanekwa , Fleming Ira , Vukovic Marko , Doran Ben A. , Aicher Toby P. , Wadsworth Marc H. , Bramante Juliet Tongue , Uchida Amiko M. , Fardoos Rabiah , Asowata Osaretin E. , Herbert Nicholas , Kløverpris Henrik N. , Garber John J. , Ordovas-Montanes Jose , Gartner Zev , Shalek Alex K. , Kelly Paul 
Published: April 2021

AbstractEnvironmental enteropathy (EE) is a subclinical condition of the small intestine that is highly prevalent in low- and middle-income countries. It is thought to be a key contributing factor to childhood malnutrition, growth-stunting, and diminished oral vaccine responses. While EE has been shown to be the by-product of recurrent enteric infection, its full pathophysiology remains unclear. Here, we mapped the cellular and molecular correlates of EE severity by performing high-throughput single-cell RNA-sequencing on 33 small intestinal biopsies from 11 adults with EE from Lusaka, Zambia (8 HIV-negative, 3 HIV-positive), 6 adults without EE in Boston, USA, and 2 adults from Durban, South Africa, which we complemented with published data from 3 additional South African adults from the same clinical site. By using these data to reanalyze previously-defined bulk-transcriptomic signatures of reduced villus height and decreased plasma LPS levels in EE, we found that these signatures may be driven by an increased abundance of surface mucosal cells – a gastric-like subset previously implicated in epithelial repair in the gastrointestinal tract. In addition, we identified several cell subsets whose fractional abundances associate with histologically determined EE severity, small intestinal region, and HIV infection. Furthermore, by comparing distal duodenal EE samples with those from three control cohorts, we identified dysregulated WNT and MAPK signaling in the EE epithelium and a T cell subset highly expressing a transcriptional signature of tissue-resident memory cells but with increased pro-inflammatory cytokine expression in the EE cohort. Altogether, our work illuminates epithelial and immune correlates of EE and provides new molecular targets for intervention.One Sentence SummaryUsing single-cell RNA-sequencing, we characterize the pathophysiology of environmental enteropathy (EE) – a highly prevalent condition of the small intestine that is thought to be a primary cause of global growth-stunting cases and a key contributing factor to childhood malnutrition and diminished oral vaccine responses – to derive insights into the epithelial and immune correlates of disease severity, suggesting new therapeutic targets for future investigation.
Adhesion dynamics regulate cell intercalation behaviour in an active tissue
Authors: Nestor-Bergmann Alexander , Blanchard Guy B. , Hervieux Nathan , Fletcher Alexander G. , Étienne Jocelyn , Sanson Bénédicte 
Published: April 2021

ABSTRACTCell intercalation is a key cell behaviour of morphogenesis and wound healing, where local cell neighbour exchanges can cause dramatic tissue deformations such as body axis extension. Here, we develop a mechanical model to understand active cell intercalation behaviours in the context of an epithelial tissue. Extending existing descriptions, such as vertex models, the junctional actomyosin cortex of every cell is modelled as a continuum morphoelastic rod, explicitly representing cortices facing each other at bicellular junctions. Cells are described directly in terms of the key subcellular constituents that drive dynamics, with localised stresses from the contractile actomyosin cortex and adhesion molecules coupling apposed cortices. This multi-scale apposed-cortex formulation reveals key behaviours that drive tissue dynamics, such as cell-cell shearing and flow of junctional material past cell vertices. We show that cell neighbour exchanges can be driven by purely junctional mechanisms. Active contractility and viscous turnover in a single bicellular junction are sufficient to shrink and remove a junction. Next, the 4-way vertex is resolved and a new, orthogonal junction extends passively. The adhesion timescale defines a frictional viscosity that is an important regulator of these dynamics, modulating tension transmission in the tissue as well as the speeds of junction shrinkage and growth. The model additionally predicts that rosettes, which form when a vertex becomes common to many cells, are likely to occur in active tissues with high adhesive friction.SIGNIFICANCECell intercalation, or neighbour exchange, is a crucial behaviour that can drive tissue deformations, dissipate stress and facilitate wound healing. Substantial experimental work has identified the key molecular players facilitating intercalation, but there remains a lack of consensus and understanding of their physical roles. Existing biophysical models that represent cell-cell contacts with single edges cannot study the continuous dynamics of intercalation, involving shear between coupled cell cortices. Deriving a continuum description of the cell cortex, explicitly coupling neighbouring cortices with adhesions, we define the biophysical conditions required for successful neighbour exchanges. Furthermore, we show how the turnover of adhesion molecules specifies a viscous friction that regulates active tissue dynamics.
Prediction and evolution of the molecular fitness of SARS-CoV-2 variants: Introducing SpikePro
Authors: Pucci Fabrizio , Rooman Marianne 
Published: April 2021

AbstractThe understanding of the molecular mechanisms driving the fitness of the SARS-CoV-2 virus and its mutational evolution is still a critical issue. We built a simplified computational model, called SpikePro, to predict the SARS-CoV-2 fitness from the amino acid sequence and structure of the spike protein. It contains three contributions: the viral transmissibility predicted from the stability of the spike protein, the infectivity computed in terms of the affinity of the spike protein for the ACE2 receptor, and the ability of the virus to escape from the human immune response based on the binding affinity of the spike protein for a set of neutralizing antibodies. Our model reproduces well the available experimental, epidemiological and clinical data on the impact of variants on the biophysical characteristics of the virus. For example, it is able to identify circulating viral strains that, by increasing their fitness, recently became dominant at the population level. SpikePro is a useful instrument for the genomic surveillance of the SARS-CoV-2 virus, since it predicts in a fast and accurate way the emergence of new viral strains and their dangerousness. It is freely available in the GitHub repository github.com/3BioCompBio/SpikeProSARS-CoV-2.
Caenorhabditis elegansLET-413 Scribble is essential in the epidermis for growth, viability, and directional outgrowth of epithelial seam cells
Authors: Riga Amalia , Cravo Janine , Schmidt Ruben , Pires Helena R. , Castiglioni Victoria G. , van den Heuvel Sander , Boxem Mike 
Published: April 2021

AbstractThe conserved adapter protein Scribble (Scrib) plays essential roles in a variety of cellular processes, including polarity establishment, proliferation, and directed cell migration. While the mechanisms through which Scrib promotes epithelial polarity are beginning to be unraveled, its roles in other cellular processes including cell migration remain enigmatic. InC. elegans, the Scrib ortholog LET-413 is essential for apical–basal polarization and junction formation in embryonic epithelia. However, whether LET-413 is required for postembryonic development or plays a role in migratory events is not known. Here, we use inducible protein degradation to investigate the functioning of LET-413 in larval epithelia. We find that LET-413 is essential in the epidermal epithelium for growth, viability, and junction maintenance. In addition, we identify a novel role for LET-413 in the polarized outgrowth of the epidermal seam cells. These stem cell-like epithelial cells extend anterior and posterior directed apical protrusions in each larval stage to reconnect to their neighbors. We show that the role of LET-413 in seam cell outgrowth is mediated at least in part by the junctional component DLG-1 discs large, which appears to restrict protrusive activity to the apical domain. Finally, we demonstrate that the Rho-family GTPases CED-10 Rac and CDC-42 can regulate seam cell outgrowth and may also function downstream of LET-413. Our data uncover multiple essential functions for LET-413 in larval development and shed new light on the regulation of polarized outgrowth of the seam cells.
Early Patellofemoral Cartilage and Bone Degeneration in a Rat Model of Noninvasive Anterior Cruciate Ligament Rupture
Authors: Hartner Samantha E. , Newton Michael D. , Fleischer Mackenzie M. , Baker Kevin C. , Maerz Tristan 
Published: April 2021

ABSTRACTBackgroundAnterior cruciate ligament rupture (ACLR) is a well-known risk factor for the development of post-traumatic osteoarthritis (PTOA). While clinical and pre-clinical studies have characterized the onset and progression of PTOA in the tibiofemoral joint compartment, very little is known about degenerative changes in the patellofemoral compartment after ACL injury.Hypothesis/PurposeTo evaluate the extent to which ACL rupture induces acute patellofemoral joint degeneration by quantifying articular cartilage morphology and remodeling of subchondral and trabecular bone microarchitecture in the patellofemoral compartment.Study DesignDescriptive laboratory study.MethodsAdult female Lewis rats were randomized to undergo either a non-surgical ACL rupture or a Sham procedure (n = 6 per group).Ex vivocontrast-enhanced micro-computed tomography (µCT) and histological evaluation of the patellofemoral compartment were performed at 2-weeks post-injury, representing a timepoint of documented early PTOA in the tibiofemoral compartment in this model.ResultsACL rupture causes osteophyte formation in the patella and mild degeneration in the superficial zone of articular cartilage (AC), including surface fibrillation, fissures, increased cellularity, and abnormal chondrocyte clustering at two weeks post-injury. Contrast-enhanced µCT analysis demonstrates significant increases in AC thickness of patellar and trochlear cartilage. Loss of subchondral bone thickness, bone volume fraction, and tissue mineral density, as well as changes to trabecular microarchitecture in both the patella and trochlea, were indicative of catabolic bone remodeling.ConclusionThese results demonstrate that the patellofemoral joint develops mild but evident degenerative changes in the acute time period following ACL rupture, extending the utility of this rat model to the study of degenerative patellofemoral changes following joint trauma.Clinical RelevanceACL rupture causes mild degeneration and swelling of articular cartilage, coupled with catabolic bone remodeling in the patellofemoral compartment. Characterizing the pathophysiology of patellofemoral PTOA in its early stages may provide a better understanding of disease progression and provide opportunities for preventative therapeutic intervention.