bluuebunny/crossref_metadata_2025 huggingface dataset:
Transient and DNA-free in vivo CRISPR/Cas9 genome edition for flexible modelling of endometrial carcinogenesis
Authors: Navaridas Raúl , Vidal-Sabanés Maria , Ruiz-Mitjana Anna , Perramon-Güell Aida , Megino-Luque Cristina , Llobet-Navas David , Matias-Guiu Xavier , Egea Joaquim , Encinas Mario , Bardia Lídia , Colombelli Julien , Dolcet Xavier
Published: June 2022

The CRISPR/Cas9 technology has emerged as a powerful tool to generate mouse models of disease. Endometrial cancer is the most common malignancy of the female genital tract. In the present study, we have developed a pipeline for the generation of somatically engineered mouse models of endometrial cancer by in vivo electroporation-mediated delivery of Cas9 ribonucleoprotein into the uterine cavity. By using mT/mG dual-fluorescent reporter mice, we show that this system allows an efficient genomic edition specifically in epithelial endometrial cells. As a proof of its applicability for endometrial cancer modeling, we designed Cas9 ribonucleoprotein targeting Pten, the most frequently tumor suppressor gene mutated in this type of cancer. Pten-targeting ribonucleoprotein delivery into the uterine cavity caused loss of expression of PTEN protein in epithelial endometrial cells that resulted in the development of endometrial lesions. We also validated this technique for gene edition in other important endometrial driver genes such as p53 or Fbxw7. By co-targeting LoxP sites of mT/mG reporter mice and Pten, we demonstrate the generation of differentially edited cell populations that may be a useful tool to model tumoral heterogeneity. Moreover, the combination of CRISPR/Cas9 technology in mT/mG dual-reporter mice and light-sheet microscopy represents an interesting approach for in vivo cancer cell tracing. This methodology opens a new door for future rapid, flexible, customizable and multiplexable in vivo modeling of endometrial cancer.
Use of a MAIT activating ligand, 5-OP-RU, as a mucosal adjuvant in a murine model of Vibrio cholerae O1 vaccination
Authors: Jensen Owen , Trivedi Shubhanshi , Li Kelin , Aubé Jeffrey , Hale J. Scott , Ryan Edward T. , Leung Daniel T.
Published: June 2022

Background

Mucosal-associated invariant T (MAIT) cells are innate-like T cells enriched in the mucosa with capacity for B cell help. We hypothesize that targeting MAIT cells, using a MAIT activating ligand as an adjuvant, could improve mucosal vaccine responses to bacterial pathogens.

Methods

We utilized murine models of Vibrio cholerae vaccination to test the adjuvant potential of the MAIT activating ligand, 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU). We measured V. cholerae-specific antibody and antibody-secreting cell responses, and used flow cytometry to examine MAIT cell and B cell phenotype, in blood, bronchoalveolar lavage fluid (BALF), and mucosal tissues, following intranasal vaccination with live V. cholerae O1 or a V. cholerae O1 polysaccharide conjugate vaccine.

Results

We report significant expansion of MAIT cells in the lungs of 5-OP-RU treated mice, and increases in BALF V. cholerae O-specific-polysaccharide IgG responses in our conjugate vaccine model adjuvanted with low-dose 5-OP-RU. No significant differences in humoral responses were found in our live V. cholerae vaccination model.

Conclusions

Using a murine model, we demonstrate the potential, as well as the limitations, of targeting MAIT cells to improve antibody responses to a mucosal cholera vaccine. Our study highlights the need for future research optimizing MAIT cell targeting for improving mucosal vaccines.

One Sentence Summary

Targeting mucosal-associated invariant T (MAIT) cells with a mucosal adjuvant in an intranasal cholera vaccine model resulted in significant expansion of lung MAIT cells, but limited improvements in cholera-specific antibody responses.
Exploration, representation and rationalization of the conformational phase-space of N-glycans
Authors: Grothaus Isabell Louise , Bussi Giovanni , Ciacchi Lucio Colombi
Published: June 2022

Despite their fundamental biological relevance, structure-property relationships inN-glycans are fundamentally lacking, and their highly multidimensional compositional and conformational phase-spaces remain largely unexplored. The torsional flexibility of the glycosidic linkages and the ring dynamics result in wide, rugged free-energy landscapes that are difficult to sample in molecular dynamics simulations. We show that a novel enhanced-sampling scheme combining replica-exchange with solute and collective-variable tempering, enabling transitions over all relevant energy barriers, delivers converged distributions of solvatedN-glycan conformers. Several dimensionality-reduction algorithms are compared and employed to generate conformational free-energy maps in two-dimensions. Together with an originally developed conformation-based nomenclature scheme that uniquely identify glycan conformers, our modelling procedure is applied to reveal the effect of chemical substitutions on the conformational ensemble of selected high-mannose-type and complex glycans. Moreover, the structure-prediction capabilities of two commonly used glycan force fields are assessed via the theoretical prediction of experimentally available NMR J-coupling constants. The results confirm the key role of especiallyωand ψ torsion angles in discriminating between different conformational states, and suggest an intriguing correlation between the torsional and ring-puckering degrees of freedom that may be biologically relevant.

Abstract Figure
eDNA-stimulated cell dispersion fromCaulobacter crescentusbiofilms upon oxygen limitation is dependent on a toxin-antitoxin system
Authors: Berne Cecile , Zappa Sébastien , Brun Yves V.
Published: June 2022

In their natural environment, most bacteria preferentially live as complex surface-attached multicellular colonies called biofilms. Biofilms begin with a few cells adhering to a surface, where they multiply to form a mature colony. When conditions deteriorate, cells can leave the biofilm. This dispersion is thought to be an important process that modifies the overall biofilm architecture and that promotes colonization of new environments. InCaulobacter crescentusbiofilms, extracellular DNA (eDNA) is released upon cell death and prevents newborn cells from joining the established biofilm. Thus, eDNA promotes the dispersal of newborn cells and the subsequent colonization of new environments. These observations suggest that eDNA is a cue for sensing detrimental environmental conditions in the biofilm. Here we show that the toxin-antitoxin ParDE4stimulates cell death in areas of a biofilm with decreased O2availability. In conditions where O2availability is low, eDNA concentration is correlated with cell death. Cell dispersal away from biofilms is decreased whenparDE4is deleted, probably due to the lower local eDNA concentration. Expression ofparDE4is positively regulated by O2and the expression of this operon is decreased in biofilms where O2availability is low. Thus, PCD by an O2-regulated toxin-antitoxin system stimulates dispersal away from areas of a biofilm with decreased O2availability and favors colonization of a new, more hospitable environment.
Distributing task-related neural activity across a cortical network through task-independent connections
Authors: Kim Christopher M. , Finkelstein Arseny , Chow Carson C. , Svoboda Karel , Darshan Ran
Published: June 2022

Task-related neural activity is widespread across populations of neurons during goal-directed behaviors. However, little is known about the synaptic reorganization and circuit mechanisms that lead to broad activity changes. Here we trained a limited subset of neurons in a spiking network with strong synaptic interactions to reproduce the activity of neurons in the motor cortex during a decision-making task. We found that task-related activity, resembling the neural data, emerged across the network, even in the untrained neurons. Analysis of trained networks showed that strong untrained synapses, which were independent of the task and determined the dynamical state of the network, mediated the spread of task-related activity. Optogenetic perturbations suggest that the motor cortex is strongly-coupled, supporting the applicability of the mechanism to cortical networks. Our results reveal a cortical mechanism that facilitates distributed representations of task-variables by spreading the activity from a subset of plastic neurons to the entire network through task-independent strong synapses.
Making a pathogen? Evaluating the impact of protist predation on the evolution of virulence inSerratia marcescens
Authors: Hopkins Heather A. , Lopezguerra Christian , Lau Meng-Jia , Raymann Kasie
Published: June 2022

Opportunistic pathogens are environmental microbes that are generally harmless and only occasionally cause disease. Unlike obligate pathogens, the growth and survival of opportunistic pathogens does not rely on host infection or transmission. Their versatile lifestyles make it challenging to decipher how and why virulence has evolved in opportunistic pathogens. The Coincidental Evolution Hypothesis (CEH) postulates that virulence results from exaptation or pleiotropy, i.e., traits evolved for adaptation to living in one environment that have a different function in another. In particular, adaptation to avoid or survive protist predation has been suggested to contribute to the evolution of bacterial virulence (the training grounds hypothesis). Here we used experimental evolution to determine how the selective pressure imposed by a protist predator impacts the virulence and fitness of a ubiquitous environmental opportunistic bacterial pathogen that has acquired multi-drug resistance:Serratia marcescens. To this aim, we evolvedS. marcescensin the presence or absence of generalist protist predator,Tetrahymena thermophila. After 60 days of evolution, we evaluated genotypic and phenotypic changes by comparing evolvedS. marcescensto the ancestral strain. Whole genome shotgun (WGS) sequencing of the entire evolved populations and individual isolates revealed numerous cases of parallel evolution, many more than statistically expected by chance, in genes associated with virulence. Our phenotypic assays suggested that evolution in the presence of a predator maintained virulence, whereas evolution in the absence of a predator resulted in attenuated virulence. We also found a significant correlation between virulence, biofilm formation, and grazing resistance. Overall, our results provide evidence that bacterial virulence and virulence related traits are maintained by selective pressures imposed by protist predation.
Evaluation of standard treatments for managing adult Japanese patients with inadequately controlled moderate‐to‐severe atopic dermatitis: Two‐year data from the ADDRESS‐J disease registry
Authors: Katoh Norito , Saeki Hidehisa , Kataoka Yoko , Etoh Takafumi , Teramukai Satoshi , Takagi Hiroki , Fujita Hiroyuki , Ardeleanu Marius , Rizova Elena , Arima Kazuhiko ,   the ADDRESS‐J Investigators
Published: June 2022

Atopic dermatitis (AD), a chronic relapsing inflammatory skin disease with a high disease burden, is one of the most common dermatological conditions in Japan. Herein, we report the disease profiles and current AD treatment during 2‐year management of Japanese adults with moderate‐to‐severe AD. ADDRESS‐J was a prospective, longitudinal, observational study that evaluated real‐world effectiveness and safety of current AD treatments of adult patients with moderate‐to‐severe AD (Investigator's Global Assessment score 3 or 4) in Japan. The maximum follow‐up period was 2 years. Among 300 patients enrolled, 288 had ≥1 post‐baseline evaluation and were analyzed (mean age, 35.5 years; 60.1% male). Almost all patients (99.7%) received topical therapy; the most commonly used therapy was topical corticosteroids of the second‐highest potency (86.5%) (e.g., 0.1% mometasone furoate) followed by medium‐potency topical corticosteroids (50.3%) (e.g., 0.05% clobetasol butyrate). At month 12 of the study, 10.4% of patients had Investigator's Global Assessment 0/1, similarly at month 24 (10.8%). A total of 132 patients (45.8%) had ≥1 AD flare‐up during the observation period, with the majority of first flares occurring within the first year of the study. Various physician‐ and patient‐reported outcomes improved considerably during the first 3 months of the study, with only minor changes after this time. In this cohort, 16.7% of patients had skin infections requiring treatment; 7.3% had adverse events (AE) potentially related to treatment; 1.7% had serious AE; and 1.0% had treatment discontinuations due to AE. Limitations include missing data at later timepoints and the inclusion criteria limiting generalizability. In summary, this analysis of the ADDRESS‐J study showed that some patients with moderate or severe AD respond to conventional therapies, while others do not. For those with inadequately controlled moderate‐to‐severe AD, the newly emerged systemic agents, such as biologics, may provide a potential strategy for long‐term disease management.
Small farmlands can serve as open habitat for birds in subtropical cities of southern China
Authors: Lee Myung‐Bok
Published: June 2022

Greenspace or green cover is one of the major factors affecting urban avian diversity. In China, small farmlands producing vegetables are relatively common in cities. Although these farmlands could be a part of greenspaces, their habitat value for birds is rarely known. I investigated how these farmlands influenced winter bird community in two cities of southern China, using the multivariate latent variable model. I considered three green cover types: crop (mostly vegetables), weed (pioneer spontaneous vegetation), and wood (tree/shrub). I calculated the percentage of each green cover at local (50 m radius circular area) and landscape (500 m radius circular area) scales. Of 30 bird species, the abundance of 13 species decreased as crop cover decreased with increasing woody cover at the local scale, whereas the abundance of only two bird species increased with decreasing crop cover. Habitat preference of species mediated these responses, leading to a strong association between the open habit trait and the negative responses. Open habitat bird species richness was also negatively affected by decreasing local crop cover. Tree/shrub bird species richness showed a positive response to decreasing crop cover but the explanatory power of the local scale model was low. Variables at the landscape scale were rarely associated with species abundance or richness. These results suggest that small vegetable‐dominant farmlands can serve as open habitat for birds in urban areas where greenspace largely consists of tree/shrub vegetation. The results also indicate that urban bird diversity is more influenced by local habitat features than landscape‐scale features.
Floodplain managers' perceptions of community flood concern, mitigation, preparedness, and response in the United States
Authors: Tyler Jenna , Sadiq Abdul‐Akeem , Council Dontá , Noonan Douglas
Published: June 2022

Flooding causes more financial and physical destruction in the United States than any other natural hazard. To stem flood losses, local floodplain managers make decisions on how best to mitigate, prepare, and respond to flood hazards. Using quantitative and qualitative data gathered from interviews with 200 floodplain managers in the United States, this study explores the extent to which local communities are concerned about floods, perceptions of communities' ability to mitigate, prepare, and respond to floods, as well as the factors contributing to communities' perceptions of their ability to mitigate, prepare, and respond to floods. Findings indicate that floodplain managers generally perceived their communities to be very or somewhat concerned and prepared for floods. Floodplain managers also perceived their communities' ability to mitigate and respond to floods as being good. Lastly, the findings show that participation in the Federal Emergency Management Agency's Community Rating System was positively associated with floodplain managers' perceptions of their community's ability to mitigate, prepare, and respond to floods.
The relationship between emotional regulation of teachers and the participation of students with autism in inclusive primary and preschool schools
Authors: Hernández González Osvaldo , Spencer Contreras Rosario Elena , Sanz‐Cervera Pilar , Tárraga‐Mínguez Raúl
Published: June 2022

In this study, we used Gross's (2015) emotional regulation model to examine teachers' emotional regulation strategies and the relationship between this emotional regulation and the participation of students with ASD. The sample was selected using a non‐probabilistic technique (convenience) with a total of 131 Cuban teachers from primary schools and preschools participating. The results revealed significant differences in the emotional regulation strategies used by teachers which were associated with teaching stage and specific ASD training, with primary school teachers and those who had ASD training obtaining better results. In addition, a significant relationship was found between teachers using cognitive reappraisal of emotions and the participation of students with ASD in school. Practical implications, teacher training programs and lines of future research are discussed.
A case of fatal fulminant fat embolism syndrome following multiple fractures resulting from a fall
Authors: Hirata Yuichiro , Inokuchi Go , Tsuneya Shigeki , Hoshioka Yumi , Chiba Fumiko , Yoshida Maiko , Makino Yohsuke , Iwase Hirotaro
Published: June 2022

Fat embolism syndrome is a life‐threatening condition in which fatty substances enter the circulation and cause respiratory distress and neurological symptoms. It can occur following trauma and severe fat embolism occurring soon after trauma is known as fulminant fat embolism syndrome. Although fat staining of the lungs is helpful for diagnosing fat embolism syndrome at autopsy, clinical and other information is needed to determine the relationship between cause of death and the syndrome. In this report, we describe the macroscopic, microscopic, and computed tomography (CT) findings specific for fat embolism that were observed in a patient with fulminant fat embolism syndrome who died soon after the injury. An 85‐year‐old woman fell from a bath stretcher during assisted bathing and died 3 h later. Autopsy revealed fractures of the left femoral neck and other bones, as well as large amounts of fat‐like material in the right and left pulmonary arteries. Histological examination of the lung with Oil red O staining showed extensive fat vacuoles. Based on these findings and postmortem CT images of the fractures and fatty globules in the pulmonary arteries detected prior to death, the cause of death was determined to be blunt force trauma, with fat embolism syndrome playing a significant role. This case is an example of fulminant fat embolism, which can be fatal in a short period of time, and demonstrates that CT performed postmortem but before autopsy can be useful in detecting fat embolism syndrome due to trauma.
A framework for quantifying soundscape diversity using Hill numbers
Authors: Luypaert Thomas , Bueno Anderson S. , Masseli Gabriel S. , Kaefer Igor L. , Campos‐Cerqueira Marconi , Peres Carlos A. , Haugaasen Torbjørn
Published: June 2022

Soundscape studies are increasingly used to capture landscape‐scale ecological patterns. Yet, several aspects of soundscape diversity remain unexplored. Although some processes influencing acoustic niche usage may operate in the 24‐hr temporal domain, most acoustic indices only capture the diversity of sounds co‐occurring in sound files at a specific time of day. Moreover, many indices do not consider the relationship between the spectral and temporal traits of sounds simultaneously. To provide novel insights into landscape‐scale patterns of acoustic niche usage at broader temporal scales, we present a workflow to quantify soundscape diversity through the lens of trait‐based ecology.

Our workflow quantifies the diversity of sound in the 24‐hr acoustic trait space. We introduce the Operational Sound Unit (OSU), a unit of diversity measurement that groups sounds by their shared acoustic properties. Using OSUs and building on the framework of Hill numbers, we propose three metrics that capture different aspects of acoustic trait space usage: (i) soundscape richness, (ii) soundscape diversity and (iii) soundscape evenness. We demonstrate the use of these metrics by (a) simulating soundscapes to assess whether the indices possess a set of desirable behaviours and (b) quantifying soundscape richness and evenness along a gradient in species richness.

We demonstrate that (a) the indices outlined herein have desirable behaviours and (b) the soundscape richness and evenness are positively correlated with the richness of sound‐producing species. This suggests that more acoustic niche space is occupied when the species richness is higher. Additionally, species‐poor acoustic communities have a higher proportion of rare sounds and use the acoustic space less evenly.

Our workflow generates novel insights into acoustic niche usage at a landscape scale and provides a useful tool for biodiversity monitoring. Moreover, Hill numbers can also be used to measure the taxonomic, functional and phylogenetic diversity. Using a common framework for diversity measurement gives metrics a common behaviour, interpretation and standardised unit, thus ensuring comparisons between soundscape diversity and other metrics represent real‐world ecological patterns rather than mathematical artefacts stemming from different formulae.
Phenological growth stages of shea tree (Vitellaria paradoxa subsp. paradoxa) according to the BBCH scale
Authors: Konan Jacky Amenan , Kouakou Charles Konan , Allouan Kévin Philippe Jean , Coulibaly Abdoul‐Salam Krouholé , Djidji Hortense , Fondio Lassina
Published: June 2022

The shea tree is among the socio‐economically and environmentally most important plants in the Sudano‐Sahelian region of Africa. Shea butter is internationally valued for use in pharmaceutical, cosmetic and confectionary industries. Scaling and describing phenological growth stages is of great importance in crops management. However, such phenological scale is still lacking for shea tree. To fill this gap, we documented the different growth stages of shea tree by referencing to the Biologische Bundesantalt, Bundessortenamt und Chemische Industrie (BBCH) scale. Eight of the ten principal growth stages (0–9) and 43 secondary growth stages (0–9) were described in shea tree. Among the eight principal stages, four were related to reproductive phenophases: inflorescence emergence stage (5), flowering stage (6), fruit development stage (7), and fruit maturity stage (8). The remaining four principal stages concerned vegetative phenophases and contained: bud development stage (0), leaf development stage (1), shoot development stage (3), and senescence stage (9). Observations of shea tree phenophases depicted asynchronous growth patterns with overlapping secondary growth stages of different principal stages within an individual tree canopy at the same time. The proposed phenological growth scale specific to shea tree but compatible with other crops is a valuable contribution for the implementation of crops management protocols and the standardisation of research between different laboratories.
Prevalence and morphology of C‐shaped and non‐C‐shaped root canal systems in mandibular second molars
Authors: Fenelon T , Parashos P
Published: June 2022

Background

There are no cone‐beam computed tomography (CBCT)‐based data on the anatomy of mandibular second molars in an Australian population. This study investigated the prevalence and descending morphology of mandibular second molars with and without C‐shaped canals using retrospective analysis of CBCT scans.

Methods

Scans from 715 patients were screened for the presence of C‐shaped canals and assessed for cross‐sectional configuration at five axial levels. Non‐C‐shaped molars were assessed for other morphological characteristics. Data were modelled against patient, tooth and CBCT scan characteristics.

Results

A total of 1278 teeth from 657 patients were evaluated. The overall prevalence of C‐shaped canals was 13%. Cross‐sectional configuration of C‐shaped canals was variable, with an average of 2.8 unique cross‐sections per tooth. Non‐C‐shaped teeth were predominantly Vertucci Type II (60%) and Type IV (29%) configurations in mesial roots, and Type I (91%) in distal roots. Additional roots occurred in 4.3% of teeth and there was a significant association between radix paramolaris and distal root bifurcation (P < 0.001).

Conclusions

Cross‐sectional analysis confirmed the complexity and variability of C‐shaped canals. Clinicians should be cognizant of the prevalence and variability of C‐shaped root canal morphology and how this may affect endodontic treatment.
Circ_0060551 promotes the migration and invasion of cervical cancer by upregulating TPD52
Authors: Shi Qi , Ma Yuanyuan , Zhang Xiaojie , Yin Chunxia
Published: June 2022

Problem

Cervical cancer has been recognized as the second most common cancer in women worldwide. Previous studies have reported that some circular RNAs (circRNAs) can influence the progression of cervical cancer. However, more researches are still required to unveil the underlying mechanism of how circRNAs regulate the progression of such cancer. We aimed at unveiling the mechanism of how circ_0060551 effected the progression of cervical cancer.

Method of study

RT‐qPCR and western blot assays were used to detect the expression and protein levels. Mechanism experiments were conducted to investigate the relationship among circ_0060551, TPD52, miR‐520a‐5p and ELAVL1. Rescue assays were mainly carried out to verify how circ_0060551 influenced the migration and invasion of cervical cancer cells.

Results

According to the results, circ_0060551 was upregulated in cervical cancer cells and could promote the migration and invasion of cells via TPD52. In addition, circ_0060551 could up‐regulate TPD52 expression through a ceRNA model to target miR‐520a‐5p. Moreover, circ_0060551 could stabilize the mRNA expression of TPD52 via recruiting ELAVL1.

Conclusion

Our study proved that circ_0060551 could promote the migration and invasion of cervical cancer cells.
Sperm DNA damage in men with spinal cord injury: the relative incidence of single‐ and double‐strand DNA breaks
Authors: Gosálvez Jaime , Vargas‐Baquero Eduardo , López‐Fernández Carmen , Bartolomé‐Nebreda Javier , Fernández José Luís , Johnston Stephen
Published: June 2022

Background

Men with spinal cord injury (SCI) show a high proportion of sperm DNA damage in their ejaculate but the underlying pathology remains elusive.

Objective

To investigate the relative incidence of single (SSBs) and double‐strand DNA breaks (DSBs) and DNase activity in men with SCI.

Materials and methods

This study included ejaculates of 20 men with SCI and 27 normozoospermic (sperm donors). A TwoTails comet assay (TTComet) allowed visualization of three categories of sperm DNA damage corresponding to SSBs, DSBs and those with a combination of SSBs and DSBs, facilitating accurate calculation of the total proportion of SSBs and DSBs. A subset of 15 individuals (sperm donors and SCI patients) was used to test for DNase activity in the seminal plasma.

Results

While the proportion of DSBs in men with SCI (median‐57.5%) was higher (P = 0.000) than normozoospermic samples (median‐4.6%), the proportion of SSBs was higher (P = 0.022) in the normozoospermic ejaculates (median‐6.0%) compared to men with SCI (median‐2.5%). The relative proportion of the total DSBs with respect to the total SSBs was 3.3× in men with SCI but 0.9× in normozoospermic samples. We further confirmed the high DNase activity in the seminal plasma of men with SCI.

Discussion

The TTComet assay provided new insights to the pathology of sperm DNA in men with SCI and may have diagnostic value in developing sperm selection methodologies to reduce DSBs prior to ART.

Conclusion

Men with SCI are characterized by a high proportion of sperm with DSBs and high levels of DNase activity in the seminal plasma compared to normozoospermic men.
Efficacy and safety of new oral anticoagulants combined with antiplatelet drugs in the treatment of coronary heart disease: Systematic evaluation and meta‐analysis
Authors: Saiyitijiang Alimila , Aizezi Mayila , Zhao Ying , Gao Ying
Published: June 2022

Objective

To analyze the efficacy and safety of antiplatelet drugs combined with new oral anticoagulants (noac) in the treatment of coronary atherosclerotic heart disease (CAD).

Methods

The randomized controlled trials of noac combined with antiplatelet therapy in Cochrane, CNKI, PubMed, EMBASE, Wanfang, Google Scholar, and Baidu library were searched using the literature database. Two researchers independently searched and screened to ensure the consistency of the results, and the literature was summarized and analyzed by Revman 5.3 software.

Results

Five research results were included. The results showed that the incidence of mace [95% CI 0.75–0.95, or = 0.84,p = .04], the incidence of major and minor bleeding [95% CI 1.25–5.16, or = 2.54,p = .01], the mortality of cardiovascular disease [95% CI 0.78–0.96, or = 0.86, p = .05], the total mortality [95% CI 0.79–0.95, or = 0.87, p = .003], and the incidence of myocardial infarction in patients with CAD treated with noac and antiplatelet drugs [95% CI 0.77–0.95, or = 0.85, p = .004] was lower than that treated with antiplatelet drugs alone, and the difference was statistically significant (p < .05); the incidence of fatal bleeding [95% CI 0.81–2.08, or = 1.30, p = .28], the incidence of stroke [95% CI 0.50–1.03, or = 0.71, p = .07], and the incidence of intracranial hemorrhage [95% CI 1.02–2.56, or = 1.61, p = .06]. There was no significant difference with antiplatelet drugs alone (p > .05).

Conclusion

Noac combined with antiplatelet drugs can reduce mace, total mortality, the incidence of myocardial infarction, and cardiovascular mortality in patients with CAD, but may increase the risk of bleeding.
Mitigation of postoperative urinary retention among total joint replacement patients using the ERAS protocol and applying risk‐stratified catheterization
Authors: Peng Hui‐ming , Tong Bing‐du , Li Ye , Wang Wei , Li Wen‐li , Gao Na
Published: June 2022

Backgrounds

We intended to identify the incidence and risk factors (RFs) for Postoperative urinary retention (POUR) after applying a risk‐stratified catheterization optimization method in enhanced recovery after surgery (ERAS)‐total joint arthroplasty (TJA).

Methods

A total of 381 patients were prospectively monitored for POUR. POUR diagnosis was done by a perioperative specialist. Data on potential risk factors (RFs) for POUR were accumulated. Univariate analysis (UA) was conducted to identify possible indicators of POUR, followed by multivariate analysis (MA) of identified indicators.

Results

POUR occurred in 5.5% of cases, including 8 (3.4%) patients underwent total knee arthroplasty and 13 (10.4%) patients underwent total hip arthroplasty. In UA, age, sex, American Society of Anesthesiologists (ASA) score, and the type of operation were significantly different on UA (P = 0.046, P = 0.022, P = 0.000 and P = 0.049, respectively). Other additional predictors, including body mass index (BMI), international prostate symptom score (IPSS) score, preoperative haemoglobin (Hb), duration of operation, estimated intraoperative blood loss, intraoperative fluid volume, fluid infusion volume within 24 h postoperatively were not associated with POUR (P > 0.05). MA results demonstrated that age, ASA score, type of operation and standard intraoperative placement of an indwelling bladder catheter (SIP‐IBC) were strongly associated with POUR development risk (P < 0.05).

Conclusion

Overall, we had a low POUR incidence in our study cohort. However, with the shift from non‐ERAS TJA to ERAS TJA protocol, it is crucial to closely monitor the male gender, advanced age, THA and SIP‐IBC, as these variables can markedly enhance POUR risk.
Can acute exercise be more pleasant? Using audiovisual stimuli: A meta‐analysis
Authors: Wang Yu‐Bu
Published: June 2022

This meta‐analytic study aimed to examine the effects of audiovisual stimuli on affective responses during and after exercise and their moderators. A total of 296 effect sizes (Hedge's g) were extracted from 46 independent studies covering 1292 participants. Meta‐analysis was performed using Comprehensive Meta‐Analysis Version 3.3, and potential moderating variables were analysed using univariate meta‐regression models. Audiovisual stimuli increased affective valence during (g = 0.793, 95% CI [0.666, 0.920]) and after exercise (g = 0.792, 95% CI [0.567, 1.016]), and arousal during (g = 0.920, 95% CI [0.742 1.097]) and after exercise (g = 0.666, 95% CI [0.390, 0.962]). There may be publication bias in the meta‐analysis, but the main findings are still valid. The type of audiovisual stimuli (audio‐video > audio or video), exercise habits (active > not reported), and exercise intensities (self‐selected > imposed) moderated the effects. In conclusion, the application of audiovisual stimuli during exercise can elicit positive affective responses. These results provide a viable intervention strategy for exercise and health practitioners to reduce the number of physically inactive individuals and improve exercise compliance and adherence.
Feasibility of delayed anastomosis for long gap esophageal atresia in the neonatal period using internal traction and indocyanine green‐guided near‐infrared fluorescence
Authors: Onishi Shun , Muto Mitsuru , Yamada Koji , Murakami Masakazu , Kedoin Chihiro , Nagano Ayaka , Matsui Mayu , Sugita Koshiro , Yano Keisuke , Harumatsu Toshio , Yamada Waka , Masuya Ryuta , Kawano Takafumi , Ieiri Satoshi
Published: June 2022

Introduction

Management of neonates with long gap esophageal atresia (LGEA) is one of the most challenging situations facing pediatric surgeons. Delayed anastomosis after internal traction for esophageal lengthening was reported as a useful technique for long gap cases. Additionally, the use of near‐infrared (NIR) fluorescence imaging with indocyanine green (ICG) has gained popularity in pediatric surgery, especially for blood perfusion validation. We report a novel technique for safe and secure anastomosis for LGEA in the neonatal period using internal traction and ICG‐guided NIR fluorescence.

Patient and Surgical Technique

A pregnant woman with polyhydramnios was admitted to the department of obstetrics in our hospital. At 29 weeks of gestation, ultrasound showed mild polyhydramnios and absence of the fetal stomach. A male neonate was born at 38 weeks of gestation with 21 trisomy. EA (Gross type A) was diagnosed based on an X‐ray study that showed the absence of gastric bubble with a nasogastric tube showing the “coil‐up” sign. Thoracoscopic internal traction and laparoscopic gastrostomy were performed on day 4 after birth. We confirmed the distance between the upper pouch and lower pouch on X‐ray. On day 16 after birth, thoracoscopic anastomosis was performed. We successfully performed esophageal anastomosis without tearing the esophageal wall. Blood perfusion of the upper and lower pouch was validated after anastomosis using ICG‐guided NIR fluorescence.

Conclusion

Delayed anastomosis for LGEA in the neonatal period using internal traction and ICG‐guided NIR fluorescence is safe and feasible.
Estimates of genetic parameters for adenosine triphosphate‐related compounds at different aging periods and NT5E genotypes in Japanese Black beef
Authors: Komatsu Tomohiko , Toita Tsuyoshi , Uemoto Yoshinobu
Published: June 2022

Previous studies on Japanese Black beef showed that single nucleotide polymorphisms in the ecto‐5′‐nucleotidase (NT5E) gene affected the degradation rate of inosine 5′‐monophosphate (IMP), which has contributed to the umami taste, especially between Postmortem Days 4 and 7. Therefore, this study estimated the genetic parameters of IMP and its degradation products on Postmortem Days 4 and 7 using the model with or without the NT5E genotype. The heritability estimates of IMP on Postmortem Days 4 and 7 were moderate by the model without the NT5E genotype (0.44 and 0.32, respectively). When the NT5E genotype was included in the model, the heritability of IMP on Postmortem Day 4 did not change, whereas that on Day 7 decreased from 0.32 to 0.08. The genetic correlation of IMP between Postmortem Days 4 and 7 was highly positive using the model with the NT5E genotype. Regarding the estimated breeding values (EBVs) of IMP, the ranking of EBVs among NT5E genotypes was not changed between Postmortem Days 4 and 7, when the model with the NT5E genotype was used. The study suggested that the model including NT5E genotype would allow for appropriate genetic parameter estimation and breeding value evaluation in adenosine triphosphate‐related compounds (ATPRCs) under different aging periods.
Do we become better prescribers after graduation: A 1‐year international follow‐up study among junior doctors
Authors: Donker Erik M. , Brinkman David J. , van Rosse Floor , Janssen Ben , Knol Wilma , Dumont Glenn , Jorens Philippe G. , Dupont Alain , Christiaens Thierry , van Smeden Jeroen , de Waard‐Siebinga Itte , Peeters Laura E. J. , Goorden Ronald , Hessel Marleen , Lissenberg‐Witte Birgit , Richir Milan , van Agtmael Michiel A. , Kramers Cornelis , Tichelaar Jelle ,   the Education committee of the Dutch Society for Clinical Pharmacology and Biopharmacy
Published: June 2022

Aim

The aim of this study was to investigate how the prescribing knowledge and skills of junior doctors in the Netherlands and Belgium develop in the year after graduation. We also analysed differences in knowledge and skills between surgical and nonsurgical junior doctors.

Methods

This international, multicentre (n = 11), longitudinal study analysed the learning curves of junior doctors working in various specialties via three validated assessments at about the time of graduation, and 6 months and 1 year after graduation. Each assessment contained 35 multiple choice questions (MCQs) on medication safety (passing grade ≥85%) and three clinical scenarios.

Results

In total, 556 junior doctors participated, 326 (58.6%) of whom completed the MCQs and 325 (58.5%) the clinical case scenarios of all three assessments. Mean prescribing knowledge was stable in the year after graduation, with 69% (SD 13) correctly answering questions at assessment 1 and 71% (SD 14) at assessment 3, whereas prescribing skills decreased: 63% of treatment plans were considered adequate at assessment 1 but only 40% at assessment 3 (P < .001). While nonsurgical doctors had similar learning curves for knowledge and skills as surgical doctors (P = .53 and P = .56 respectively), their overall level was higher at all three assessments (all P < .05).

Conclusion

These results show that junior doctors' prescribing knowledge and skills did not improve while they were working in clinical practice. Moreover, their level was under the predefined passing grade. As this might adversely affect patient safety, educational interventions should be introduced to improve the prescribing competence of junior doctors.
Tracking what went where across toddlerhood: Feature‐location bound object representations in 2‐ to 3‐year‐olds' working memory
Authors: Kibbe Melissa M. , Applin Jessica B.
Published: June 2022

Two experiments examined the development of the ability to encode, maintain, and update integrated representations of occluded objects' locations and featural identities in working memory across toddlerhood. Sixty‐eight 28‐ to 40‐month‐old US toddlers (13 Asian or Pacific Islander, 6 Black, 48 White, 1 multiracial; 40 girls; tested between February 2015 and July 2017) tracked the locations of different color beads that were hidden simultaneously (Experiment 1) or sequentially (Experiment 2). Toddlers' ability to reliably store feature‐location bound object representations in working memory varied as a function of age, memory load, and task demands. These results bridge a developmental gap between infancy and early childhood and provide new insights into sources of limitation and developmental change in children's early object representational capacities.
Are children in foster care in better psychological health than children in institutions? What factors influence the outcome?
Authors: Chartier Stéphanie , Blavier Adélaïde
Published: June 2022

The aim of this study was to compare the psychological health of children in foster care with that of children in institutional care. Social workers were asked to assess the psychological health of the children as well as several other criteria on the basis of an analysis grid. Our sample consisted of 568 children placed in foster care and 661 children placed in institutions. Our results show that children in care who lived longer with their birth parents have a lower psychological health. Furthermore, the psychological health of children in residential care is lower than children placed in foster families. As children in institution are placed later than children in foster families, this may partially explain the lower psychological health of children in residential care. As a result, children in residential care have experienced more abuse and neglect and witnessed more domestic violence than children in foster care. In addition, children in residential care have more poor‐quality contacts with their birth parents than children in foster family. These contacts negatively influence their psychological health. Finally, the factor that most influences the psychological health of children in care is the quality of the relationship with the people who care for them on a daily basis. Again, children placed in foster families have better‐quality relationships with their foster families than children placed in institutions.
Erythropoietin promotes the differentiation of fetal neural stem cells into glial cells via the erythropoietin receptor‐β common receptor/Syne‐1/H3K9me3 pathway
Authors: Yang Zhen‐Hong , Zhang Si‐Jia , Zhao Hai‐Ping , Li Fang‐Fang , Tao Zhen , Luo Yu‐Min , Wang Rong‐Liang
Published: June 2022

Aims

To investigate the effect of erythropoietin (EPO) on the differentiation of neural stem cells (NSCs)/neural progenitors (NPs) in the treatment of hypoxic–ischemic injury and its potential mechanisms.

Methods

Fetal NSCs/NPs were treated with EPO after oxygen and glucose deprivation/reoxygenation (OGD/R). Cell viability, proliferation, and differentiation of NSCs/NPs were detected by CellTiter‐Glo, Edu assay, flow cytometry, and quantitative real‐time PCR (qPCR). Immunofluorescence staining, co‐immunoprecipitation (Co‐IP), and western blotting were used to test the existence of EPO receptor/β common receptor (EPOR/βCR) heterodimer on NSCs/NPs and the possible pathway.

Results

EPO treatment at different time points increased cell viability without affecting proliferation. EPO treatment immediately after OGD/R promoted oligodendrocyte and astrocyte differentiation, while decreasing neuronal differentiation of NSCs/NPs. EPOR/βCR heterodimer existed on the cell surface of the fetal cortical NSCs/NPs, EPO treatment significantly increased the mRNA expression of βCR and elevated the correlation between EPOR and βCR levels. In addition, mass spectrometry analysis identified Syne‐1 as a downstream signaling molecule of the EPOR/βCR heterodimer. Immunofluorescence staining and western blotting indicated that the βCR/Syne‐1/H3K9me3 pathway was possibly involved in the differentiation of fetal neural stem cells into the glial cell effect of EPO.

Conclusion

EPO treatment immediately after OGD/R could not facilitate fetal NSCs/NPs neurogenesis but promoted the formation of the EPOR/βCR heterodimer on fetal NSCs/NPs, which mediates its function in glial differentiation.
A closer look at allergic contact dermatitis caused by topical ophthalmic medications
Authors: Alves Pedro Botelho , Figueiredo Ana Carolina , Codeço Carlos , Regateiro Frederico S. , Gonçalo Margarida
Published: June 2022

Background

Allergic contact dermatitis caused by topical ophthalmic medications (OftACD) is frequently difficult to confirm with patch testing and, therefore, it is considered uncommon.

Methods

We collected retrospective data from a cohort of 65 patients with suspected OftACD patch tested in our Dermatology Unit (2005–2021) according to ESCD guidelines, using a series of topical drugs and excipients (Chemotechnique Diagnostics), including betaxolol and timolol 5% pet. kindly supplied by the pharmaceutical industry. Also, frequently used ophthalmic medications as well as patient's own products were also patch tested ‘as is’ in most patients.

Results

Positive patch tests to ophthalmic medications occurred in 44 patients (67.7%) (38F/6M; mean age 63.1 years), with 102 positive reactions. Most positive reactions were associated with active ingredients (n = 56), especially aminoglycoside antibiotics (n = 27), followed by excipients (n = 24) such as sodium metabisulfite (n = 7). There were also positive reactions to topical products tested ‘as is’ (n = 22), mostly containing beta‐blockers, but only five of these reacted to the active ingredient.

Discussion

This study reinforces previous findings in OftACD, such as older age of onset, and the importance of antibiotics, contrasting with the progressively lower prevalence of excipients. In addition, it helps raising awareness for the sensitization to beta‐blockers, which is probably underestimated. Patch test preparations for the diagnosis of OftACD may require protocol optimization.
Differences in the stemness characteristics and molecular markers of distinct human oral tissue neural crest‐derived multilineage cells
Authors: Abe Shigehiro , Kaida Atsushi , Kanemaru Kazunori , Nakazato Keiichiro , Yokomizo Naoko , Kobayashi Yutaka , Miura Masahiko , Miki Toshio , Hidai Chiaki , Kitano Hisataka , Yoda Tetsuya
Published: June 2022

Objectives

Although multilineage cells derived from oral tissues, especially the dental pulp, apical papilla, periodontal ligament, and oral mucosa, have neural crest‐derived stem cell (NCSC)‐like properties, the differences in the characteristics of these progenitor cell compartments remain unknown. The current study aimed to elucidate these differences.

Material and methods

Sphere‐forming apical papilla‐derived cells (APDCs), periodontal ligament‐derived cells (PDLDCs), and oral mucosa stroma‐derived cells (OMSDCs) from the same individuals were isolated from impacted developing teeth. All sphere‐forming cells were characterized through biological analyses of stem cells.

Results

All sphere‐forming cells expressed neural crest‐related markers. The expression of certain tissue‐specific markers such as CD24 and CD56 (NCAM1) differed among tissue‐derived cells. Surprisingly, the expression of only CD24 and CD56 could be discriminated in human tissues. Although APDCs and PDLDCs exhibited greater mineralized cell differentiation than OMSDCs, they exhibited poorer differentiation into adipocytes in vitro. In immunocompromised mice, APDCs formed hard tissues better than PDLDCs and OMSDCs.

Conclusions

Although cells with NCSC‐like properties present the same phenotype, they differ in the expression of certain markers and differentiation abilities. This study is the first to demonstrate the differences in the differentiation ability and molecular markers among multilineage human APDCs, PDLDCs, and OMSDCs obtained from the same patients, and to identify tissue‐specific markers that distinguish tissues in the developing stage of the human tooth with immature apex.