bluuebunny/crossref_metadata_2025_split huggingface dataset:
Certainties fading away: β-blockers do not worsen chronic obstructive pulmonary disease
Authors: Verdecchia Paolo , Cavallini Claudio , Coiro Stefano , Riccini Clara , Angeli Fabio 
Published: October 2021

Abstract
For many years, β-blockers have been considered contraindicated in patients with heart failure (HF) and in those with bronchial asthma or even chronic obstructive pulmonary disease (COPD) although without clear evidence of asthma. Today, despite overwhelming evidence of the usefulness of β-blockers, especially in HF with reduced left ventricular ejection fraction (HFrEF), and in ischaemic heart disease, some reluctance persists in using these drugs when COPD coexists. Such resistance is due to the fear that a possible worsening of bronchospasm induced by β-blockers could induce negative effects greater than the benefits. The Guidelines of the European Society of Cardiology clearly suggest that: (i) implantation of a cardiac defibrillator (ICD) are not contraindicated in COPD without clear evidence of bronchial asthma; (ii) β-blockers are only ‘relatively’ contraindicated when there is certainty of bronchial asthma with a documented bronchodilator response to the β2 stimulant. Therefore, bronchial asthma is not an absolute contraindication to β-blockers. The cardiologist should not limit the diagnosis of COPD to clinical suspicion, but should rely on a spirometry examination associated with any bronchodilation tests. In any case, selective β1 blockers are preferred, starting at a basic dose, which ensure a better dilator response to bronchodilators and in any case cause less bronchospasm than non-selective β-blockers. Unfortunately, there is still some reluctance to the use of β-blockers in patients with COPD associated with HF, which should be eliminated.
The ‘dreaded PFO’: anatomical and functional features of high risk for stroke
Authors: Radico Francesco , Foglietta Melissa , Di Fulvio Maria , Appignani Marianna , Rossi Serena , Angelis Maria Vittoria De , Gallina Sabina , Zimarino Marco 
Published: October 2021

AbstractPatent foramen ovale (PFO) has a high prevalence in general population and can be implicated in cryptogenic stroke among young people. Recent trials have shown that transcatheter PFO closure is superior to medical treatment in the secondary prevention of ischaemic stroke. The benefit in the reduction of stroke recurrence is particularly evident in patients who have documentation of a PFO with high-risk characteristics. Therefore, after the assessment of a clear causal relationship with the event, a thoughtful documentation of anatomic (height, length, presence of an aneurysmatic or a floppy atrial septum, a prominent Eustachian valve or Chiari’s network, an acute angle with the inferior vena cava) and functional high-risk characteristics is mandatory.
Nitric Oxide Signals Through IRAG to Inhibit TRPM4 Channels and Dilate Cerebral Arteries
Authors: Ali Sher , Solano Alfredo Sanchez , Gonzales Albert L , Thakore Pratish , Krishnan Vivek , Yamasaki Evan , Earley Scott 
Published: October 2021

Abstract

Nitric oxide (NO) relaxes vascular smooth muscle cells (SMCs) and dilates blood vessels by increasing intracellular levels of cyclic guanosine monophosphate (cGMP), which stimulates the activity of cGMP-dependent protein kinase (PKG). However, the vasodilator mechanisms downstream of PKG remain incompletely understood. Here, we found that transient receptor potential melastatin 4 (TRPM4) cation channels, which are activated by Ca2+ released from the sarcoplasmic reticulum (SR) through inositol triphosphate receptors (IP3Rs) under native conditions, are essential for SMC membrane depolarization and vasoconstriction. We hypothesized that signaling via the NO/cGMP/PKG pathway causes vasodilation by inhibiting TRPM4. We found that TRPM4 currents activated by stretching the plasma membrane or directly activating IP3Rs were suppressed by exogenous NO or a membrane-permeable cGMP analog, the latter of which also impaired IP3R-mediated release of Ca2+ from the SR. The effects of NO on TRPM4 activity were blocked by inhibition of soluble guanylyl cyclase or PKG. Notably, upon phosphorylation by PKG, IRAG (IP3R-associated PKG substrate) inhibited IP3R-mediated Ca2+ release, and knockdown of IRAG expression diminished NO-mediated inhibition of TRPM4 activity and vasodilation. Using superresolution microscopy, we found that IRAG, PKG, and IP3Rs form a nanoscale signaling complex on the SR of SMCs. We conclude that NO/cGMP/PKG signaling through IRAG inhibits IP3R-dependent activation of TRPM4 channels in SMCs to dilate arteries.

Significance Statement
Nitric oxide is a gaseous vasodilator produced by endothelial cells that is essential for cardiovascular function. Although NO-mediated signaling pathways have been intensively studied, the mechanisms by which they relax SMCs to dilate blood vessels remain incompletely understood. In this study, we show that NO causes vasodilation by inhibiting the activity of Ca2+-dependent TRPM4 cation channels. Probing further, we found that NO does not act directly on TRPM4 but instead initiates a signaling cascade that inhibits its activation by blocking the release of Ca2+ from the SR. Thus, our findings reveal the essential molecular pathways of NO-induced vasodilation—a fundamental unresolved concept in cardiovascular physiology.
Translational control of lipogenesis links protein synthesis and phosphoinositide signaling with nuclear division inSaccharomyces cerevisiae
Authors: Maitra Nairita , Hammer Staci , Kjerfve Clara , Bankaitis Vytas A , Polymenis Michael 
Published: October 2021

AbstractContinuously dividing cells coordinate their growth and division. How fast cells grow in mass determines how fast they will multiply. Yet, there are few, if any, examples of a metabolic pathway that actively drives a cell cycle event instead of just being required for it. Here, we show that translational upregulation of lipogenic enzymes in Saccharomyces cerevisiae increased the abundance of lipids and promoted nuclear elongation and division. Derepressing translation of acetyl-CoA carboxylase and fatty acid synthase also suppressed cell cycle-related phenotypes, including delayed nuclear division, associated with Sec14p phosphatidylinositol transfer protein deficiencies, and the irregular nuclear morphologies of mutants defective in phosphatidylinositol 4-OH kinase activities. Our results show that increased lipogenesis drives a critical cell cycle landmark and report a phosphoinositide signaling axis in control of nuclear division. The broad conservation of these lipid metabolic and signaling pathways raises the possibility these activities similarly govern nuclear division in other eukaryotes.
Differential effects of two catalytic mutations on full-length PRDM9 and its isolated PR/SET domain reveal a case of pseudomodularity
Authors: Powers Natalie R. , Billings Timothy , Paigen Kenneth , Petkov Petko M. 
Published: October 2021

Abstract
PRDM9 is a DNA-binding histone methyltransferase that designates and activates recombination hotspots in mammals by locally trimethylating lysines 4 and 36 of histone H3. In mice, we recently reported two independently produced point mutations at the same residue, Glu360Pro (Prdm9EP) and Glu360Lys (Prdm9EK), which severely reduce its H3K4 and H3K36 methyltransferase activities in vivo. Prdm9EP is slightly less hypomorphic than Prdm9EK, but both mutations reduce both the number and amplitude of PRDM9-dependent H3K4me3 and H3K36me3 peaks in spermatocytes. While both mutations cause infertility with complete meiotic arrest in males, Prdm9EP, but not Prdm9EK, is compatible with some female fertility. When we tested the effects of these mutations in vitro, both Prdm9EP and Prdm9EK abolished H3K4 and H3K36 methyltransferase activity in full-length PRDM9. However, in the isolated PRDM9 PR/SET domain, these mutations selectively compromised H3K36 methyltransferase activity, while leaving H3K4 methyltransferase activity intact. The difference in these effects on the PR/SET domain vs the full-length protein shows that PRDM9 is not an intrinsically modular enzyme; its catalytic domain is influenced by its tertiary structure and possibly by its interactions with DNA and other proteins in vivo. These two informative mutations illuminate the enzymatic chemistry of PRDM9, and potentially of PR/SET domains in general, reveal the minimal threshold of PRDM9-dependent catalytic activity for female fertility, and potentially have some practical utility for genetic mapping and genomics.
Establishment of a Reliable Model to Study the Failure of Fracture Healing in Aged Mice
Authors: Menger Maximilian M , Laschke Matthias W , Scheuer Claudia , Bauer David , Bleimehl Michelle , Später Thomas , Rollmann Mika F , Braun Benedikt J , Herath Steven C , Raza Ahsan , Menger Michael D , Histing Tina 
Published: October 2021

Abstract
The failure of fracture healing represents a substantial clinical problem. Moreover, aged patients demonstrate an elevated risk for failed bone healing. However, murine models to study the failure of fracture healing are established only in young adult animals. Therefore, the aim of this study was to develop a reliable model to study failed fracture healing in aged mice. After creation of a 1.8-mm segmental defect and periosteal resection, femora of aged mice (18–20 months) and young adult control mice (3–4 months) were stabilized by pin-clip fixation. Segmental defects were analyzed by means of biomechanics, x-ray, and micro-computed tomography, as well as histomorphometric, immunohistochemical, and Western blot analysis. After 10 weeks, all animals showed a complete lack of osseous bridging, resulting in fracture healing failure. Segmental defects in aged mice revealed a reduced bone formation and vascularization when compared to young adult mice. This was associated with a decreased expression of bone formation markers. In addition, we detected a reduced number of tartrate-resistant acid phosphatase-positive osteoclasts and an elevated osteoprotegerin/receptor activator of NF-ĸB ligand ratio in aged animals, indicating a reduced osteoclast activity. Moreover, aged animals showed also an enhanced inflammatory response, characterized by an increased infiltration of macrophages within the callus tissue. Taken together, we herein report for the first time a reliable model to study fracture healing failure in aged mice. In the future, the use of this model enables us to study novel therapeutic strategies and molecular mechanics of failed fracture healing during aging.
“We Closed the Ports to Protect Refugees.” Hygienic Borders and Deterrence Humanitarianism during Covid-19
Authors: Tazzioli Martina , Stierl Maurice 
Published: October 2021

Abstract
This article investigates how the security-humanitarian rationale that underpins migration governmentality has been restructured by and inflected in light of hygienic-sanitary borders which enforce racialised confinement in the name of both migrants' and citizens' safety from infection by Covid-19. Focusing on the politics of migration containment along EUrope's frontiers, examining in particular border reinforcements carried out by Italy, Malta and Greece, we interrogate how the pandemic has been exploited to enact deterrence through hygienic-sanitary border enforcements. These enforcements are underpinned by an ambivalent security-humanitarian narrative that crafts migrants as subjects who cannot be protected by EU member states from the pandemic if allowed inside, and, at once, as potential vehicles of contagion - ‘Corona spreaders’ - and thus as dangers on a bacterial-hygienic level. Our article demonstrates that these EUropean border measures are more than temporary responses to an unprecedented health crisis. Rather, the pandemic has been seized as an opportunity to strengthen existing deterrence measures and hamper migrants' access to asylum through biopolitical and spatial tactics that aim to restructure the border regime. While emphasising the historical trajectories and continuities underwriting these current developments, we contend that the pandemic functions as an accelerator of dynamics of migrant incarceration and containment.
Player Engagement with Games: Formal Reliefs and Representation Checks
Authors: Egerton Karl 
Published: October 2021

Abstract
Alongside the direct parallels and contrasts between traditional narrative fiction and games, there lie certain partial analogies that provide their own insights. This article begins by examining a direct parallel between narrative fiction and games—the role of fictional reliefs and reality checks in shaping aesthetic engagement—before arguing that from this a partial analogy can be developed stemming from a feature that distinguishes most games from most traditional fictions: the presence of rules. The relation between rules and fiction in games has heretofore been acknowledged but not examined in detail, giving an impression of a tension that is constant. However, the paired concepts of formal reliefs and representation checks, once introduced, allow us to explain how rules and fiction interact to alter the ways in which players engage with games in a dynamic but limited way.
Sepsis prediction, early detection, and identification using clinical text for machine learning: a systematic review
Authors: Yan Melissa Y , Gustad Lise Tuset , Nytrø Øystein 
Published: October 2021

Abstract

Objective
To determine the effects of using unstructured clinical text in machine learning (ML) for prediction, early detection, and identification of sepsis.

Materials and methods
PubMed, Scopus, ACM DL, dblp, and IEEE Xplore databases were searched. Articles utilizing clinical text for ML or natural language processing (NLP) to detect, identify, recognize, diagnose, or predict the onset, development, progress, or prognosis of systemic inflammatory response syndrome, sepsis, severe sepsis, or septic shock were included. Sepsis definition, dataset, types of data, ML models, NLP techniques, and evaluation metrics were extracted.

Results
The clinical text used in models include narrative notes written by nurses, physicians, and specialists in varying situations. This is often combined with common structured data such as demographics, vital signs, laboratory data, and medications. Area under the receiver operating characteristic curve (AUC) comparison of ML methods showed that utilizing both text and structured data predicts sepsis earlier and more accurately than structured data alone. No meta-analysis was performed because of incomparable measurements among the 9 included studies.

Discussion
Studies focused on sepsis identification or early detection before onset; no studies used patient histories beyond the current episode of care to predict sepsis. Sepsis definition affects reporting methods, outcomes, and results. Many methods rely on continuous vital sign measurements in intensive care, making them not easily transferable to general ward units.

Conclusions
Approaches were heterogeneous, but studies showed that utilizing both unstructured text and structured data in ML can improve identification and early detection of sepsis.
The significance of female dimorphic characters of primary freshwater crabs for the systematics of Eubrachyura (Crustacea: Decapoda: Brachyura)
Authors: Cumberlidge Neil , Johnson Emily C , Leever Ellen M , Soma Julia B , Ahles Kaitlyn M , Kamanli Seyit A , Clark Paul F 
Published: October 2021

AbstractMale pleopods, pleon, and gonopods 1 and 2 of primary brachyuran freshwater crabs have been used for well over 100 years as important taxonomic characters to distinguish between species, genera, and families. In contrast, while there have been a number of studies of female dimorphic brachyuran characters, including two families of primary freshwater crabs, their pleopods have been virtually ignored and presumed to be uninformative with respect to systematics. Consequently, we provide for the first-time descriptions and images of the female pleon, pleopods, egg attachment sites, and telson of representatives of five primary freshwater crab families: Potamidae, Potamonautidae, Gecarcinucidae, Pseudothelphusidae, and Trichodactylidae. For preliminary comparative purposes, similar details are also presented for species representing two Heterotremata families, e.g., Epialtidae and Portunidae, and four Thoracotremata families e.g., Gecarcinidae, Grapsidae, Sesarmidae, and Varunidae. This morphological comparative study of female characters provides a new dataset for family-level comparisons of freshwater crabs. As a result, two groups of primary freshwater crabs are recognized: a revised Potamoidea Ortmann, 1896 for Potamidae, Potamonautidae, Deckeniidae, Gecarcinucidae, Pseudothelphusidae, and Epiloboceridae, and Trichodactyloidea comprising Trichodactylidae. Although all of the non-trichodactylid freshwater crab families are morphological heterotremes with male coxal gonopores and female sternal gonopores, their current Heterotremata assignment is here being questioned. From new evidence presented here, this group of primary freshwater Brachyura may be more properly positioned outside of Heterotremata, as a sister group of Thoracotremata. This use of novel female diagnostic characters, however, supports the continued assignment of Trichodactylidae to Heterotremata.
Alternative Chemical Control Options and Monitoring Techniques for Triops longicaudatus (Notostraca: Triopsidae) in California Rice
Authors: Bloese Joanna B , Goding Kevin M , Godfrey Larry D 
Published: October 2021

Abstract
The tadpole shrimp (Triops longicaudatus (Leconte); Notostraca; Triopsidae) is a vernal pool crustacean that has emerged as a significant pest for many rice farmers in California. Currently, lambda-cyhalothrin is the commercial standard and sole management practice for TPS, but resistance appears to be emerging. Field and laboratory trials were conducted from 2015 to 2018 at the Rice Experiment Station in Biggs, California, and in greenhouses at the University of California (UC) Davis to evaluate the efficacy of several alternative chemical controls and to explore early indicators of TPS activity and damage as monitoring tools. TPS mortality in plots treated with azadirachtin was not significantly different from those in the untreated control across all trials. Copper sulfate, lambda-cyhalothrin, and clothianidin were consistently effective across both lab and field trials. Chlorantraniliprole generated effective control in four of the five trials, whereas two diflubenzuron rates generated adequate control in the field, but not in laboratory bioassays. Thus, there appear to be several effective alternative control options available for farmers, should resistance to lambda-cyhalothrin continue to spread. Water turbidity (measured using a scale of 1–4) and the number of dislodged seedlings were both significantly correlated with TPS counts in field studies. Turbidity exhibited the highest correlations with TPS counts, suggesting that with further refinement it could play a valuable role in monitoring TPS populations.
Reducing Burnout and Resignations among Frontline Workers: A Field Experiment
Authors: Linos Elizabeth , Ruffini Krista , Wilcoxen Stephanie 
Published: October 2021

AbstractGovernment agencies around the world struggle to retain frontline workers, as high job demands and low job resources contribute to persistently high rates of employee burnout. Although four decades of research have documented the predictors and potential costs of frontline worker burnout, we have limited causal evidence on strategies that reduce it. In this article, we report on a multicity field experiment (n = 536) aimed at increasing perceived social support and affirming belonging among 911 dispatchers. We find that a 6-week intervention that prompts dispatchers to share advice anonymously and asynchronously with their peers in other cities reduces burnout by 8 points (0.4 standard deviations) and cuts resignations by more than half (3.4 percentage points) 4 months after the intervention ended. We provide supporting evidence that the intervention operates by increasing perceived social support and belonging in an online laboratory experiment (n = 497). These findings suggest that low-cost belonging affirmation techniques can reduce frontline worker burnout and help agencies retain workers, saving a mid-sized city at least $400,000 in personnel costs.
Delayed-Onset Neuropathological Complications From a Foramen Magnum and Occipital Crest Focused Traumatic Brain Injury of the Vietnam War and Other Conflicts: Part I, Case Report
Authors: Burkle Frederick M , Hadley Kevin S , Ridge Leah L , Herman Jan K , Kobeissy Firas H 
Published: October 2021

ABSTRACT

Introduction
The diagnosis of traumatic brain injuries is typically based on hemispheric blasts resulting in degrees of unconsciousness and associated cerebral injuries. This case report describes a Vietnam War era setting in which a traumatic blast wave struck the posterior cranium in the region of the foramen magnum, occipital crest, and other skull openings (orbit, oronasal, and ear) and the unique secondary clinical signs and symptoms experienced over time.

Materials and Methods
This case report describes secondary delayed-onset clinical signs and symptoms consistent with progressive decades-long physical and functional complications. The traumatic blast resulted in brief unconsciousness, decreased vision in left eye, confusion, right sided hemotympanum, deafness, severe tinnitus, severe nasopharynx pain and difficulty swallowing, pain in right posterior and occipital area of the head, and loss of dental amalgams. Subsequent exams revealed progressive hyperacusis, sea sickness, dysdiadochokinesis, diagnosis of 9th and 10th cranial nerve traumatic schwannomas, hyperdense changes to the frontal lobe white matter, progressive tinnitus, chronic vertigo, right-sided high-frequency hearing loss, progressive oculo-gyric crisis of Tumarkin-like seizures, left-sided chronic vitreous hemorrhage, and diminished right hemisphere performance of the brain based on neurophysiological assessment. No post-traumatic stress, depression, or other emotional or psychiatric difficulties were claimed.

Conclusion
This case report, unique to the English language scientific literature, discusses in detail the secondary signs and symptoms of a foramen magnum and occipital crest focused-associated blast injury.