bluuebunny/crossref_metadata_2025 huggingface dataset:
Association between Positive Airway Pressure Adherence and Healthcare Costs
Authors: An Jaejin , Glick Henry A. , Sawyer Amy M. , Arguelles Jessica , Bae Charles J. , Chen Aiyu , Keenan Brendan T. , Kuna Samuel T. , Maislin Greg , Mazzotti Diego R. , Pack Allan I. , Shi Jiaxiao M. , Watach Alexa J. , Hwang Dennis
Published: September 2021

Background

The impact of positive airway pressure (PAP) therapy for obstructive sleep apnea (OSA) on healthcare costs is uncertain.

Research Question

Are three-year healthcare costs associated with PAP adherence in participants from the Tele-OSA clinical trial?

Study Design and Methods

Participants with OSA and prescribed PAP in the Tele-OSA study were stratified into three PAP adherence groups based on usage patterns over three years: (a) high (consistently ≥ 4 hours/night); (b) moderate (2-3.9 hours/night or inconsistently ≥ 4 hours/night); (c) low (<2 hours/night). Using data from three months of the Tele-OSA trial and 33 months of post-trial follow-up, average healthcare costs (2020 US dollars) in six-month intervals were derived from electronic health records and analyzed using multivariable generalized linear models.

Results

Of 543 participants, 25% were categorized as having high adherence, 22% moderate adherence, and 52% low adherence to PAP therapy. Average (standard deviation) PAP use was 6.5 (1.0) hours, 3.7 (1.2) hours, and 0.5 (0.5) hours for the high, moderate, and low adherence groups, respectively. The high adherence group had the lowest average [standard error] covariate-adjusted six-month healthcare costs ($3,162 [$240]) compared with the moderate ($3,658 [$369]) and low ($4,016 [$315]) adherence groups. Significant cost savings were observed between the high and low adherence groups ($854 [95% CI $158, $1,551]); savings between moderate and low adherence were non-significant ($359 [95% CI -$459, $1,176]).

Interpretation

In participants with OSA, better PAP adherence was associated with significantly lower healthcare costs over three years. Findings support the importance of strategies to enhance long-term PAP adherence.
A population-specific missense variant rs1597000001 inCETPpromotes a favorable lipid profile and reduces CETP activity
Authors: Moors Jaye , Krishnan Mohanraj , Sumpter Nick , Takei Riku , Bixley Matt , Cadzow Murray , Major Tanya J. , Phipps-Green Amanda , Topless Ruth , Merriman Marilyn , Rutledge Malcolm , Morgan Ben , Carlson Jenna C. , Zhang Jerry Z. , Russell Emily M. , Sun Guangyun , Cheng Hong , Weeks Daniel E. , Naseri Take , Sefuiva Reupena Muagututi‘a , Viali Satupa‘itea , Tuitele John , Hawley Nicola L. , Deka Ranjan , McGarvey Stephen T. , de Zoysa Janak , Murphy Rinki , Dalbeth Nicola , Stamp Lisa , Taumoepeau Mele , King Frances , Wilcox Philip , McCormick Sally , Minster Ryan L. , Merriman Tony R. , Leask Megan
Published: September 2021

Sequencing ofCETPin Māori and Pacific peoples identified a common (MAF ∼2.4%-5.4%) population-specific missense variant (rs1597000001,CETP:c.530C>T p.Pro177Leu) that associates with higher HDL-C levels ([95% CI 0.211; 0.260]) and lower LDL-C ([95% CI -0.209; -0.058]). In a subsample of the study cohort (n = 11), heterozygous carriers of the population-specific variant had lower plasma CETP activity (P= 0.028). Our study identifies a population-specific missense variant inCETPwhich lowers CETP activity with an effect on HDL-C that is comparable to MendelianCETPloss-of-function mutations.
Spike Protein NTD mutation G142D in SARS-CoV-2 Delta VOC lineages is associated with frequent back mutations, increased viral loads, and immune evasion
Authors: Shen Lishuang , Triche Timothy J. , Bard Jennifer Dien , Biegel Jaclyn A. , Judkins Alexander R. , Gai Xiaowu
Published: September 2021

The significantly greater infectivity of the SARS-CoV-2 Delta variants of concern (VOC) is hypothesized to be driven by key mutations that result in increased transmissibility, viral load and/or evasion of host immune response. We surveyed the mutational profiles of Delta VOC genomes between September 2020 and mid-August 2021 and identified a previously unreported mutation pattern at amino acid position 142 in the N-terminal domain (NTD) of the spike protein which demonstrated multiple rounds of mutation from G142 to D142 and back. This pattern of frequent back mutations was observed at multiple time points and across Delta VOC sub-lineages. The etiology for these recurrent mutations is unclear but raises the possibility of host-directed editing of the SARS-CoV-2 genome. Within Delta VOC this mutation is associated with higher viral load, further enhanced in the presence of another NTD mutation (T95I) which was also frequently observed in these cases. Protein modeling of both mutations predicts alterations of the surface topography of the NTD by G142D, specifically disturbance of the ‘super site’ epitope that binds NTD-directed neutralizing antibodies (NAbs). The appearance of frequent and repeated G142D followed by D142G back mutations is previously unreported in SARS-CoV-2 and may represent viral adaptation to evolving host immunity characterized by increasing frequency of spike NAbs, from both prior infection and vaccine-based immunity. The emergence of alterations of the NTD in and around the main NAb epitope is a concerning development in the ongoing evolution of SARS-CoV-2 which may contribute to increased infectivity, immune evasion and ‘breakthrough infections’ characteristic of Delta VOC. Future vaccine and therapy development may benefit by recognizing the emergence of these novel spike NTD mutations and considering their impact on antibody recognition, viral neutralization, infectivity, replication, and viral load.
Refractive-index matching enhanced polarization sensitive optical coherence tomography quantification in human brain tissue
Authors: Liu Chao J. , Ammon William , Jones Robert J. , Nolan Jackson , Wang Ruopeng , Chang Shuaibin , Frosch Matthew P. , Yendiki Anastasia , Boas David A. , Magnain Caroline , Fischl Bruce , Wang Hui
Published: September 2021

The importance of polarization-sensitive optical coherence tomography (PS-OCT) has been increasingly recognized in human brain imaging. Despite the recent progress of PS-OCT in revealing white matter architecture and orientation, quantification of fine-scale fiber tracts in the human brain cortex has been a challenging problem, due to a low birefringence in the gray matter. In this study, we investigated the effect of refractive index matching by 2,2’-thiodiethanol (TDE) immersion on the improvement of PS-OCT measurements inex vivohuman brain tissue. We obtain the cortical fiber orientation maps in the gray matter, which reveals the radial fibers in the gyrus, the U-fibers along the sulcus, as well as distinct layers of fiber axes exhibiting laminar organization. Further analysis shows that index matching reduces the noise in axis orientation measurements by 56% and 39%, in white and gray matter, respectively. Index matching also enables precise measurements of apparent birefringence, which was underestimated in the white matter by 82% but overestimated in the gray matter by 16% prior to TDE immersion. Mathematical simulations show that the improvements are primarily attributed to the reduction in the tissue scattering coefficient, leading to an enhanced signal-to-noise ratio in deeper tissue regions, which could not be achieved by conventional noise reduction methods.
Addiction-Related Memory Transfer and Retention in Planaria
Authors: Samuel Kenneth , Suviseshamuthu Easter S. , Fichera Maria E.
Published: September 2021

Memory retention and transfer in organisms happen at either the neural or genetic level. In humans, addictive behavior is known to pass from parents to offspring. In flatworm planaria (Dugesia tigrina), memory transfer has been claimed to be horizontal, i.e., through cannibalism. Our study is a preliminary step to understand the mechanisms underlying the transfer of addictive behavior to offspring. Since the neural and neurochemical responses of planaria share similarities with humans, it is possible to induce addictions and get predictable behavioral responses. Addiction can be induced in planaria, and decapitation will reveal if the addictive memories are solely stored in the brain. The primary objective was to test the hypothesis that addictive memory is also retained in the brainless posterior region of planaria. The surface preference of the planaria was first determined between smooth and rough surfaces. Through Pavlovian conditioning, the preferred surface was paired with water and the unpreferred surface with sucrose. After the planaria were trained and addicted, their surface preference shifted as a conditioned place preference (CPP) was established. When decapitated, the regenerated segment from the anterior part containing the brain retained the addiction, thus maintaining a shift in the surface preference. Importantly, we observed that the posterior part preserved this CPP as well, suggesting that memory retention is not attributed exclusively to the brain but might also occur at the genetic level. As a secondary objective, the effects of neurotransmitter blocking agents in preventing addiction were studied by administering a D1 dopamine antagonist to planaria, which could provide pointers to treat addictions in humans.
Methylphenidate as a causal test of translational and basic neural coding hypotheses
Authors: Ni Amy M. , Bowes Brittany S. , Ruff Douglas A. , Cohen Marlene R.
Published: September 2021

Most systems neuroscience studies fall into one of two categories: basic science work aimed at understanding the relationship between neurons and behavior, or translational work aimed at developing treatments for neuropsychiatric disorders. Here we use these two approaches to inform and enhance each other. Our study both tests hypotheses about basic science neural coding principles and elucidates the neuronal mechanisms underlying new, clinically relevant behavioral effects of systemically administered methylphenidate (Ritalin). We discovered that orally administered methylphenidate, used clinically to treat Attention Deficit Hyperactivity Disorder (ADHD) and generally to enhance cognition (Lakhan & Kirchgessner, 2012; Maher, 2008), increases spatially selective visual attention, enhancing visual performance at only the attended location. And as predicted by our previous work (Ni et al., 2018), we found that this causal manipulation enhances vision in rhesus macaques specifically when it decreases the mean correlated variability of neurons in visual area V4. Our findings demonstrate that the visual system is a platform for understanding the neural underpinnings of both complex cognitive processes (basic science) and neuropsychiatric disorders (translation). Addressing basic science hypotheses, our results are consistent with a scenario in which methylphenidate has cognitively specific effects by working through naturally selective cognitive mechanisms. Clinically, our findings suggest that the often staggeringly specific symptoms of neuropsychiatric disorders may be caused and treated by leveraging general mechanisms.
Persistent oxidative stress and inflammasome activation in CD14highCD16-monocytes from COVID-19 patients
Authors: Lage Silvia Lucena , Amaral Eduardo Pinheiro , Hilligan Kerry L. , Laidlaw Elizabeth , Rupert Adam , Namasivayan Sivaranjani , Rocco Joseph , Galindo Frances , Kellogg Anela , Kumar Princy , Poon Rita , Wortmann Glenn W. , Shannon John P. , Hickman Heather D. , Lisco Andrea , Manion Maura , Sher Alan , Sereti Irini
Published: September 2021

The poor outcome of the coronavirus disease-2019 (COVID-19), caused by SARS-CoV-2, is associated with systemic hyperinflammatory response and immunopathology. Although inflammasome and oxidative stress have independently been implicated in COVID-19, it is poorly understood whether these two pathways cooperatively contribute to disease severity. Herein, we found an enrichment of CD14highCD16-monocytes displaying inflammasome activation evidenced by caspase-1/ASC-speck formation in severe COVID-19 patients when compared to mild ones and healthy controls, respectively. Those cells also showed aberrant levels of mitochondrial superoxide (MitoSOX) and lipid peroxidation, both hallmarks of the oxidative stress response, which strongly correlated with caspase-1 activity. In addition, we found that NLRP3 inflammasome-derived IL-1β secretion by SARS-CoV-2- exposed monocytesin vitrowas partially dependent on lipid peroxidation. Importantly, altered inflammasome and stress responses persisted after short- term patient recovery. Collectively, our findings suggest oxidative stress/NLRP3 signaling pathway as a potential target for host-directed therapy to mitigate early COVID-19 hyperinflammation as well as its long-term outcomes.
Severe Acute Respiratory Syndrome Coronavirus-2 seropositivity in South-Central Uganda, during 2019 - 2021
Authors: Ssuuna Charles , Galiwango Ronald Moses , Kankaka Edward Nelson , Kagaayi Joseph , Ndyanabo Anthony , Kigozi Godfrey , Nakigozi Gertrude , Lutalo Tom , Ssekubugu Robert , Wasswa John Bosco , Mayinja Anthony , Nakibuuka Martina Cathy , Jamiru Samiri , Oketch John Baptist , Muwanga Edward , Chang Larry William , Grabowski Mary Kate , Wawer Maria , Gray Ronald , Anderson Mark , Stec Michael , Cloherty Gavin , Laeyendecker Oliver , Reynolds Steven James , Quinn Thomas C. , Serwadda David
Published: September 2021

Globally, key subpopulations have a high risk of contracting SARS-CoV-2. In Uganda, limited access to personal protective equipment amidst lack of clarity on the extent of the community disease burden may exacerbate this situation.

We assessed SARS-CoV-2 antibody seroprevalence among high-risk sub-populations, including healthcare workers, persons within the general population previously reporting experiencing key COVID-19 like symptoms and archived plasma specimens collected prior to confirmation of COVID-19 in Uganda.

We collected venous blood from HCWs at selected health facilities and from population-cohort participants who reported specific COVID-19 like symptoms in a prior phone-based survey conducted during the first national lockdown (May-August 2020). Pre-lockdown plasma collected from individuals considered high risk for SARS-CoV-2 infection was retrieved. Specimens were tested for antibodies to SARS-CoV-2 using the CoronaChek™ rapid COVID-19 IgM/IgG lateral flow test assay. IgM only positive samples were confirmed using a chemiluminescent microparticle immunoassay (ARCHITECT AdviseDx SARS-CoV-2 IgM) which targets the spike. SARS-CoV-2 exposure was defined as either confirmed IgM, both IgM and IgG or sole IgG positivity.

The seroprevalence of antibodies to SARS-CoV-2 in HCWs was 21.1% [95%CI: 18.2-24.2]. Of the phone-based survey participants, 11.9% [95%CI: 8.0-16.8] had antibodies to SARS-CoV-2. Among 636 pre-lockdown plasma specimens, 1.7% [95%CI: 0.9-3.1] were reactive.

Findings suggest a high seroprevalence of antibodies to SARS-CoV-2 among HCWs and substantial exposure in persons presenting with specific COVID-19 like symptoms in the general population of South-central Uganda. Based on current limitations in serological test confirmation, it remains unclear whether pre-lockdown seropositivity implies prior SARS-CoV-2 exposure in Uganda.
Adaptation and serial choice bias are unaltered in autism
Authors: Bosch Ella , Fritsche Matthias , Utzerath Christian , Buitelaar Jan K. , de Lange Floris P
Published: September 2021

Autism Spectrum Disorder (ASD) or autism is characterized by social and non-social symptoms, including sensory hyper- and hyposensitivities. A suggestion has been put forward that some of these symptoms could be explained by differences in how sensory information is integrated with its context, including a lower tendency to leverage the past in the processing of new perceptual input. At least two history-dependent effects of opposite directions have been described in the visual perception literature: a repulsive adaptation effect, where perception of a stimulus is biased away from an adaptor stimulus, and an attractive serial choice bias, where perceptual choices are biased towards the previous choice. In this study, we investigated whether autistic participants differed in either bias from typically developing controls (TD). Sixty-four adolescent participants (31 with ASD, 33 TD) were asked to categorize oriented line stimuli in two tasks which were designed so that we would induce either adaptation or serial choice bias. Although our tasks successfully induced both biases, in comparing the two groups, we found no differences in the magnitude of adaptation nor in the modulation of perceptual choices by the previous choice. In conclusion, we find no evidence of a decreased integration of the past in visual perception of autistic individuals.
c-Kit mediates cutaneous sensory axon innervation and multi-kinase inhibitor-induced neurotoxicity
Authors: Tuttle Adam M. , Pomaville Matthew B. , Delgado Katherine C. , Wright Kevin M. , Nechiporuk Alex V.
Published: September 2021

Peripheral somatosensory neurons innervate the skin and sense the environment. Loss of skin innervation, often caused by the “dying back” of distal somatosensory axons, is a common side effect of drug-induced peripheral neuropathies (DIPNs) and results in pain and sensory dysfunction. Targeted cancer therapies frequently employ multi-kinase inhibitor (MKI) drugs that each block multiple receptor tyrosine kinases. Many MKIs produce DIPNs but the molecular targets and cellular mechanisms underlying these are unknown. We performed live-imaging of cutaneous somatosensory axons in larval zebrafish during treatment with several MKIs known to induce DIPNs, and observed axonal retraction consistent with a dying back pathology. These results were replicated in mouse somatosensory neurons. Genetic knockout of potential MKI targets identified c-Kit receptor as a regulator of sensory axon innervation and a major target of these MKIs mediating loss of axonal density. In both fish and mammals, Kit receptor is expressed in cutaneous somatosensory neurons and its ligand, Kitlg, is expressed in the skin. Mosaic misexpression of Kitlg in the skin induced dramatic increases in local sensory axon density, suggesting an important role for Kit signaling in cutaneous axon growth and maintenance. Immunostaining and structure-function analysis revealed Src, a downstream Kit target, mediates Kit’s role in cutaneous axon innervation and MKI neurotoxicity. Our data shows that the Kit-Src signaling pathway has a major role in cutaneous sensory axon innervation and is a potential therapeutic target to address DIPNs caused by MKIs and other compounds.
RUNIMC: An R-based package for imaging mass cytometry data analysis and pipeline validation
Authors: Dolcetti Luigi , Barber Paul R , Weitsman Gregory , Thavaraj Selvam , Ng Kenrick , Chan Julie Nuo En , Patten Piers , Mustapha Rami , Deng Jinhai , Ng Tony
Published: September 2021

We propose a novel pipeline for the analysis of imaging mass cytometry data, comparing an unbiased approach, representing the actual gold standard, with a novel biased method. We made use of both synthetic/ controlled datasets as well as two datasets obtained from FFPE sections of follicular lymphoma, and head and neck patients, stained with a 14 and 29-markers panels respectively. The novel pipeline, denominated RUNIMC, has been completely developed in R and contained in a single package. The novelty resides in the ease with which multi-class random forest classifier can be used to classify image features, making the pathologist’s and expert classification pivotal, and the use of a random forest regression approach that permits a better detection of cell boundaries, and alleviates the necessity of relying on a perfect nuclear staining.
Gli1 regulates the postnatal acquisition of peripheral nerve architecture
Authors: Zotter Brendan , Dagan Or , Brady Jacob , Baloui Hasna , Samanta Jayshree , Salzer James L.
Published: September 2021

Peripheral nerves are organized into discrete cellular compartments. Axons, Schwann cells (SCs), and endoneurial fibroblasts (EFs) reside within the endoneurium and are surrounded by the perineurium - a cellular sheath comprised of layers of perineurial glia (PNG). SC secretion of Desert Hedgehog (Dhh) regulates this organization. In Dhh nulls, the perineurium is deficient and the endoneurium is subdivided into small compartments termed minifascicles. Human Dhh mutations cause a peripheral neuropathy with similar defects. Here we examine the role of Gli1, a canonical transcriptional effector of hedgehog signaling, in regulating peripheral nerve organization. We identify PNG, EFs, and pericytes as Gli1-expressing cells by genetic fate mapping. Although expression of Dhh by SCs and Gli1 in target cells is coordinately regulated with myelination, Gli1 expression unexpectedly persists in Dhh null EFs. Thus, Gli1 is expressed in EFs non-canonically i.e., independent of hedgehog signaling. Gli1 and Dhh also have non-redundant activities. In contrast to Dhh nulls, Gli1 nulls have a normal perineurium. Like Dhh nulls, Gli1 nulls form minifascicles, which we show likely arise from EFs. Thus, Dhh and Gli1 are independent signals: Gli1 is dispensable for perineurial development but functions cooperatively with Dhh to drive normal endoneurial development. During development, Gli1 also regulates endoneurial extracellular matrix production, nerve vascular organization, and has modest, non-autonomous effects on SC sorting and myelination of axons. Finally, in adult nerves, induced deletion of Gli1 is sufficient to drive minifascicle formation. Thus, Gli1 regulates the development and is required to maintain the endoneurial architecture of peripheral nerves.

SIGNIFICANCE STATEMENT

Peripheral nerves are organized into distinct cellular/ECM compartments: the epineurium, perineurium and endoneurium. This organization, with its associated cellular constituents, are critical for the structural and metabolic support of nerves and their response to injury. Here, we show Gli1 - a transcription factor normally expressed downstream of hedgehog signaling - is required for the proper organization of the endoneurium but not the perineurium. Unexpectedly, Gli1 expression by endoneurial cells is independent of, and functions non-redundantly with, Schwann Cell-derived Desert Hedgehog in regulating peripheral nerve architecture. These results further delineate how peripheral nerves acquire their distinctive organization during normal development and highlight mechanisms that may regulate their reorganization in pathologic settings including peripheral neuropathies and nerve injury.
AAV-PHP.S-mediated delivery of reporters to cranial ganglion sensory neurons
Authors: Asencor Andoni I. , Dvoryanchikov Gennady , Tsoulfas Pantelis , Chaudhari Nirupa
Published: September 2021

Because of their ease of use and low risk containment, Adeno-Associated Virus vectors are indispensable tools for much of neuroscience. Yet AAVs have been used relatively little to study the identities and connectivity of peripheral sensory neurons because methods to selectively target particular receptive fields or neuron types have been limited. The introduction of the AAV-PHP.S capsid with selective tropism for peripheral neurons (Chan et al., 2017) offered a solution, which we further elaborate here. We demonstrate using AAV-PHP.S with GFP or mScarlet reporters, that all cranial sensory ganglia, i.e. for cranial nerves V, VII, IX and X, are targeted. Pseudounipolar neurons of both somatic and visceral origin, but not satellite glia, are efficiently transduced rapidly and express the gene of interest within 1 week of injection. Fluorescent reporter proteins are transported into the central and peripheral axons of these sensory neurons, permitting visualization of terminals at high resolution, and/or in intact, cleared brain using light sheet microscopy. By combining a Cre-dependent reporter with the AAV-PHP.S capsid, we confirmed expression in a cell-type dependent manner for both anatomical and targeted functional analyses. The AAV-PHP.S capsid will be a powerful tool for mapping the receptive fields and circuits of molecular subtypes of many somatosensory, gustatory and visceral sensory neurons.

SIGNIFICANCE STATEMENT

AAV vectors have become an essential tool for visualizing, manipulating, and recoding from neurons of the central nervous system. However, the technology is not widely used for peripheral neurons because of several technical limitations. The AAV-PHP.S synthetic capsid, which targets peripheral neurons, was recently introduced (Chan et al., 2017). Here, we establish key parameters for using this virus, including which cells are transduced, the timing of expression in central and peripheral terminals, distant from neuronal somata, and the effectiveness of Cre-dependent constructs for cell type selective expression. This permits the use of AAV for constructing detailed anatomic and functional maps of the projections of molecular subtypes of peripheral sensory neurons.
MICAL1 activation by PAK1 mediates actin filament disassembly
Authors: McGarry David J. , Castino Giovanni , Lilla Sergio , Zanivan Sara , Olson Michael F.
Published: September 2021

The MICAL1 monooxygenase has emerged as an important regulator of filamentous actin (F-actin) structures that contribute to numerous processes including nervous system development, cell morphology, motility, viability and cytokinesis [1–4]. Activating MICAL1 mutations have been linked with autosomal-dominant lateral temporal epilepsy, a genetic syndrome characterized by focal seizures with auditory symptoms [5], emphasizing the need for tight control of MICAL1 activity. F-actin binding to MICAL1 stimulates catalytic activity, resulting in the oxidation of actin methionine residues that promote F-actin disassembly [6, 7]. Although MICAL1 has been shown to be regulated via interactions of the autoinhibitory carboxyl-terminal coiled-coil region [8] with RAB8, RAB10 and RAB35 GTPases [9–12], or Plexin transmembrane receptors [13, 14], a mechanistic link between the RHO GTPase signaling pathways that control actin cytoskeleton dynamics and the regulation of MICAL1 activity had not been established. Here we show that the CDC42 GTPase effector PAK1 serine/threonine kinase associates with and phosphorylates MICAL1 on serine 817 (Ser817) and 960 (Ser960) residues, leading to accelerated F-actin disassembly. Deletion analysis mapped PAK1 binding to the amino-terminal catalytic monooxygenase and calponin domains, distinct from the carboxyl-terminal proteinprotein interaction domain. Stimulation of cells with extracellular ligands including basic fibroblast growth factor (FGF2) led to significant PAK-dependent Ser960 phosphorylation, thus linking extracellular signals to MICAL1 phosphorylation. Moreover, mass spectrometry analysis revealed that co-expression of MICAL1 with CDC42 and active PAK1 resulted in hundreds of proteins increasing their association with MICAL1, including the previously described MICAL1-interacting protein RAB10 [15]. These results provide the first insight into a redox-mediated actin disassembly pathway linking extracellular signals to cytoskeleton regulation via a RHO GTPase family member, and reveal a novel means of communication between RHO and RAB GTPase signaling pathways.
In silico investigation of biomechanical response of a human subjected to primary blast
Authors: Sutar Sunil , Ganpule S. G.
Published: September 2021

The response of the brain to the explosion induced primary blast waves is actively sought. Over the past decade, reasonable progress has been made in the fundamental understanding of bTBI using head surrogates and animal models. Yet, the current understanding of how blast waves interact with the human is in nascent stages, primarily due to lack of data in humans. The biomechanical response in human is critically required so that connection to the aforementioned bTBI models can be faithfully established. Here, using a detailed, full-body human model, we elucidate the biomechanical cascade of the brain under a primary blast. The input to the model is incident overpressure as achieved by specifying charge mass and standoff distance through ConWep. The full-body model allows to holistically probe short- (<5 ms) and long-term (200 ms) brain biomechanical responses. The full-body model has been extensively validated against impact loading in the past. In this work, we validate the head model against blast loading. We also incorporate structural anisotropy of the brain white matter. Blast wave human interaction is modeled using a conventional weapon modeling approach. We demonstrate that the blast wave transmission, linear and rotational motion of the head are dominant pathways for the biomechanical loading of the brain, and these loading paradigms generate distinct biomechanical fields within the brain. Blast transmission and linear motion of the head govern the volumetric response, whereas the rotational motion of the head governs the deviatoric response. We also observe that blast induced head rotation alone produces a diffuse injury pattern in white matter fiber tracts. Lastly, we find that the biomechanical response under blast is comparable to the impact event. These insights will augment laboratory and clinical investigations of bTBI and help devise better blast mitigation strategies.
USP21 deubiquitinase elevates macropinocytosis to enable oncogenic KRAS bypass in pancreatic cancer
Authors: Hou Pingping , Ma Xingdi , Yang Zecheng , Zhang Qiang , Wu Chang-Jiun , Li Jun , Tan Lin , Yao Wantong , Yan Liang , Zhou Xin , Kimmelman Alec C. , Lorenzi Philip L. , Zhang Jianhua , Jiang Shan , Spring Denise , Wang Y. Alan , DePinho Ronald A.
Published: September 2021

Activating mutations in KRAS (KRAS*) are present in nearly all pancreatic ductal adenocarcinoma (PDAC) cases and critical for tumor maintenance. By using an inducible KRAS* PDAC mouse model, we identified a deubiquitinase USP21-driven resistance mechanism to anti-KRAS* therapy. USP21 promotes KRAS*-independent tumor growth via its regulation of MARK3-induced macropinocytosis, which serves to maintain intracellular amino acid levels for anabolic growth. The USP21-mediated KRAS* bypass, coupled with the frequent amplification of USP21 in human PDAC tumors, encourages the assessment of USP21 as a novel drug target as well as a potential parameter that may affect responsiveness to emergent anti-KRAS* therapy.
A method for estimating scheduled and manual override heating behaviour and settings from measurements in low energy UK homes
Authors: Bruce-Konuah Adorkor , Jones Rory V. , Fuertes Alba
Published: September 2021

Purpose

The purpose of this paper is to present a methodology for estimating scheduled and manual override heating events and heating settings from indoor air temperature and gas use measurements in UK homes.

Design/methodology/approach

Living room air temperature and gas use data were measured in ten UK homes built to low energy standards. The temperature measurements are used to establish whether the central heating system is turned on or off and to estimate the heating setpoint used. The estimated heating periods are verified using the homes' average daily gas consumption profiles.

Findings

Using this method, the average number of heating periods per day was 2.2 (SD = 0.8) on weekdays and 2.7 (SD = 0.5) on weekends. The weekday mean heating duration was 8.8 h and for weekends, it was 9.8 h. Manual overrides of the settings occurred in all the dwellings and added an average of 2.4 h and 1.5 h to the heating duration on weekdays and weekends respectively. The mean estimated setpoint temperatures were 21.2 and 21.4°C on weekdays and weekends respectively.

Research limitations/implications

Manual overrides of heating behaviours have only previously been assessed by questionnaire survey. This paper demonstrates an alternative method to identifying these manual override events and responds to a key gap in the current body of research that little is currently reported on the frequency and duration of manual heating overrides in UK homes.

Practical implications

The results could be used to better inform the assumptions of space heating behaviour used in energy models in order to more accurately predict the space heating energy demands of dwellings.

Originality/value

Manual overrides of heating behaviours have only previously been assessed by questionnaire survey. This paper demonstrates an alternative method to identifying these manual override events and responds to a key gap in the current body of research that little is currently reported on the frequency and duration of manual heating overrides in UK homes.
Optimal deep recurrent neural network for sentiment grade classification
Authors: Jasti Sireesha
Published: September 2021

Purpose

Internet has endorsed a tremendous change with the advancement of the new technologies. The change has made the users of the internet to make comments regarding the service or product. The Sentiment classification is the process of analyzing the reviews for helping the user to decide whether to purchase the product or not.

Design/methodology/approach

A rider feedback artificial tree optimization-enabled deep recurrent neural networks (RFATO-enabled deep RNN) is developed for the effective classification of sentiments into various grades. The proposed RFATO algorithm is modeled by integrating the feedback artificial tree (FAT) algorithm in the rider optimization algorithm (ROA), which is used for training the deep RNN classifier for the classification of sentiments in the review data. The pre-processing is performed by the stemming and the stop word removal process for removing the redundancy for smoother processing of the data. The features including the sentiwordnet-based features, a variant of term frequency-inverse document frequency (TF-IDF) features and spam words-based features are extracted from the review data to form the feature vector. Feature fusion is performed based on the entropy of the features that are extracted. The metrics employed for the evaluation in the proposed RFATO algorithm are accuracy, sensitivity, and specificity.

Findings

By using the proposed RFATO algorithm, the evaluation metrics such as accuracy, sensitivity and specificity are maximized when compared to the existing algorithms.

Originality/value

The proposed RFATO algorithm is modeled by integrating the FAT algorithm in the ROA, which is used for training the deep RNN classifier for the classification of sentiments in the review data. The pre-processing is performed by the stemming and the stop word removal process for removing the redundancy for smoother processing of the data. The features including the sentiwordnet-based features, a variant of TF-IDF features and spam words-based features are extracted from the review data to form the feature vector. Feature fusion is performed based on the entropy of the features that are extracted.
Does information technology governance strengthen or weaken contract control in digital platform relationships?
Authors: Yang Qian , Qian Liping , Zhao Xiande
Published: September 2021

Purpose

This study investigates both direct and moderation effects of two dimensions of contract control and information technology governance on platform participants' financial performance.

Design/methodology/approach

Using data collected from 384 platform participants from China's two largest digital platforms, hierarchical regression is used to validate the conceptual model and hypotheses.

Findings

The empirical results show that contract completeness and information technology governance independently improved financial performance, while contract enforcement had an inverted U-shaped effect on financial performance. Furthermore, information technology governance amplified the positive effect of contract completeness, but not of contract enforcement, on financial performance.

Originality/value

This study advances the literature on partnership control by showing the interactive role of information technology governance and contract control. It also enriches research on information technology usage by revealing how information technology governance benefits business partnerships. Finally, it extends transaction cost theory by demonstrating that different dimensions of contracts have different effects on governing interfirm relationships.
Female directors on corporate boards and their impact on corporate social responsibility (CSR): evidence from China
Authors: Khidmat Waqas Bin , Habib Muhammad Danish , Awan Sadia , Raza Kashif
Published: September 2021

Purpose

This study aims to examine the determinants of the female representations on Chinese listed firm’s boards. This study also investigates the effect of gender diversity on corporate social responsibility activities.

Design/methodology/approach

The Tobit regression model is used because the data is censored and using ordinary least square regression can give spurious results. For robust check, the authors also used Heckman’s (1979) two-stage self-selection model to remove the sample self-selection bias.

Findings

The authors find that the female representations on the corporate board are positively associated with firm age, firm performance, corporate governance, family ownership, institutional ownership and managerial ownership while negatively related to firm size and state ownership. This study also incorporates predictors of the critical mass of women on the Chinese listed firm’s board. The study also tests the female-led hypothesis and concludes that the female representation increases in firms with female chief executive officer (CEO) or female chairpersons. The Chinese listed firms with gender-diverse board are socially responsible.

Research limitations/implications

The importance of diversity in corporate boards has been demonstrated in light of the agency theory and the resource dependence framework. The results contribute to the previous literature by documenting the determinants of female representations on board, robust by alternative measures of gender diversity, firm size, corporate governance and estimation techniques.

Practical implications

The economic significance of gender diversity stirred the firms to increase female representation. The policymakers can understand the reasons for female underrepresentation in Chinese boards and can reform the regulation to enhance governance quality, non-state ownership and risk aversion among the listed firms.

Originality/value

This study contributes to the literature by providing empirical evidence on the key predictor of the world’s largest emerging economy, specifically the study focuses on the firm specific determinants, different governance attributes, ownership structure and firm risk measures. This study also seeks to answer if the presence of a female in the Chairperson or CEO position encourages the firms to hire more female directors or not?
Your best buds are worth protecting: Variation in bud protection in a fire‐prone cerrado system
Authors: Chiminazzo Marco Antonio , Bombo Aline Bertolosi , Charles‐Dominique Tristan , Fidelis Alessandra
Published: September 2021

Species growing in fire‐prone savannas usually persist by resprouting from their buds. In this study, we evaluated how various persistence traits allow bud protection for improved survival in fire‐prone ecosystems.

Using an integrative morphological and macroanatomical approach, we analysed how woody plants protect their buds. We tested bud protection at the community level and evaluated: (a) how bud protection changes along a fire frequency gradient, (b) if it differs between shrubs and trees and (c) whether the level of bud protection is related to post‐fire responses of 28 woody savanna species.

A mix of traits involving bud protection may enable woody species persistence in fire‐prone ecosystems. Savanna species better protected their buds than forest species by developing bark and trichomes that allowed resprouting after fire. Regarding growth forms, shrub species capable of resprouting above‐ground had their buds better protected than trees.

Bud protection is not only linked with their position to the bark, but also with the presence of trichomes. Profuse trichomes covering buds were related to savanna species. Some species with no bud protection by bark but with trichomes covering their buds were able to resprout after fire. The presence of accessory buds is also a trait more related to savannas, possibly influencing the resprouting after fire as they are better protected and increase the bud bank. Finally, different persistence traits interact with one another to better protect the buds, requiring a detailed screening of the traits to assess species responses to fire.

Synthesis. During fire, species have their aerial biomass consumed by the flames. To be able to resprout new branches and persist in the environment, they must have well‐protected buds. In this study, we evaluated different ways that woody species protect their buds and related them with their resprouting strategy after fire. We investigated the protection by the bark, the presence of trichomes and accessory buds. By studying the woody community in a gradient of savannas and forests we found that buds can be protected by bark, trichomes or soil. Species can present a mix of these traits and strategies, which enhances their resprouting after fire.

A freePlain Language Summarycan be found within the Supporting Information of this article.
Protein homeostasis, regulation of energy production and activation of DNA damage‐repair pathways are involved in the heat stress response of Pseudogymnoascus spp.
Authors: Abu Bakar Nurlizah , Lau Benjamin Yii Chung , Smykla Jerzy , Karsani Saiful Anuar , Alias Siti Aisyah
Published: September 2021

Proteome changes can be used as an instrument to measure the effects of climate change, predict the possible future state of an ecosystem and the direction in which is headed. In this study, proteomic and gene ontology functional enrichment analysis of six Pseudogymnoascus spp. isolated from various global biogeographical regions were carried out to determine their response to heat stress. In total, 2122 proteins were identified with high confidence. Comparative quantitative analysis showed that changes in proteome profiles varied greatly between isolates from different biogeographical regions. Although the identities of the proteins that changed varied between the different regions, the functions they governed were similar. Gene ontology analysis showed enrichment of proteins involved in multiple protective mechanisms, including the modulation of protein homeostasis, regulation of energy production and activation of DNA damage and repair pathways. Our proteomic analysis did not show any clear relationship between protein changes and the strains' biogeographical origins.
Social mobilization and political change in countries governed by the left: The cases of Argentina and Brazil
Authors: Natalucci Ana , Ferrero Juan Pablo
Published: September 2021

This paper analyses the socio‐political dynamics after the financial crash in two countries governed by the left, Argentina and Brazil. Whilst the economic crisis had an effect on the general distributive capacity of leftwing coalitions, it remains unclear why the political resolution of such a crisis adopted anti‐regime features in Brazil and the form of an institutional alternation of power in Argentina. Our aim is to understand the new socio‐political dynamics and their implications in the crisis of the left turn, especially the relationship between social mobilization and political change in the context of Argentina and Brazil. In doing so, the paper contributes to the growing body of literature interested in the intersections between social movements and the state. Based on the analysis of original qualitative and quantitative data on social protests events in both countries 2011–2015, the paper suggests that the complexity of changes in the socio‐political dynamics can be captured by looking at three dimensions of the problem: grammar of mobilization, social imaginaries, and political representation. The main argument is that the different types of left turn strategy developed in both countries affected in turn the responses to the economic crisis and the new cycle of mobilization. The kirchnerist's movimentista strategy in Argentina contrasted with the demobilizing strategy of the PT in Brazil. Whilst the former contributed to channel the high and polarized levels of activism within the polity, the latter resulted in the crisis of the long cycle of political representation opened with the transition to democracy.
The Project Appropriate Birth: significance of the Robson classification in confronting the caesarean section ‘pandemic’
Authors: Vrachnis N
Published: September 2021

Linked article: This is a mini commentary on D Ferreira D'Agostini Marin et al., pp. 72–80 in this issue. To view this article visit https://doi.org/10.1111/1471‐0528.16919
Establishing determinants and quality indicators for getting home alive following moderate to severe traumatic brain injury: the Australian Traumatic Brain Injury National Data Project
Authors: O'Reilly Gerard M , Curtis Kate , Kim Yesul , Rushworth Nick , Mitra Biswadev , Tee Jin , Hunter Kate , Ryder Courtney , Hendrie Delia , Fitzgerald Mark C
Published: September 2021

Moderate to severe traumatic brain injury (TBI) contributes to a significant burden across Australia. However, the data required to inform targeted equitable system‐level improvements in emergency TBI care do not exist. The incidence and determinants of outcomes following moderate to severe TBI in Australia remain unknown. The variation in the impact of moderate to severe TBI, according to patient demographics and injury mechanism, is poorly defined. The Australian Traumatic Brain Injury National Data Project will lead to a clear understanding, across Australia and pre‐specified subgroups (including Aboriginal and Torres Strait Islander peoples), of the incidence, determinants and impact of priority outcomes following moderate to severe TBI, including survival to discharge home. Furthermore, this project will establish a set of national clinical quality indicators for patients experiencing a moderate to severe TBI. The Australian Traumatic Brain Injury National Data Project will inform where to target emergency care system‐wide improvements. Without baseline data, efforts are wasted.