bluuebunny/crossref_metadata_2025_split huggingface dataset:
Phenotyping in acute respiratory distress syndrome: state of the art and clinical implications
Authors: Alipanah Narges , Calfee Carolyn S. 
Published: October 2021

Purpose of review
Decades of research in acute respiratory distress syndrome (ARDS) have led to few interventions that impact clinical outcomes. The pandemic of patients with ARDS due to the novel SARS-CoV-2 infection has stressed the need for more effective therapies in ARDS. Phenotyping may enable successful trials and precision therapeutics in this patient population.

Recent findings
Clinical phenotypes that group patients by shared cause, time-course or radiographic presentation are of prognostic value, but their use is limited by misclassification. Physiological phenotypes, including the P/F ratio, ventilatory ratio and dead space fraction, predict poor outcomes but can rapidly change, making them unstable over time. Biologic phenotypes have prognostic value with composite clinical and biomarker sub-phenotypes additionally impacting treatment response but are yet to be prospectively validated.

Summary
Although much progress has been made in ARDS phenotyping, implementation of precision medicine practices will depend on conducting phenotype-aware trials using rapid point of care assays or machine learning algorithms. Omics studies will enhance our understanding of biologic determinants of clinical outcomes in ARDS sub-phenotypes. Whether biologic ARDS sub-phenotypes are specific to this syndrome or rather more broadly identify endotypes of critical illness remains to be determined.
Targeting the cluster of differentiation 47/signal-regulatory protein alpha axis in myeloid malignancies
Authors: Wang Chen , Sallman David A. 
Published: October 2021

Purpose of review
The antitumor activity of macrophages is regulated by a balance of prophagocytic and antiphagocytic signals. Cluster of differentiation 47 (CD47), the dominant macrophage immune checkpoint (‘do not eat me’ signal), interacts with its receptor signal-regulatory protein alpha (SIRPα) to suppress phagocytic activities. This axis plays a pivotal role in immune evasion in myeloid malignancies as well as multiple cancers providing strong rationale for therapeutic exploitation.

Recent findings
Preclinical studies have revealed overexpression of CD47 on leukemic stem cells and myeloblasts from patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML), which contributes to immune surveillance evasion and is associated with poor outcomes. Blockade of CD47 with different approaches has demonstrated proof-of-concept antitumor activities mainly through phagocytic clearance. Early phase clinical trials combining the anti-CD47 mAb magrolimab with the hypomethylating agent azacitidine have showed synergistic activities, deep and durable responses, as well as a tolerable safety profile in these patients, including those with TP53 mutations.

Summary
Targeting CD47/SIRPα axis, in combination with other therapeutic agents, represents a promising treatment approach for patients with myeloid malignancies, particularly the challenging TP53-mutated subgroup.
Versatility of the subscapular system of flaps in head and neck oncologic reconstruction
Authors: Deganello Alberto , Rampinelli Vittorio , Gualtieri Tommaso , Piazza Cesare 
Published: October 2021

Purpose of review
This review analyzes the different ways of applying the subscapular system of flaps (SSSF) as a convenient and versatile solution for a large variety of head and neck oncologic defects.

Recent findings
The ventral approach permits safe and efficient harvest of various chimeric SSSF in a supine position, thus allowing simultaneous flap preparation and tumor ablation. Conformational studies have revealed how similar the tip of the scapula is to the hard palate in terms of dimensions, shape, and conformation. This has led to favor horizontal placement of the scapular tip for palate reconstruction in most instances, addressing the vertical extension of the postmaxillectomy defect using denuded bony grafts surrounded by well vascularized chimeric muscular components.

Summary
The SSSF possesses an unparalleled versatility to efficiently address small-medium sized soft tissue defects up to vast and complex composite resections. The chimeric components of these flaps benefit from a considerable independency provided by the length of the named arteries arising from the thoracodorsal pedicle, offering a high degree of freedom to accomplish the required in-setting. This reconstructive option should be implemented in every head and neck surgical team and offered to suitable patients.
Burnout in Rheumatologists in Latin America
Authors: Intriago Maria , Maldonado Genessis , Soriano Enrique , Toro Carlos , Moreno Letty , Ríos Carlos 
Published: October 2021

Background
Rheumatology is considered a low-risk specialty, but studies have shown a prevalence of burnout between 42% and 51%.

Objectives
The aim was to determine the prevalence of burnout in rheumatologists in Latin America and the factors associated with it.

Methods
Cross-sectional study based on a survey completed through Google Forms platform that was sent by the national rheumatology associations of Latin America. Burnout was assessed with the Maslach Burnout Inventory. Data were analyzed using the statistical program SPSS v.22.

Results
Two hundred ninety-seven rheumatologists from 15 countries were included, mainly Argentina (28.3%), Brazil (26.3%), and Mexico (12.8%). The majority were women 62%, 42.4% worked in public hospitals with an average of 40.1 ± 14.2 hours per week; 31.3% did research, 13.1% clinical trials, 56.6% teaching, and 42.8% administrative work; 36% received an annual income less than $25,000; 56.6% had burnout in at least 1 dimension. Only 20.2% thought they had burnout, 9.1% were currently receiving professional help, and 15.8% had sought help in the past; 72.1% said they were willing to participate in a program to reduce burnout. The rheumatologists with burnout were younger than those without burnout (46.5 vs 49.9 years, p = 0.015).

Conclusions
Burnout affects near half of rheumatologists in Latin America and was associated with younger age, long working hours, low satisfaction, less happiness, higher Patient Health Questionnaire–9, suicidal thoughts, anxiety, income, presence of comorbidities, and low self-esteem.
Revisited Arterial Supply of the Anterior Ear
Authors: Kim Young Soo , Kim Hee-Jin 
Published: October 2021

Background
Since arterial supply of the anterior ear was described in 1992 by Park et al, various anatomical studies and surgical techniques have been published in the literatures. Although anatomic studies about the vascular pattern of the ear have been previously reported, most were incomplete to understand the vascular anatomy of the ear and its surgical outcomes. In this report, the authors defined further detailed vascular pattern of the arterial networks and of the main perforators of the anterior ear.

Methods
The authors dissected in a total of 11 auricles that had been fixed in 10% formalin solution. Prior to dissection, a red latex solution was injected into the common carotid artery. The anteroauricular and postauricular skin was dissected to expose the arterial network under ×10 microscope magnification.

Results
There are 2 arterial networks in the anteroauricular surface of the ear: triangular–scapha fossa and concha network. In this study, triangular-scapha fossa network has 2 vascular patterns by a dominant arterial supply: the superficial temporal artery (STA) type (6/11, 54.5%) and the posterior auricular artery (PAA) type (5/11, 45.4%). The STA type is distributed by a subbranch of the ascending helical artery of the STA, whereas the dominant arterial supply of the PAA type is a perforator of the triangular fossa from the PAA. We describe an important inflow to the triangular-scapha fossa network as blood supply from the middle division of the PAA, which directly emerges from the posterior to the anterior surface over the cartilage border at midhelix.

Conclusions
The detailed vascular anatomy of this report allows surgeons to perform surgical procedures safely and to develop various flaps in the field of the ear reconstruction.
Incidence of New-Onset Obstructive Sleep Apnea After Posterior Flap Pharyngoplasty in Children
Authors: Trabelsi Ines , Amaddeo Alessandro , Michel Benoit , Khirani Sonia , Picard Arnaud , Fauroux Brigitte 
Published: October 2021

Introduction
Obstructive sleep apnea (OSA) is a well-recognized complication of velopharyngeal insufficiency (VPI) surgery, but studies assessing OSA by means of a respiratory polygraphy (PG) are scarce. The aim of the study was to evaluate the incidence of new-onset OSA after posterior flap pharyngoplasty (PFP).

Materials
The postoperative PG of children with VPI who had a normal preoperative PG were analyzed.

Results
Eighteen patients (mean age, 9.8 ± 4.8 years; Pierre Robin sequence [n = 5], isolated cleft palate [n = 7], 22q11 deletion [n = 3], and 3 other diagnoses) were included in the study. Mean delay between surgery and the postoperative PG was 11.5 ± 13.5 months. Two patients (11%) developed severe OSA after PFP. One patient with 22q11 deletion developed overt OSA symptoms immediately after surgery with an apnea-hypopnea index (AHI) of 39 events per hour, requiring continuous positive airway pressure (CPAP) therapy. Obstructive sleep apnea improved spontaneously after 10 months, with an AHI of 2 events/h after CPAP weaning. The second patient had a cleft palate associated with a fetal alcohol syndrome and developed OSA symptoms after surgery with an AHI of 18 events/h requiring CPAP therapy. He could be weaned from CPAP 6 months later after a complete section of the pharyngeal flap with an AHI of 6 events/h during spontaneous breathing.

Conclusions
New-onset OSA after PFP in children with VPI who had a normal preoperative PG was uncommon (11%) in the present cohort.
Context Matters! Depression following childbirth or a chronic disease diagnosis shows specific risk factor profiles
Authors: Jermy Bradley S , Hagenaars Saskia , Coleman Jonathan RI , Vassos Evangelos , Lewis Cathryn M 
Published: October 2021

AbstractProgress towards understanding the etiology of major depression (MD) is compromised by its clinical heterogeneity. The variety of contexts underlying the development of a major depressive episode may contribute to such heterogeneity. Here, we aimed to compare risk factor profiles of three subgroups of MD according to episode context.Using self-report questionnaires and administrative records from the UK Biobank, we characterised three contextual subgroups of MD: postpartum depression (3,581 cases), depression following diagnosis of a chronic disease (409 cases) and a more typical (named heterogeneous) MD phenotype excluding the two prior contexts (34,699 cases). Controls with the same exposure were also defined. We tested each subgroup for association with MD polygenic risk scores (PRS) and other risk factors previously associated with MD (bipolar disorder PRS, neuroticism, reported trauma in childhood and adulthood, socioeconomic status, family history of depression, education).MD polygenic risk scores were associated with all subgroups, however, postpartum depression cases had higher PRS than heterogeneous MD cases (OR = 1.06, 95% CI: 1.02 – 1.10). Relative to heterogeneous depression, postpartum depression was more weakly associated with adulthood trauma and neuroticism. Relative to heterogeneous depression, depression following diagnosis of a chronic disease did not have higher MD polygenic risk scores but had weaker associations with neuroticism and reported trauma in adulthood and childhood.The observed differences in risk factor profiles according to the context of a major depressive episode help provide insight into the heterogeneity of depression. Future studies dissecting such heterogeneity could help reveal more refined etiological insights.
The hallucinogenic serotonin2A receptor agonist, DOI, promotes CREB-dependent gene expression of specific plasticity-associated genes in the rodent neocortex
Authors: Desouza Lynette A. , Benekareddy Madhurima , Fanibunda Sashaina E. , Mohammad Farhan , Gur Tamar , Blendy Julie A. , Vaidya Vidita A. 
Published: October 2021

AbstractPsychedelic compounds that target the 5-HT2A receptor are reported to evoke psychoplastogenic effects, including enhanced dendritic arborization and synaptogenesis. Transcriptional regulation of neuronal plasticity-associated genes is implicated in the cytoarchitectural effects of serotonergic psychedelics, however the transcription factors that drive this regulation are poorly elucidated. Here, we addressed the contribution of the transcription factor cAMP response element binding protein (CREB) in the regulation of neuronal plasticity-associated genes by the hallucinogenic 5-HT2A receptor agonist, DOI. In vitro studies with rat cortical neurons indicated that DOI enhances the phosphorylation of CREB (pCREB) through the MAP kinase and CaMKII pathways, with both cascades contributing to the DOI-evoked upregulation of Arc, Bdnf1, Cebpb and Egr2 expression, whilst the upregulation of Egr1 and cFos mRNA involved the MAP kinase and CaMKII pathway respectively. We observed a robust DOI-evoked increase in the expression of several neuronal plasticity-associated genes in the rat neocortex in vivo. Further, 5-HT2A receptor stimulation enhanced pCREB enrichment at putative cAMP response element (CRE) binding sites in the Arc, Bdnf1, Cebpb, cFos, but not Egr1 and Egr2, promoters in the rodent neocortex. The DOI-mediated transcriptional induction of Arc, cFos and Cebpb was significantly attenuated in the neocortex of CREB deficient (CREBαδ KO) mice. Collectively, these results indicate that the hallucinogenic 5-HT2A receptor agonist DOI leads to a rapid transcriptional upregulation of several neuronal plasticity-associated genes, with a subset of them exhibiting a CREB-dependent regulation. Our findings raise the intriguing possibility that similar to slow-acting classical antidepressants, rapid-action serotonergic psychedelics that target the 5-HT2A receptor may also recruit the transcription factor CREB to enhance the expression of neuronal plasticity-associated genes in the neocortex, which could in turn contribute to the rapid psychoplastogenic changes evoked by these compounds.
Lift the Veil of Breast Cancers Using Four or Fewer Critical Genes
Authors: Zhang Zhengjun 
Published: October 2021

AbstractTackling breast cancer problems is like mastering a puzzle, and the mystery is not yet solved. Reported key genes in the literature could not be confirmed whether they are vital to breast cancer formations due to lack of convincing accuracy, although they may be biologically directly related to breast cancer based on present biological knowledge. It is hoped vital genes can be identified with the highest possible accuracy, e.g., 100% accuracy and convincing causal patterns beyond what has been known in breast cancer. One hope is that finding gene-gene interaction signatures and functional effects may solve the puzzle. This research uses a recently developed competing linear factor analysis method in differentially expressed gene detection to advance the study of breast cancer formation to its deepest root level as deep as possible. Surprisingly, three genes are detected to be differentially expressed in TNBC, and non-TNBC (Her2, Luminal A, Luminal B) samples with 100% sensitivity and 100% specificity in one study of triple-negative breast cancers (TNBC, with 54675 genes and 265 samples). These three genes show a clear signature pattern of how TNBC patients can be grouped. For another TNBC study (with 54673 genes and 66 samples), four genes bring the same accuracy of 100% sensitivity and 100% specificity. Four genes are found to have the same accuracy of 100% sensitivity and 100% specificity in one breast cancer study (with 54675 genes and 121 samples), and the same four genes bring an accuracy of 100% sensitivity and 96.5% specificity in the fourth breast cancer study (with 60483 genes and 1217 samples.) These results show the four-gene-based classifiers are robust and accurate. The detected genes naturally classify patients into subtypes, e.g., seven subtypes. These findings demonstrate the clearest gene-gene interaction patterns and functional effects with the smallest numbers of genes and the highest accuracy compared with findings reported in the literature. The four genes are considered to be essential for breast cancer studies and practice. They can provide focused, targeted researches and precision medicine for each subtype of breast cancer. New breast cancer disease types may be detected using the classified subtypes, and hence new effective therapies can be developed.
Heterogeneous Tfh cell populations that develop during enteric helminth infection predict the quality of type 2 protective response
Authors: Zaini Aidil , Dalit Lennard , Sheikh Amania A. , Thiele Daniel , Zhang Yan , Runting Jessica , Rodrigues Grace , Ng Judy , Bramhall Michael , Scheer Sebastian , Hailes Lauren , Groom Joanna R. , Good-Jacobson Kim L. , Zaph Colby 
Published: October 2021

AbstractT follicular helper (Tfh) cells are an important component of the germinal centre (GC)-mediated humoral immunity. Yet, how regulation of Tfh- GC responses impacts on effective responses to helminth infection are poorly understood. Here we show that chronic helminth Trichuris muris infection fails to induce Tfh-GC B cell responses, with Tfh cells expressing T-bet and IFN-γ. In contrast, Tfh cells that express GATA-3 and IL-4 dominate responses to an acute, resolving infection. Accordingly, heightened expression and increased chromatin accessibility of Th1- and Th2 cell-associated genes is observed in chronic and acute induced Tfh cells, respectively. However, both acute and chronic Tfh cell populations retained the capacity to produce IL-21 in spite of the Th-biased response. Blockade of Tfh-GC interactions impaired type 2 immunity, highlighting the protective role of GC-dependent Th2-like Tfh cell responses against helminths. Collectively, these results provide new insights into the protective roles of Tfh-GC responses and identify distinct transcriptional and epigenetic features of Tfh cells that emerge during resolving or chronic helminth infections.Author summaryAbout a quarter of the world population is afflicted with parasitic worm infection. Although deworming drugs can reduce the levels of the infection, they fail to prevent reinfections. Therefore, the most sustainable goal is to develop vaccines against human helminth parasites, which has been extremely challenging due to the lack of understanding of host-parasite interactions. While the protective roles of T helper 2 (Th2) cells are well established, the regulation of T follicular helper (Tfh) cells and their roles during helminth infection remain poorly defined. In this study, we describe the differential regulation of Tfh cell responses during chronic non-protective vs acute protective responses during helminth infection. We show that Tfh cells during chronic infection are rare and have strikingly different characteristics to acute-induced Tfh cells, which appear to be more like Th2 cells. Specifically, we show that blockade of Th2-like Tfh cell response during acute infection results in the host failing to expel the worms. Our study identifies that Tfh cell populations that emerge during chronic and acute infection are strikingly heterogeneous and critically important in mediating protective immune responses against helminths.
Evidence for a conserved queen-worker genetic toolkit across slave-making ants and their ant hosts
Authors: Feldmeyer B. , Gstöttl C. , Wallner J. , Jongepier E. , Séguret A. , Grasso D.A. , Bornberg-Bauer E. , Foitzik S. , Heinze J. 
Published: October 2021

AbstractThe ecological success of social Hymenoptera (ants, bees, wasps) depends on the division of labour between the queen and workers. Each caste is highly specialised in its respective function in morphology, behaviour and life-history traits, such as lifespan and fecundity. Despite strong defences against alien intruders, insect societies are vulnerable to social parasites, such as workerless inquilines or slave-making (dulotic) ants. Here, we investigate whether gene expression varies in parallel ways between lifestyles (slave-making versus host ants) across five independent origins of ant slavery in the“Formicoxenus-group” of the ant tribe Crematogastrini. As caste differences are often less pronounced in slave-making ants than non-parasitic ants, we also compare the transcriptomes of queens and workers in these species. We demonstrate a substantial overlap in expression differences between queens and workers across taxa, irrespective of lifestyle. Caste affects the transcriptomes much more profoundly than lifestyle, as indicated by 37 times more genes being linked to caste than to lifestyle and by multiple caste-associated gene modules with strong connectivity. However, several genes and one gene module are linked to the slave-making lifestyle across the independent origins, pointing to some evolutionary convergence. Finally, we do not find evidence for an interaction between caste and lifestyle, indicating that caste differences remain consistent even when species switch to a parasitic lifestyle. Our findings are a strong indication for the existence of a core set of genes whose expression is linked to the queen and worker caste in this ant taxon, supporting the “genetic toolkit” hypothesis.
Locational memory of macrovessel vascular cells is transcriptionally imprinted
Authors: Spanjersberg Talitha C.F. , Oosterhoff Loes A. , Kruitwagen Hedwig S. , van den Dungen Noortje A.M. , Harakalova Magdalena , Mokry Michal , Spee Bart , van Steenbeek Frank G. 
Published: October 2021

AbstractThe locational predisposition of vascular pathologies illustrates the need for a better insight into vascular heterogeneity. To investigate the transcriptomic basis of angiodiversity, we isolated and analyzed transcriptomes from endothelial cells and vascular smooth muscle cells from nine different adult canine macrovessels: the aorta, coronary artery, vena cava, portal vein, femoral artery, femoral vein, saphenous vein, pulmonary vein, and pulmonary artery. We identified both reported and novel expression patterns defining specialized adult blood vessels. Our findings also show that adult vascular cells in culture express a remarkably high number of transcription factors crucial to organ development in the embryo. The persistent expression of these genes in culture indicates that these genes are not regulated by the flow or surrounding cell types but are rather fixed in the molecular memory. Therefore, our findings prompt the re-thinking of the extrapolation of results from single-origin endothelial cell systems.