bluuebunny/crossref_metadata_2025_split huggingface dataset:
Venous Thromboembolism Chemoprophylaxis in Trauma and Emergency General Surgery Patients: A Systematic Review
Authors: Sanchez Carol , Nguyen Jackie , Baroutjian Amanda , Gill Sabrina , McKenney Mark , Elkbuli Adel 
Published: September 2021

Background:
Appropriate venous thromboembolism (VTE) chemoprophylaxis in trauma and emergency general surgery (EGS) patients is crucial.

Objective:
The purpose of this study is to review the recent literature and offer recommendations for VTE chemoprophylaxis in trauma and EGS patients.

Methods:
We conducted a literature search from 2000 to 2021 for articles investigating VTE chemoprophylaxis in adult trauma and EGS patients. This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines.

Results:
Our search resulted in 34 articles. Most studies showed low-molecular-weight heparin (LMWH) is similar to unfractionated heparin (UFH) for VTE prevention; however, LMWH was more commonly used. Adjusted chemoprophylaxis dosing did not change the VTE rate but the timing did. Direct oral anticoagulants (DOACs) have been shown to be safe and effective in trauma and traumatic brain injury (TBI)/spinal cord injury (SCI). Studies showed VTE prophylaxis in EGS can be inconsistent and improves with guidelines that lower VTE events.

Conclusions:
There may be no benefit to receiving LMWH over UFH in trauma patients. In addition, different drugs under the class of LMWH do not change the incidence of VTE. Adjusted dosing of enoxaparin does not seem to affect VTE incidence. The use of DOACs in the trauma TBI and SCI setting has been shown to be safe and effective in reducing VTE. One important consideration with VTE prophylaxis may be the timing of prophylaxis initiation, specifically as it relates to TBI, with a higher likelihood of developing VTE as time progresses. EGS patients are at a high risk of VTE. Improved compliance with clinical guidelines in this population is correlated with decreased thrombotic events.
Mitochondrial DNA: Unraveling the “other” genome
Authors: Heuer Beth 
Published: September 2021

ABSTRACT
The mitochondrial genome, which contains all of the hereditary information within human mitochondria, consists of 16,569 base pairs of double-stranded DNA that encode 37 genes. Pathogenic mutations of mitochondrial DNA (mtDNA) cause dysfunction of the respiratory chain and the process of oxidative phosphorylation (OXPHOS), leading to impaired adenosine triphosphate synthesis. Nuclear DNA (nDNA) mutations can affect structural subunits or assembly factors of one of the five OXPHOS complexes. Mitochondrial diseases are a heterogeneous group of disorders, ranging from mtDNA single-point mutations and large-scale deletions to mitochondrial depletion syndromes, resulting from nDNA pathogenic mutations. Manifestations of mitochondrial disease are multisystemic, and organs with substantial energy requirements are most typically affected. Mitochondrial disorders are progressive in nature, and prognosis is dependent on the organs involved and the rate and severity of disease progression. A multidisciplinary team approach is needed to monitor and manage disease sequelae.
MuSK Myasthenia Gravis Presenting with Bilateral Vocal Cord Abduction Paresis
Authors: Santilli Ashley , Stitt Derek 
Published: September 2021

Introduction:
Approximately 39% to 49% of patients with previously diagnosed acetylcholine receptor antibody-negative myasthenia gravis have been found to be muscle-specific tyrosine kinase (MuSK) antibody positive. These patients have a presentation that typically includes oculobulbar weakness, poorer response to cholinesterase inhibitors, and higher risk for acute clinical decompensation that necessitates plasma exchange. MuSK patients can require more aggressive maintenance immunosuppression earlier-on to maintain stability, often with rituximab.

Case Report:
The authors report the case of a 45-year-old woman who presented with months of worsening hoarseness and exertional dyspnea. Laryngoscopy revealed limited abduction of vocal cords bilaterally as the source of the complaint. Examination revealed ophthalmoparesis and fatigable proximal muscle weakness. She was found to have elevated MuSK antibodies that, along with evidence of neuromuscular junction transmission defect on nerve conduction studies, confirmed the diagnosis of MuSK myasthenia gravis. She experienced no improvement with pyridostigmine and decompensated despite receiving oral steroids, requiring intubation. However, she dramatically improved with plasma exchange and has since been doing well on rituximab therapy.

Conclusion:
Dysphonia with hoarse quality secondary to vocal cord abduction paresis is a rare presentation of myasthenia gravis, as opposed to the typical flaccid dysarthria seen in bulbar myasthenia and should raise suspicion for MuSK antibody positivity. MuSK myasthenia gravis cases can be more refractory to treatment with cholinesterase inhibitors and are more likely to cause exacerbations and myasthenia crisis. Therefore, early and accurate diagnosis with appropriate antibody testing is imperative to avoid delays in treatment to prevent potentially life-threatening outcomes.
The early impact of vaccination against SARS-CoV-2 in Region Stockholm, Sweden
Authors: Isitt Catherine , Sjöholm Daniel , Hergens Maria-Pia , Granath Fredrik , Nauclér Pontus 
Published: September 2021

AbstractVaccination against SARS-CoV-2 started in Region Stockholm, Sweden in December 2020 with those in long-term care facilities or receiving home care vaccinated first followed by those aged over 80 years. In this population-based, retrospective cohort study, we performed a Poisson regression to model the expected incidence of infections and deaths which we compared to the observed incidence and compared this to an unvaccinated control group of those aged 18-79 years. The aim of this study was to measure the early impact of the vaccination programme in Region Stockholm.Infections and deaths reduced substantially amongst the first two groups targeted for SARS-CoV-2 vaccination with an estimated total 3112 infections prevented, and 854 deaths prevented in these two groups from 4 weeks after the introduction of vaccination through to 2nd May 2021.
A Novel Optical Design Enabling Lightweight and Large Field-of-View Head-Mounted Microscopes
Authors: Scherrer J. R. , Lynch Galen F. , Zhang Jie J. , Fee Michale S. 
Published: September 2021

AbstractWe present a novel fluorescence microscope light path that enables imaging, during free behavior, of thousands of neurons in mice and hundreds of neurons in juvenile songbirds. The light path eliminates traditional illumination optics, allowing for head-mounted microscopes that have both a lower weight and a larger field-of-view (FOV) than previously possible. Using this light path, we designed two microscopes: one optimized for field-of-view (∼4 mm FOV; 1.4 g), and the other optimized for weight (1.0 mm FOV; 1.0 g).
Organization and engagement of a prefrontal-olfactory network during olfactory selective attention
Authors: Cansler Hillary L. , in ’t Zandt Estelle E , Carlson Kaitlin S. , Khan Waseh T. , Ma Minghong , Wesson Daniel W. 
Published: September 2021

AbstractSensory perception is profoundly shaped by attention. Attending to an odor strongly regulates if and how a smell is perceived – yet the brain systems involved in this process are unknown. Here we report integration of the medial prefrontal cortex (mPFC), a collection of brain regions integral to attention, with the olfactory system in the context of selective attention to odors. First, we used tracing methods to establish the tubular striatum (TuS, also known as the olfactory tubercle) as the primary olfactory region to receive direct mPFC input in rats. Next, we recorded local field potentials from the olfactory bulb (OB), mPFC, and TuS while rats completed an olfactory selective attention task. Gamma power and coupling of gamma oscillations with theta phase were consistently high as rats flexibly switched their attention to odors. Beta and theta synchrony between mPFC and olfactory regions were elevated as rats switched their attention to odors. Finally, we found that sniffing was consistent despite shifting attentional demands, suggesting that the mPFC-OB theta coherence is independent of changes in active sampling. Together, these findings begin to define an olfactory attention network wherein mPFC activity, as well as that within olfactory regions, are coordinated in manners based upon attentional states.
The Sec61 translocon is a therapeutic vulnerability in Multiple Myeloma
Authors: Domenger Antoine , Choisy Caroline , Baron Ludivine , Mayau Véronique , Deriano Ludovic , Arnulf Bertrand , Bories Jean-Christophe , Dadaglio Gilles , Demangel Caroline 
Published: September 2021

AbstractMultiple Myeloma (MM) is an incurable malignancy characterized by the uncontrolled expansion of plasma cells in the bone marrow. While proteasome inhibitors like bortezomib efficiently halt MM progression, drug resistance or toxicity inevitably develop. Here, we used a recently discovered inhibitor, mycolactone, to assess the interest of targeting the Sec61 translocon in MM. In human cell lines and tumors from MM patients, mycolactone triggered pro-apoptotic endoplasmic reticulum stress responses synergizing with bortezomib for induction of MM cell death, irrespective of their resistance to proteasome inhibition. Notably, this synergy was selective of cancer cells and extended to B cell acute lymphoblastic leukemia. Sec61 blockade also caused collateral defects in MM secretion of immunoglobulins and expression of pro-survival interleukin (IL)-6 receptor and CD40, whose activation stimulates IL-6 production. Further, the mycolactone-bortezomib combination demonstrated superior therapeutic efficacy over single drug treatments in immunodeficient mice engrafted with MM cells, without inducing toxic side effects. Collectively, these findings establish Sec61 blockers as novel anti-MM agents and reveal the interest of targeting both the translocon and the proteasome in proteostasis-addicted tumors.
Vulnerability to cavitation is linked to home climate precipitation across eight eucalypt species
Authors: Coleman David , Merchant Andrew , Salter William T. 
Published: September 2021

AbstractVulnerability to cavitation in leaves is the result of highly adaptive anatomical and physiological traits that can be linked to water availability in a species’ climate of origin. Despite similar gross leaf morphology, eucalypt species are often confined to specific climate envelopes across the variable rainfall environments of Australia. In this study, we investigate how the progression of cavitation differs among eucalypts and whether this is related to other hydraulic and physical leaf traits. We used the Optical Visualisation technique to capture cavitation progression across the leaves of eight eucalypt species (Angophora crassifolia, Corymbia tessellaris, Eucalyptus atrata, Eucalyptus grandis, Eucalyptus laevopinea, Eucalyptus longifolia, Eucalyptus macrandra, Eucalyptus tereticornis) from a wide range of climates and grown in a common garden setting. Vulnerability to cavitation, represented by the leaf water potential required for 50% cavitation of leaf vessels, varied significantly among species (−3.48 MPa to −8.25 MPa) and correlated linearly with home climate precipitation and leaf SLA (R2of 0.64 and 0.75, respectively). P12-P88, the range of water potentials between which 12% to 88% of cavitation occurs, was decoupled from P50 but also correlated with leaf SLA (R2of 0.72). We suggest the magnitude of P12-P88 may be representative of a species’ drought strategy – a large P12-P88 signifying leaves that exhibit drought tolerance (retention of leaves under drought conditions) and a small P12-P88 signifying drought avoidance (leaf shedding after a threshold of drought is reached). Our results agree with other studies that highlight these cavitation metrics as genetically fixed traits. Turgor loss point, on the other hand, may be more plastic, as evidenced by the low variability of this trait across these eucalypt species grown in a common garden environment. Further study will help to establish the SLA-related anatomical traits that impart cavitation resistance and to extend these conclusions to a greater number of species and home climates.
Reduced H+channel activity disrupts pH homeostasis and calcification in coccolithophores at low ocean pH
Authors: Kottmeier Dorothee , Chrachri Abdul , Langer Gerald , Helliwell Katherine , Wheeler Glen L. , Brownlee Colin 
Published: September 2021

AbstractCoccolithophores produce the bulk of ocean biogenic calcium carbonate but this process is predicted to be negatively affected by future ocean acidification scenarios. Since coccolithophores calcify intracellularly, the mechanisms through which changes in seawater carbonate chemistry affect calcification remain unclear. Here we show that voltage-gated H+channels in the plasma membrane ofCoccolithus braarudiiserve to regulate pH and maintain calcification under normal conditions, but have greatly reduced activity in cells acclimated to low pH. This disrupts intracellular pH homeostasis and impairs the ability ofC. braarudiito remove H+generated by the calcification process, leading to specific coccolith malformations. These coccolith malformations can be reproduced by pharmacological inhibition of H+channels. Heavily-calcified coccolithophore species such asC. braarudii, which make the major contribution to carbonate export to the deep ocean, have a large intracellular H+load and are likely to be most vulnerable to future decreases in ocean pH.
Ineffective neutralization of the SARS-CoV-2 Mu variant by convalescent and vaccine sera
Authors: Uriu Keiya , Kimura Izumi , Shirakawa Kotaro , Takaori-Kondo Akifumi , Nakada Taka-aki , Kaneda Atsushi ,   The Genotype to Phenotype Japan (G2P-Japan) Consortium, Nakagawa So , Sato Kei 
Published: September 2021

AbstractOn August 30, 2021, the WHO classified the SARS-CoV-2 Mu variant (B.1.621 lineage) as a new variant of interest. The WHO defines “comparative assessment of virus characteristics and public health risks” as primary action in response to the emergence of new SARS-CoV-2 variants. Here, we demonstrate that the Mu variant is highly resistant to sera from COVID-19 convalescents and BNT162b2-vaccinated individuals. Direct comparison of different SARS-CoV-2 spike proteins revealed that Mu spike is more resistant to serum-mediated neutralization than all other currently recognized variants of interest (VOI) and concern (VOC). This includes the Beta variant (B.1.351) that has been suggested to represent the most resistant variant to convalescent and vaccinated sera to date (e.g., Collier et al, Nature, 2021; Wang et al, Nature, 2021). Since breakthrough infection by newly emerging variants is a major concern during the current COVID-19 pandemic (Bergwerk et al., NEJM, 2021), we believe that our findings are of significant public health interest. Our results will help to better assess the risk posed by the Mu variant for vaccinated, previously infected and naïve populations.
Structure and dynamics of Toll immunoreceptor activation in the mosquito Aedes aegypti
Authors: Saucereau Yoann , Wilson Tom H. , Tang Matthew C. K. , Moncrieffe Martin C. , Hardwick Steven W. , Chirgadze Dimitri Y. , Soares Sandro G. , Marcaida Maria Jose , Gay Nick , Gangloff Monique 
Published: September 2021

ABSTRACTAedes aegypti has evolved to become an efficient vector for arboviruses but the mechanisms of host-pathogen tolerance are unknown. Immunoreceptor Toll and its ligand Spaetzle have undergone duplication which may allow neofunctionalization and adaptation. Here we present cryo-EM structures and biophysical characterisation of low affinity Toll5A complexes that display transient but specific interactions with Spaetzle1C, forming asymmetric complexes, with only one ligand clearly resolved. Loop structures of Spaetzle1C and Toll5A intercalate, temporarily bridging the receptor C-termini to promote signalling. By contrast unbound receptors form head-to-head homodimers that keep the juxtamembrane regions far apart in an inactive conformation. Interestingly the transcriptional signature of Spaetzle1C differs from other Spaetzle cytokines and controls genes involved in innate immunity, metabolism and tissue regeneration. Taken together our results explain how upregulation of Spaetzle1C in the midgut and Toll5A in the salivary gland shape the concomitant immune response.
Two engineered AAV capsid variants for efficient transduction of human cortical neurons directly converted from iPSC
Authors: Fischer Sandra , Weinmann Jonas , Gillardon Frank 
Published: September 2021

AbstractRecombinant adeno-associated virus (AAV) is the most widely used vector for gene therapy in clinical trials. To increase transduction efficiency and specificity, novel engineered AAV variants with modified capsid sequences are evaluated in human cell cultures and non-human primates. In the present study, we tested two novel AAV capsid variants, AAV2-NNPTPSR and AAV9-NVVRSSS, in human cortical neurons, which were directly converted from human induced pluripotent stem cells and cocultured with rat primary astrocytes. AAV2-NNPTPSR variant efficiently transduced both induced human cortical glutamatergic neurons and induced human cortical GABAergic interneurons. By contrast, AAV9-NVVRSSS variant transduced both induced human cortical neurons and cocultured rat primary astrocytes. High viral titers (1×10E5 viral genomes per cell) caused a significant decrease in viability of induced human cortical neurons. Low viral titers (1×10E4 viral genomes per cell) lead to a significant increase in the neuronal activity marker c-Fos in transduced human neurons following treatment with a potassium channel blocker, which may indicate functional alterations induced by viral transduction and/or transgene expression.
In vivocharacterization and application of a novel potassium channel-based optogenetic silencer in the healthy and epileptic mouse hippocampus
Authors: Kleis P , Paschen E , Häussler U , Bernal Sierra YA , Haas CA 
Published: September 2021

AbstractThe performance of available optogenetic inhibitors remains insufficient due to low light sensitivity, short-lasting photocurrents, and unintended changes in ion distributions. To overcome these limitations, a novel potassium channel-based optogenetic silencer was developed and successfully applied in variousin vitroand acutein vivosettings (Bernal Sierra et al., 2018). This tool, a two-component construct called PACK, comprises a photoactivated adenylyl cyclase (bPAC) and a cAMP-dependent potassium channel (SthK). Here, we examined the long-term inhibitory action and side effects of the PACK construct in healthy and epileptic adult male mice. We targeted hippocampal CA1 pyramidal cells using a viral vector and enabled illumination of these neurons via an implanted optic fiber. Local field potential (LFP) recordings from the CA1 of freely moving mice revealed significantly reduced neuronal activity during 50-minute intermittent illumination, especially in the beta and gamma frequency ranges. Adversely, PACK expression in healthy mice induced chronic astrogliosis, dispersion of pyramidal cells, and generalized seizures. These side effects were independent of the light application and were also present in mice expressing bPAC without the potassium channel. Additionally, light-activation of bPAC alone increased neuronal activity, presumably via enhanced cAMP signaling. In chronically epileptic mice, the dark activity of bPAC/PACK in CA1 prevented the spread of spontaneous epileptiform activity from the seizure focus to the contralateral bPAC/PACK-expressing hippocampus. Taken together, the PACK tool is a potent optogenetic inhibitor but requires refinement of its light-sensitive domain to avoid unexpected physiological changes.Significance statementOptogenetics allows precise manipulation of neuronal activity via genetically encoded light-sensitive proteins. Unfortunately, available optogenetic inhibitors are not suitable for prolonged use. The newly developed two-component potassium channel-based optogenetic inhibitor, PACK, has been identified as a potent silencer of neurons in various acute experiments. Here, we characterized the PACK construct in freely behaving healthy and epileptic mice. We targeted the PACK silencer specifically to CA1 pyramidal neurons, where illumination with short light pulses at low frequencies reliably reduced neuronal activity. In chronically epileptic mice, PACK prevented the spread of epileptiform activity from the seizure focus to the contralateral PACK-expressing hippocampus. The major disadvantage of the PACK silencer is its light-sensitive domain, the bPAC adenylyl cyclase, which may induce side effects.
Genetic epidemiology of blood type, disease and trait variants, and genome-wide genetic diversity in over 11,000 domestic cats
Authors: Anderson Heidi , Davison Stephen , Lytle Katherine M. , Honkanen Leena , Freyer Jamie , Mathlin Julia , Kyöstilä Kaisa , Inman Laura , Louviere Annette , Foran Rebecca Chodroff , Forman Oliver P. , Lohi Hannes , Donner Jonas 
Published: September 2021

AbstractIn the largest DNA-based study of domestic cat to date, 11,036 individuals (10,419 pedigreed cats from 91 breeds and breed types and 617 non-pedigreed cats) were genotyped via commercial panel testing, elucidating the distribution and frequency of known genetic variants associated with blood type, disease and physical traits across cat breeds. Blood group determining variants, which are relevant clinically and in cat breeding, were genotyped to assess the across breed distribution of blood types A, B and AB. Extensive panel testing identified 13 disease-associated variants in 48 breeds or breed types for which the variant had not previously been observed, strengthening the argument for panel testing across populations. The study also indicates that multiple breed clubs have effectively used DNA testing to reduce disease-associated genetic variants within certain pedigreed cat populations. Appearance-associated genetic variation in all cats is also discussed. Additionally, we combined genotypic data with phenotype information and clinical documentation, actively conducted owner and veterinarian interviews, and recruited cats for clinical examination to investigate the causality of a number of tested variants across different breed backgrounds. Lastly, genome-wide informative SNP heterozygosity levels were calculated to obtain a comparable measure of the genetic diversity in different cat breeds.This study represents the first comprehensive exploration of informative Mendelian variants in felines by screening over 10,000 domestic cats. The results qualitatively contribute to the understanding of feline variant heritage and genetic diversity and demonstrate the clinical utility and importance of such information in supporting breeding programs and the research community. The work also highlights the crucial commitment of pedigreed cat breeders and registries in supporting the establishment of large genomic databases that when combined with phenotype information can advance scientific understanding and provide insights that can be applied to improve the health and welfare of cats.