bluuebunny/crossref_metadata_2025_split huggingface dataset:
Timing of tracheostomy in acute traumatic spinal cord injury: A systematic review and meta-analysis
Authors: Foran Sarah J. , Taran Shaurya , Singh JM , Kutsogiannis Demetrios James , McCredie Victoria 
Published: September 2021

BACKGROUND
Patients with acute traumatic cervical or high thoracic level spinal cord injury (SCI) typically require mechanical ventilation (MV) during their acute admission. Placement of a tracheostomy is preferred when prolonged weaning from MV is anticipated. However, the optimal timing of tracheostomy placement in patients with acute traumatic SCI remains uncertain. We systematically reviewed the literature to determine the effects of early versus late tracheostomy or prolonged intubation in patients with acute traumatic SCI on important clinical outcomes.

METHODS
Six databases were searched from their inception to January 2020. Conference abstracts from relevant proceedings and the gray literature were searched to identify additional studies. Data were obtained by two independent reviewers to ensure accuracy and completeness. The quality of observational studies was evaluated using the Newcastle Ottawa Scale.

RESULTS
Seventeen studies (2,804 patients) met selection criteria, 14 of which were published after 2009. Meta-analysis showed that early tracheostomy was not associated with decreased short-term mortality (risk ratio [RR], 0.84; 95% confidence interval [CI], 0.39–1.79; p = 0.65; n = 2,072), but was associated with a reduction in MV duration (mean difference [MD], 13.1 days; 95% CI, –6.70 to –21.11; p = 0.0002; n = 855), intensive care unit length of stay (MD, –10.20 days; 95% CI, –4.66 to –15.74; p = 0.0003; n = 855), and hospital length of stay (MD, –7.39 days; 95% CI, –3.74 to –11.03; p < 0.0001; n = 423). Early tracheostomy was also associated with a decreased incidence of ventilator-associated pneumonia and tracheostomy-related complications (RR, 0.86; 95% CI, 0.75–0.98; p = 0.02; n = 2,043 and RR, 0.64; 95% CI, 0.48–0.84; p = 0.001; n = 812 respectively). The majority of studies ranked as good methodologic quality on the Newcastle Ottawa Scale.

CONCLUSION
Early tracheostomy in patients with acute traumatic SCI may reduce duration of mechanical entilation, length of intensive care unit stay, and length of hospital stay. Current studies highlight the lack of high-level evidence to guide the optimal timing of tracheostomy in acute traumatic SCI. Future research should seek to understand whether early tracheostomy improves patient comfort, decreases duration of sedation, and improves long-term outcomes.

LEVEL OF EVIDENCE
Systematic Review, level III.
The impact of emerging Plasmodium knowlesi on accurate diagnosis by light microscopy: a systematic review and modelling analysis
Authors: Huber John H. , Elliott Margaret , Koepfli Cristian , Perkins T. Alex 
Published: September 2021

ABSTRACTThe five Plasmodium spp. that cause human malaria appear similar under light microscopy, which raises the possibility that misdiagnosis could routinely occur in clinical settings. Assessing the extent of misdiagnosis is of particular importance for monitoring P. knowlesi, which co-circulates with the other Plasmodium spp. We performed a systematic review and meta-analysis of studies comparing the performance of microscopy and PCR for diagnosing malaria in settings with co-circulation of the five Plasmodium spp. We assessed the extent to which co-circulation of Plasmodium parasites affects diagnostic outcomes. We fit a Bayesian hierarchical latent class model to estimate variation in microscopy sensitivity and specificity. Mean sensitivity of microscopy was low, yet highly variable across Plasmodium spp., ranging from 41.7% (95% CI: 22.8 – 64.1%) for P. falciparum and 40.3% (22.0 – 61.5%) for P. vivax to 0.119% (0.0121 – 0.640%) for P. knowlesi, 7.57% (2.66 – 22.0%) for P. malariae, and 0.180% (0.00491 – 1.21%) for P. ovale. Observed PCR prevalence was positively correlated with estimated microscopic sensitivity and negatively correlated with estimated microscopic specificity, though the strength of the associations varied by species. Our analysis suggests that co-circulation of Plasmodium spp. undermines the accuracy of microscopy. Sensitivity was considerably lower for P. knowlesi, P. malariae, and P. ovale. The negative association between specificity and prevalence imply that less frequently encountered species may be misdiagnosed as more frequently encountered species. Together, these results suggest that the burden of P. knowlesi, P. malariae, and P. ovale may be underappreciated in a clinical setting.
Anticipating racial/ethnic mortality displacement from COVID-19
Authors: Kissler Stephen M. , Grad Yonatan H. 
Published: September 2021

AbstractIn 2020, life expectancy in the United States decreased by an estimated 1.5 years. Due to mortality displacement during the COVID-19 pandemic, life expectancy could soon rebound to above its pre-pandemic baseline. We estimated the size and duration of this anticipated rise in life expectancy through 2030. We found that this rebound could persist for years and will likely be most pronounced in minority populations who suffered the highest rates of mortality during the pandemic. Accounting for this artificial rebound will be critical to avoid funneling resources away from populations that still urgently need them.
Strong experimental support for the hologenome hypothesis revealed from Drosophila melanogaster selection lines
Authors: Kristensen Torsten Nygaard , Schönherz Anna A. , Rohde Palle Duun , Sørensen Jesper Givskov , Loeschcke Volker 
Published: September 2021

AbstractRecently it has been proposed, that the holobiont, i.e., the host and its associated microbiome, constitute a distinct biological entity, on which selection operates. This is a fascinating idea that so far has limited empirical justification. Here Drosophila melanogaster lines from a large-scale artificial selection experiment, where we selected for stress resistance traits and for longevity, were used to test the hologenome hypothesis. We raised flies from all selection regimes, including a regime where flies were kept at benign standard laboratory condition (control regime) throughout the duration of the experiment, under common garden conditions and sequenced the microbiome of the flies. We found abundant differences in microbial communities between control and selection regimes, but not between replicate lines within the regimes, and microbial diversity was higher in selected relative to control lines. Several major core Drosophila bacterial species were differentially abundant in the different selection regimes despite flies being exposed to similar nutritional and general environmental conditions. Our results support the idea that the host and microbiome genomes have evolved in concert and provide experimental support for the hologenome theory of evolution.
Molecular basis for the R-type anion channel QUAC1 activity in guard cells
Authors: Qin Li , Tang Ling-hui , Xu Jia-shu , Zhang Xian-hui , Zhu Yun , Zhang Chun-rui , Liu Xue-lei , Wang Mei-hua , Li Fei , Sun Fei , Su Min , Zhai Yu-jia , Chen Yu-hang 
Published: September 2021

SUMMARYThe rapid (R)-type anion channel plays a central role in controlling stomatal closure in plant guard cells, thus regulating the exchange of water and photosynthetic gas (CO2) in response to environmental stimuli. The activity of the R- type anion channel is regulated by malate. However, the molecular basis of the R-type anion channel activity remains elusive. Here, we describe the first cryo-EM structure of the R-type anion channel QUAC1 at 3.5 Å resolution in the presence of malate. The structure reveals that the QUAC1 is a symmetrical dimer, forming a single electropositive T-shaped pore for passing anions across the membrane. The transmembrane and cytoplasmic domains are assembled into a twisted bi-layer architecture, with the associated dimeric interfaces nearly perpendicular. Our structural and functional analyses reveal that QUAC1 functions as an inward rectifying anion channel and suggests a mechanism for malate-mediated channel activation. Altogether, our study uncovers the molecular basis for a novel class of anion channels and provides insights into the gating and modulation of the R-type anion channel.
Not so local: the population genetics of convergent adaptation in maize and teosinte
Authors: Tittes Silas , Lorant Anne , McGinty Sean , Holland James B. , de Jesus Sánchez-González Jose , Seetharam Arun , Tenaillon Maud , Ross-Ibarra Jeffrey 
Published: September 2021

ABSTRACTWhat is the genetic architecture of local adaptation and what is the geographic scale over which it operates? We investigated patterns of local and convergent adaptation in five sympatric population pairs of traditionally cultivated maize and its wild relative teosinte (Zea mayssubsp.parviglumis). We found that signatures of local adaptation based on the inference of adaptive fixations and selective sweeps are frequently exclusive to individual populations, more so in teosinte compared to maize. However, for both maize and teosinte, selective sweeps are also frequently shared by several populations, and often between subspecies. We were further able to infer that selective sweeps were shared among populations most often via migration, though sharing via standing variation was also common. Our analyses suggest that teosinte has been a continued source of beneficial alleles for maize, even after domestication, and that maize populations have facilitated adaptation in teosinte by moving beneficial alleles across the landscape. Taken together, our results suggest local adaptation in maize and teosinte has an intermediate geographic scale, one that is larger than individual populations but smaller than the species range.
Microtubule-based perception of mechanical conflicts controls plant organ morphogenesis
Authors: Stöckle Dorothee , Reyes-Hernández Blanca Jazmin , Barro Amaya Vilches , Nenadic Milica , Winter Zsófia , Marc-Martin Sophie , Bald Lotte , Ursache Robertas , Fujita Satoshi , Maizel Alexis , Vermeer Joop EM 
Published: September 2021

ABSTRACTPrecise coordination between cells and tissues is essential for differential growth in plants. During lateral root formation in Arabidopsis thaliana, the endodermis is actively remodeled to allow outgrowth of the new organ. Here, we show that microtubule arrays facing lateral root founder cells display a higher order compared to arrays on the opposite wall of the same cell, and this asymmetry is required for endodermal remodeling and lateral root initiation. We identify that MICROTUBULE ASSOCIATED PROTEIN 70-5 is necessary for the establishment of this spatially defined microtubule organization and endodermis remodeling, and thus contributes to lateral root morphogenesis. We propose that MAP70-5 and cortical microtubule arrays in the endodermis integrate the mechanical signals generated by lateral root outgrowth, facilitating the channeling of organogenesis.
Generation and diversification of recombinant monoclonal antibodies for studying mitosis
Authors: DeLuca Keith F. , Mick Jeanne E. , Hodges Amy L. , Lima Wanessa C. , Sherman Lori , Schaller Kristin L. , Anderson Steven M. , Zhao Ning , Stasevich Timothy J. , Varma Dileep , Gorbsky Gary J. , Nilsson Jakob , DeLuca Jennifer G. 
Published: September 2021

AbstractAntibodies are indispensable tools used for a large number of applications in both foundational and translational bioscience research; however, there are drawbacks to using traditional antibodies generated in animals. These include a lack of standardization leading to problems with reproducibility, high costs of antibodies purchased from commercial sources, and ethical concerns regarding the large number of animals used to generate antibodies. To address these issues, we have developed practical methodologies and tools for generating low-cost, high-yield preparations of recombinant monoclonal antibodies and antibody fragments directed to protein epitopes from primary sequences. We describe these methods here, as well as approaches to diversify monoclonal antibodies, including customization of antibody species specificity, generation of genetically encoded small antibody fragments, and conversion of single chain antibody fragments (e.g. scFv) into full-length, bivalent antibodies. This study focuses on antibodies directed to epitopes important for mitotic cell division; however, the methods and reagents described here are applicable to antibodies and antibody fragments for use in any field.
Spexin modulates molecular thermogenic profile of adipose tissue and thermoregulatory behaviors
Authors: Sherman Shermel B. , Gupta Niraj , Harberson Mitchell , Powers Riley , Rashleigh Rebecca , Talla Ramya , Thusu Ashima , Hill Jennifer W. 
Published: September 2021

ABSTRACTThermoregulation is a physiological process by which a mammal regulates body temperature in response to its environment. Within the human body, thermoregulatory behaviors and metabolism are modulated by circulating metabolic factors. In our study, we tested the ability of the neuropeptide spexin, which shares sequence homology to galanin, to regulate these functions in female mice. Supraphysiological levels of spexin in C57BL/6 mice were insufficient to protect against diet-induced obesity after 50 days of treatment. Behavioral analysis of long-term spexin treatment appeared to modulate anxiety-like behaviors by promoting exploratory behaviors and thermoregulatory behaviors of nest building that ceased when animals were housed at thermoneutral temperatures. Upon examination of the molecular profile of brown and white adipose tissue, treatment disrupted the thermogenic profile of white adipose tissue, in which β3-adrenergic receptor expression was downregulated. Our results reveal novel functions for spexin as a modulator of thermoregulatory behaviors and adipose tissue metabolism.HighlightsSpexin treatment did not protect against diet-induced obesity in female mice.Spexin-treatment promoted thermoregulatory behaviors of nest building.Behaviors normalized when animals were housed in thermoneutral temperatures.Funding SourcesNot applicableDisclosure SummaryNothing to disclose
Role of mitotic diffusion barriers in regulating the asymmetric division of activated CD8 T cells
Authors: Emurla Hulya , Barral Yves , Oxenius Annette 
Published: September 2021

SummaryUpon their activation, naïve CD8 T cells divide and differentiate into short-lived effector cells, relevant for exerting immune control, and long-lived memory cells, relevant for long-term immunity. The proportion of memory cells generated depends highly on the context of activation and whether the activated cell divides symmetrically or asymmetrically. However, how T cells control the extent of their asymmetry during their first division in response to contextual signals is not known. Using fluorescence loss in photo-bleaching (FLIP) experiments, we show that the metabolic and plasma membrane asymmetry of mitotic T cells depend on the regulated assembly of a lateral diffusion barrier in their endoplasmic reticulum (ER-) membrane. In asymmetrically dividing T cells, the degrees of asymmetry correlated tightly to barrier strength, whereas symmetrically dividing T cells did not establish such a barrier. Direct positive or negative interference with barrier assembly enhanced or abrogated metabolic and plasma membrane asymmetry, respectively, indicating that barrier strength is a direct and decisive determinant of mitotic asymmetry. Thus, together our data identify diffusion barrier-mediated compartmentalization as a mechanism for how asymmetric T cell regulate their long-term response as a function of the activatory context.
Pharmacological perturbation of intracellular dynamics as a SARS-CoV-2 antiviral strategy
Authors: Bakhache William , Partiot Emma , Lucansky Vincent , Bare Yonis , Bonaventure Boris , Goujon Caroline , Bories Cédric , Deffieu Maika S. , Gaudin Raphael 
Published: September 2021

AbstractSARS-CoV-2 (CoV2) is the viral agent responsible for the pandemic of the coronavirus disease 2019 (COVID-19). Vaccines are being deployed all over the world with good efficacy, but there is no approved antiviral treatment to date. This is particularly needed since the emergence of variants and the potential immune escape may prolong pandemic spreading of the infection for much longer than anticipated. Here, we developed a series of small molecules and identified RG10 as a potent antiviral compound against SARS-CoV-2 in cell lines and human airway epithelia (HAE). RG10 localizes to endoplasmic reticulum (ER) membranes, perturbing ER morphology and inducing ER stress. Yet, RG10 does not associate with SARS-CoV-2 replication sites although preventing virus replication. To further investigate the antiviral properties of our compound, we developed fluorescent SARS-CoV-2 viral particles allowing us to track virus arrival to ER membranes. Live cell imaging of replication-competent virus infection revealed that RG10 stalls the intracellular virus-ER dynamics. Finally, we synthesized RG10b, a stable version of RG10, that showed increased potencyin vitroand in HAE with a pharmacokinetic half-life greater than 2 h. Together, our work reports on a novel fluorescent virus model and innovative antiviral strategy consisting of the perturbation of ER/virus dynamics, highlighting the promising antiviral properties of RG10 and RG10b.
Subclonal evolution and expansion of spatially distinct THY1-positive cells is associated with recurrence in glioblastoma
Authors: Al-Holou Wajd N. , Wang Hanxiao , Ravikumar Visweswaran , Oneka Morgan , Verhaak Roel GW , Kim Hoon , Pratt Drew , Camelo-Piragua Sandra , Speers Corey , Wahl Daniel R , Shankar Sunita , Hollon Todd , Sagher Oren , Heth Jason A , Muraszko Karin M. , Lawrence Theodore S. , de Carvalho Ana C , Mikkelsen Tom , Rao Arvind , Rehemtulla Alnawaz 
Published: September 2021

AbstractPurposeGlioblastoma (GBM) is a lethal disease characterized by inevitable recurrence. Here we investigate the molecular pathways mediating resistance, with the goal of identifying therapeutic opportunities to target this tumor.Experimental DesignWe developed a longitudinal in vivo recurrence model utilizing patient-derived explants to produce paired specimens (pre- and post-recurrence) following temozolomide(TMZ) and radiation(IR). These specimens were evaluated for treatment response and to identify gene expression pathways driving treatment resistance. Findings were clinically validated using spatial transcriptomics of human GBMs.ResultsThese studies reveal in replicate cohorts, a gene expression profile characterized by upregulation of mesenchymal and stem-like genes at recurrence. Analyses of clinical databases revealed increased expression of this transcriptional profile to be significantly associated with worse median overall survival (248 days vs 430 days, p=0.0004), and upregulation of this profile at recurrence. Most notably, we identified upregulation of TGFβ signaling, and more than one-hundred-fold increase in THY1 levels at recurrence. Utilizing cell sorting, we observed that THY1-positive cells represented <10% of cells in the treatment-naïve tumors and 75-96% in the recurrent tumors. We then isolated THY1-positive cells from treatment-naïve patient samples and determined that they were inherently resistant to chemoradiation in orthotopic models. Additionally, using image-guided biopsies from treatment-naïve human GBM, we conducted spatial transcriptomic analyses. This revealed rare THY1+ regions characterized by mesenchymal/stem-like gene expression, analogous to our recurrent mouse model samples, which co-localized with macrophages within the perivascular niche. Since TGFβ signaling contributes to a mesenchymal/stem-like phenotype, we inhibited TGFβRI activity in vivo which resulted in decreased mesenchymal/stem-like protein levels, including THY1, and restored sensitivity to TMZ/IR in recurrent tumors.ConclusionsThese findings reveal that GBM recurrence may result from tumor repopulation by pre-existing, therapy-resistant, THY1-positive, mesenchymal/stem-like cells within the perivascular niche. Furthermore, our data demonstrate the promise of targeting upregulated pathways in resistant subclones as a novel mechanism to achieve therapeutic response, and specifically that THY1 expression may represent a biomarker of response to TGFβ inhibition.
The Role of the Ventrolateral Anterior Temporal Lobes in Social Cognition
Authors: Balgova Eva , Diveica Veronica , Walbrin Jon , Binney Richard J. 
Published: September 2021

AbstractA key challenge for neurobiological models of social cognition is to elucidate whether brain regions are specialised for that domain. In recent years, discussion surrounding the role of anterior temporal regions epitomises such debates; some argue the anterior temporal lobe (ATL) is part of a domain-specific network for social processing, while others claim it comprises a domain-general hub for semantic representation. In the present study, we used ATL-optimised fMRI to map the contribution of different ATL structures to a variety of paradigms frequently used to probe a crucial social ability, namely ‘theory of mind’ (ToM). Using multiple tasks enables a clearer attribution of activation to ToM as opposed to idiosyncratic features of stimuli. Further, we directly explored whether these same structures are also activated by a non-social task probing semantic representations. We revealed that common to all of the tasks was activation of a key ventrolateral ATL region that is often invisible to standard fMRI. This constitutes novel evidence in support of the view that the ventrolateral ATL contributes to social cognition via a domain-general role in semantic processing, and against claims of a specialised social function.
Comparative genomic analysis of skin and soft tissue Streptococcus pyogenes isolates from low- and high-income settings
Authors: Bah Saikou Y. , Keeley Alexander J. , Armitage Edwin P. , Khalid Henna , Chaudhuri Roy R. , Senghore Elina , Manneh Jarra , Tilley Lisa , Marks Michael , Darboe Saffiatou , Sesay Abdul K. , de Silva Thushan I , Turner Claire E. 
Published: September 2021

AbstractStreptococcus pyogenes is a leading cause of human morbidity and mortality, especially in resource limited settings. The World Health Organisation has recently made a vaccine for S. pyogenes a global health priority to reduce the burden of the post-infection rheumatic heart disease. For a vaccine to be active against all relevant strains in each region, molecular characterisation of circulating S. pyogenes isolates is needed. We performed extensive comparative whole genome analyses of S. pyogenes isolates from skin and soft tissue infections in The Gambia, West Africa, where there is a high burden of such infections. To act as a comparator to this low-income country (LIC) collection of isolates, we performed genome sequencing of isolates from skin infections in Sheffield, UK, as representative high-income country (HIC) isolates. LIC isolates from The Gambia were genetically more diverse (46 emm-types in 107 isolates) compared to HIC isolates from Sheffield (23 emm-types in 142 isolates), with only 7 overlapping emm-types and with diverse genetic backgrounds. Characterisation of other molecular markers indicated some shared features, including a high prevalence of the skin infection-associated emm-pattern D and the variable fibronectin-collagen-T antigen (FCT) types FCT-3 and FCT-4. A previously unidentified FCT (FCT-10) was identified in the LIC isolates, belonging to two different emm-types. A high proportion (79/107; 73.8%) of LIC isolates carried genes for tetracycline resistance, compared to 53/142 (37.3%) HIC isolates. There was also evidence of different circulating prophages, as very few prophage-associated DNases and lower numbers of superantigens were detected in LIC isolates. Our study provides much needed insight into the genetics of circulating isolates in a LIC (The Gambia), and how they differ from those circulating in HICs (Sheffield, UK). Common molecular features may act as bacterial drivers for specific infection types, regardless of the diverse genetic background.