bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigating the Source of Fatal Pulmonary Thromboembolism in a Coronial Postmortem Population
Authors: Rivers-Kennedy April Dimity , Byard Roger W. , Van Den Heuvel Corinna , Quill Rachael , Langlois Neil E. I. 
Published: February 2022

Abstract
The incidence of how often a deep vein thrombosis is found in the calves of the legs at coronial postmortem examination is unclear. This study retrospectively examined postmortem examination reports from Australian Coronial investigations of sudden death resulting from pulmonary thromboembolism to determine the likelihood of dissection of the deep veins of calves of the legs revealing the source of a pulmonary thromboembolism. From 450 cases taken from the National Coronial Information System (NCIS) for 2016, the postmortem reports of 327 cases were reviewed to provide demographic details of victims of sudden death from pulmonary thromboembolism. In 235 cases, it was possible to determine in 76.6% a thrombus had been found in the deep veins of the calves of the legs after dissection. In 141 cases, it was documented that both sides had been examined. From these, it was determined there was no statistically significant difference in the prevalence of thrombus in either side. However, it was shown that the presence of an abnormality of a lower limb (such as leg or hip infection, burns, surgery and nonoperated fractures, or a larger circumference) increased the likelihood that a deep vein thrombus would be found on that side.
Comprehensive Severe Acute Respiratory Syndrome Coronavirus 2 Detection Using Polymerase Chain Reaction and Rapid Antigen Testing in Postmortem Specimens
Authors: Matsumoto Sari , Takasu Shojiro , Shimmura Suzuka , Sakai Ami , Kanto Yuko , Kanuka Hirotaka , Iwadate Kimiharu 
Published: February 2022

Abstract
Polymerase chain reaction (PCR) is indispensable for diagnosing coronavirus disease 2019 (COVID-19) in autopsy cases. In this study, we performed comprehensive reverse transcription quantitative PCR (RT-qPCR) and rapid antigen tests for COVID-19 on forensic postmortem specimens, regardless of the antemortem symptoms and causes of death. Immediately before forensic external examination and autopsy, a wiping solution was collected from the nasopharynx with a dry swab, and rapid antigen testing and RT-qPCR were performed. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was detected by RT-qPCR in 12 of the 487 cases; the infection rate was 2.46%. Of the RT-qPCR–positive cases, 7 were associated with COVID-19–related deaths. Cycle threshold values were not correlated with the cause of death or postmortem time. The sensitivity and specificity of the rapid antigen test were 91.67% and 100.00%, respectively. The RT-qPCR positivity rate of forensic cases was higher than the cumulative infection rate for the entire population. SARS-CoV-2 could be detected with the rapid antigen test and RT-qPCR within 216 hours of death. Because the rapid antigen test showed the same sensitivity and specificity as those observed in clinical practice, the test combined with RT-qPCR may be useful for diagnosing COVID-19 even in postmortem specimens.
Does the Duration of Perioperative Antibiotic Prophylaxis Influence the Incidence of Postoperative Surgical-Site Infections in Implant-Based Breast Reconstruction in Women with Breast Cancer? A Retrospective Study
Authors: Rothe Kathrin , Münster Nathalie , Hapfelmeier Alexander , Ihbe-Heffinger Angela , Paepke Stefan , Niemeyer Markus , Feihl Susanne , Busch Dirk H. , Kiechle Marion , Brambs Christine E. 
Published: February 2022

Background:
Perioperative antibiotic prophylaxis is an established concept to reduce the risk of surgical-site infections; however, the optimal treatment duration in prosthetic breast reconstruction is still controversial. This study evaluated a potential association between the perioperative antibiotic prophylaxis duration (≤24 hours versus >24 hours) and incidence of postoperative surgical-site infections in immediate implant-based breast reconstruction in breast cancer patients.

Methods:
A descriptive, retrospective analysis of surgical-site infections after immediate implant-based breast reconstruction in breast cancer patients between January of 2011 and December of 2018 was performed. The incidence of postoperative surgical-site infections in patients with more than 24 hours of perioperative antibiotic prophylaxis was compared to patients treated for 24 hours or less.

Results:
A total of 240 patients who met criteria were included. There were no relevant epidemiologic, clinical, or histopathologic differences between groups. Surgical-site infections as defined by the Centers for Disease Control and Prevention criteria occurred in 25.8 percent. A risk factor–adjusted analysis by a prespecified multiple logistic regression model showed that 24 hours or less of perioperative antibiotic prophylaxis was not inferior to treatment for more than 24 hours. The upper limit of the one-sided 95 percent confidence interval of the risk difference was 9.4 percent (below the prespecified noninferiority margin of 10 percent leading to statistical significance). Risk factors for a surgical-site infection included obesity and postoperative wound complications.

Conclusions:
The study found no association between short-course perioperative antibiotic prophylaxis (≤24 hours) and an increased rate of postoperative surgical-site infection. This is of high clinical relevance because short-course treatment can help reduce side effects and the emergence of antimicrobial resistance and prevent surgical-site infections as effectively as a prolonged perioperative antibiotic prophylaxis course.

CLINICAL QUESTION/LEVEL OF EVIDENCE:
Therapeutic, III.
The Effect of Narrow-Band Ultraviolet B Irradiation on the Vascularized Composite Allotransplantation Rat Model
Authors: Huang Ren-Wen , Anggelia Madonna R. , Chuang Wen-Yu , Hsieh Yun-Huan , Cheng Hui-Yun , Lin Cheng-Hung 
Published: February 2022

Introduction
Vascularized composite allotransplantation (VCA) allows functional and esthetic reconstruction for patients with complex anatomical defects. However, acute and chronic graft rejections are significant obstacles to VCA. Ultraviolet light is an oncogenic environmental hazard. However, ultraviolet B (UVB) has an immunomodulation effect. Therefore, this study aims to elucidate the impact of UVB irradiation on the VCA rat model.

Methods
The rat vascularized bone marrow allotransplantation model was used. A vascularized bone marrow from a Brown Norway rat (RT1Ac) was transplanted into a Lewis rat (RT1Ab). The allograft and surrounding abdominal skin were exposed to narrow-band ultraviolet B (NB-UVB) (311 nm) radiation with an energy of 1350 mJ/cm2 3 times a week until the end of the study period. There were 5 study groups: syngeneic transplantation (group 1), allogeneic transplantation (group 2), allogenic transplantation–NB-UVB (group 3), allogenic transplantation–antilymphocyte serum (ALS)–tacrolimus (group 4), and allogenic transplantation–antilymphocyte serum–tacrolimus–NB-UVB (group 5).

Results
Group 5 had decreased graft survival compared with group 4. In the donor cell chimerism analysis, donor cell chimerism decreased significantly after UVB irradiation and was unresponsive to the administered immunosuppressants. After UVB irradiation, the CD8 T-cell ratio was increased, and the regulatory T-cell ratio was decreased.

Conclusions
The preliminary data showed that NB-UVB irradiation of the VCA rat model may decrease graft survival. However, further studies are needed to elucidate the possible mechanisms of this phenomenon.
The Age-Related Probability of Dying from COVID-19 among Those Infected: A Relative Survival Analysis
Authors: Swanson David A. , Poston Dudley , Krantz Steven G. , Rao Arni S.R. Srinivasa 
Published: February 2022

AbstractBackgroundCOVID-19 was first identified in Wuhan, the capital city of the province of Hubei in China. Due to the presentation of multiple symptoms at the same time, it is clinically important to understand the probability of dying from COVID-19 vs. the probability of dying from other causes.MethodsUsing data collected in Hubei that identified by age those who died of COVID-19 or its sequelae among the infected, we constructed a life table showing the conditional probability of dying at age x from COVID-19 and its sequela among those infected. Following the relative survival perspective, we also computed corresponding data for China that matched the format of the life table we constructed from the Hubei study. We then formed ratios of the 10-year conditional portability of dying at age x from COVID-19 for the Hubei COVID-19 victims to the ten-year conditional probability of dying at age x from all non-COVID-19 causes for those not infected by COVID-19 in China as a whole.FindingsAt every age, the conditional probability of dying from COVID-19 among those infected in Hubei is higher than the conditional probability of dying from all non-COVID-19 causes for China as a whole. Following a general age-related mortality pattern, the conditional probability of dying from COVID-19 from age 20 onward increases monotonically for those who are infected. Relative to the probability of dying in China from all other causes for those not infected, however, it declines monotonically from age 20 to age 70.InterpretationAt younger ages the relative conditional probability of dying from CVOD-19 among the infected is substantially higher than it is for those infected who dying of all other causes and while staying higher at all ages, it declines monotonically with age. The monotonic decline in the ratio from age 20 to age 70 is a result of the age-related increase in the probability of dying from one or more of a number of competing causes, which, in the case at hand is manifested in the fact that non-COVID-19 deaths in China among the uninfected were generally increasing at a faster age-related rate than were the COVID-19 deaths to the infected in Hubei.
Heightened NLRP3 inflammasome activation is associated with aging and CMML diseases severity
Authors: Andina Nicola , de Meuron Louise , Schnegg-Kaufmann Annatina Sarah , Ansermet Camille , Bomaci Giuseppe , Keller Nino , Porret Naomi , Angelillo-Scherrer Anne , Bonadies Nicolas , Allam Ramanjaneyulu 
Published: February 2022

AbstractAging causes chronic low-grade inflammation known as inflamm-aging. It is a risk factor for chronic myelomonocytic leukemia (CMML), a hematological malignancy that is most prevalent in older people. Recent studies suggest a critical role for the NLRP3 inflammasome in inflamm-aging. However, the mechanisms involved in NLRP3 activation in aging and its involvement in CMML progression are not fully understood. Here, we report that aging increases interleukin-1β production upon NLRP3 activation in human CD14+ monocytes. Interestingly, we found that Toll-like receptor (TLR) 1/2 agonist Pam3Cysk4 directly activates NLRP3 inflammasome without the requirement of second activation signal in monocytes from older but not from younger healthy donors. Further, we observed a dichotomous response to NLRP3 inflammasome activation in monocytes from CMML patients. Intriguingly, CMML patients with heightened NLRP3 activation showed increased treatment dependency and disease severity. Collectively, our results suggest that aging causes increased sensitivity to NLRP3 inflammasome activation at cellular level, which may explain increased inflammation and immune dysregulation in older individuals. Furthermore, NLRP3 inflammasome activation was dysregulated in CMML and positively correlated with disease severity.
Ornithine Lipid is a Partial TLR4 Agonist and NLRP3 Activator
Authors: Pizzuto Malvina , Hurtado-Navarro Laura , Molina-Lopez Cristina , Soubhye Jalal , Gelbcke Michel , Rodriguez-Lopez Silvia , Ruysschaert Jean-Marie , Schroder Kate , Pelegrin Pablo 
Published: February 2022

AbstractMyeloid cells recognise Gram-negative bacterial lipopolysaccharides (LPS). LPS recognition triggers inflammatory reactions through Toll-like receptor 4 (TLR4) and primes the cells for inflammasome activation. In phosphate-depleted environments, bacteria cannot produce LPS. Instead, they increase their synthesis of ornithine lipid (OL), which is constitutively present in some pathogenic Gram-negative and -positive bacteria but absent in commensals. OL is implicated in bacterial pathogenicity, but the mechanism is unclear. Using primary murine macrophages and human peripheral blood mononuclear cells, we identify OL as a partial TLR4 agonist and an NLRP3 inflammasome activator. For this, OL directly activates TLR4 and indirectly activates NLRP3 in a potassium-efflux-dependent manner. OL also upregulates the expression of NLRP3 and pro-IL-1β and induces cytokine secretion in primed and unprimed cells. By contrast, in the presence of LPS, OL functions as a partial TLR4 antagonist; LPS-induced TLR4 activation and inflammasome priming are inhibited by OL, leading to reduced TNF and IL-1β secretion. We thus suggest that in phosphate-depleted environments, OL replaces LPS bacterial immunogenicity while constitutively present OL may allow bacteria to escape immune surveillance.
Lactate Transport and Signaling Mediated by AMD3100 Ameliorates Astrocyte Pathology and Remyelination Without Additional Extension of SOD1G93A Mice’ Life-Span
Authors: Rabinovich-Nikitin Inna , Solomon Beka 
Published: February 2022

AbstractBackgroundAmyotrophic lateral sclerosis (ALS) is characterized by the progressive degeneration of motor neurons accompanied by the accumulation of the morphologically and functionally altered glial cells. Reactive astrocytes and microglia secrete pro-inflammatory mediators and contribute to disease progression. Notably, oligodendrocyte functions are disrupted in ALS, including trophic support, myelination, and oligodendrocyte differentiation. ALS patients and mutant SOD1 mice models display reduced levels of myelin basic protein (MBP) and monocarboxylate transporter 1 (MCT1) contributing to impairment of oligodendrocyte function. Lactate, an active metabolite capable of moving into or out of cells, acts as a signaling molecule, transported exclusively by monocarboxylate transporters (MCTs). We showed previously, that AMD3100 increases the lactate transporter MCT1 in an animal models of Alzheimer’s disease (AD) and ALS.Methods and ResultsAMD3100 is a reversible antagonist of CXCR4, and therefore inhibits the CXCR4/CXCL12 axis. AMD3100 was shown to have beneficial effects on extension of SOD1G93A mice’ life-span and enabling migration of hematopoietic stem cells (HSPCs) from bone marrow to periphery. The low content of lactate and transporters in SOD1G93A mice model led us to propose a combined treatment with AMD3100 and exogeneous L-lactate.ConclusionsThe combined treatment attenuated neuroinflammation and remyelination but did not have a significant extension of SOD1G93A mice’ life-span compared with AMD3100 treatment alone.
Making sense of disorder: Investigating intrinsically disordered proteins in the tardigrade proteome via a computational approach
Authors: Lowe Nora E. , Chang Roger L. 
Published: February 2022

AbstractTardigrades, also known as water bears, are a phylum of microscopic metazoans with the extraordinary ability to endure environmental extremes. When threatened by suboptimal habitat conditions, these creatures enter a suspended animation-like state called cryptobiosis, in which metabolism is diminished, similar to hibernation. In this state, tardigrades benefit from enhanced extremotolerance, withstanding dehydration efficiently for years at a time in a type of cryptobiosis called anhydrobiosis. Recent studies have demonstrated that the tardigrade proteome is at the heart of cryptobiosis. Principally, intrinsically disordered proteins (IDPs) and tardigrade-specific intrinsically disordered proteins (TDPs) are known to help protect cell function in the absence of water. Importantly, TDPs have been successfully expressed in cells of other species experimentally, even protecting human tissue against stressin vitro. However, previous work has failed to address how to strategically identify TDPs in the tardigrade proteome holistically. The overarching purpose of this current study, consequently, was to generate a list of IDPs/TDPs associated with tardigrade cryptobiosis that are high-priority for further investigation. Firstly, a novel database containing 44,836 tardigrade proteins from 338 different species was constructed to consolidate and standardize publicly available data. Secondly, a support vector machine (SVM) was created to sort the newly constructed database entries on the binary basis of disorder (i.e., IDP versus non-IDP). Features of this model draw from disorder metrics and literature curation, correctly classifying 160 of the 171 training set proteins (~93.6%). Of the 5,415 putative IDPs/TDPs our SVM identified, we present 82 (30 having confident subclass prediction and 52 having experimental detection in previous studies). Subsequently, the role each protein might play in tardigrade resilience is discussed. By and large, this supervised machine learning classifier represents a promising new approach for identifying IDPs/TDPs, opening doors to harness the tardigrade’s remarkable faculties for biomaterial preservation, genetic engineering, astrobiological research, and ultimately, the benefit of humankind.
CRISPR/Cas9 gene editing uncovers the role of CTR1 and ROS1 in melon fruit ripening and epigenetic regulation
Authors: Giordano Andrea , Domingo Miguel Santo , Quadrana Leandro , Pujol Marta , Martín-Hernández Ana Montserrat , Garcia-Mas Jordi 
Published: February 2022

AbstractMelon (Cucumis melo L.) has emerged as an alternative model to study fruit ripening due to the coexistence of climacteric and non-climacteric varieties. The previous characterization of a major QTL ETHQV8.1 sufficient to trigger climacteric ripening in a non-climacteric background allowed the identification within the QTL interval of a negative regulator of ripening CmCTR1-like (MELO3C024518), and a putative DNA demethylase CmROS1 (MELO3C024516), the orthologue of DML2, a DNA demethylase regulating fruit ripening in tomato. To understand the role of these genes in climacteric ripening, we generated homozygous CRISPR knockout mutants of CmCTR1-like and CmROS1 in a climacteric genetic background. The climacteric behavior was altered in both loss-of-function mutants in two summer seasons with an advanced ethylene production profile compared to the climacteric wild type, suggesting a role of both genes in climacteric ripening in melon. Single cytosine methylome analyses of the CmROS1 knockout mutant revealed DNA methylation changes in the promoter regions of key ripening genes as ACS1, ETR1 and ACO1, and ripening associated-transcription factors as NAC-NOR, RIN and CNR, suggesting the importance of CmROS1-mediated DNA demethylation for triggering fruit ripening in melon.
Enrichment of specific GABAergic neuronal types in the mouse perirhinal cortex
Authors: Nigro Maximiliano José , Kjelsberg Kasper , Convertino Laura , Nair Rajeevkumar Raveendran , Witter Menno P. 
Published: February 2022

AbstractGABAergic neurons represent 10-15% of the neuronal population of the cortex but exert a powerful control over information flow in cortical circuits. GABAergic neurons show an extraordinary diversity in their morphology, physiology, molecular markers and connectivity. This diversity allows GABAergic neurons to participate in a wide variety of microcircuit motifs. The diversity of GABAergic neurons has been shown to be conserved across cortical regions. The GABAergic population can be broadly divided in three major classes parvalbumin, somatostatin and 5HT3aR groups. The largest GABAergic class in the cortex is represented by the parvalbumin-expressing fast-spiking neurons, which provide powerful somatic inhibition to their postsynaptic targets. Recently, the density of parvalbumin-expressing neurons has been shown to be lower in associative areas of the mouse cortex, including the perirhinal cortex, as compared to sensory and motor areas. In the present study we investigated whether this reduction in parvalbumin-expressing neurons leads to a decreased GABAergic population, or to an enrichment of other GABAergic cell-types. We found that the GABAergic population of the perirhinal cortex is comparable to that of a primary sensory area, and it is enriched of neurons belonging to the 5HT3aR group. We also demonstrate that, despite the low density of parvalbumin-expressing neurons, the perirhinal cortex contains a comparable population of fast-spiking neurons, most of which do not express parvalbumin. Our results demonstrate a yet uncharacterized diversity within the fast-spiking population across cortical regions.
A critical test of deep convolutional neural networks’ ability to capture recurrent processing in the brain using visual masking
Authors: Loke Jessica , Seijdel Noor , Snoek Lukas , van der Meer Matthew , van de Klundert Ron , Quispel Eva , Cappaert Natalie , Scholte H. Steven 
Published: February 2022

AbstractRecurrent processing is a crucial feature in human visual processing supporting perceptual grouping, figure-ground segmentation, and recognition under challenging conditions. There is a clear need to incorporate recurrent processing in deep convolutional neural networks (DCNNs) but the computations underlying recurrent processing remain unclear. In this paper, we tested a form of recurrence in deep residual networks (ResNets) to capture recurrent processing signals in the human brain. Though ResNets are feedforward networks, they approximate an excitatory additive form of recurrence. Essentially, this form of recurrence consists of repeating excitatory activations in response to a static stimulus. Here, we used ResNets of varying depths (reflecting varying levels of recurrent processing) to explain electroencephalography (EEG) activity within a visual masking paradigm. Sixty-two humans and fifty artificial agents (10 ResNet models of depths - 4, 6, 10, 18 and 34) completed an object categorization task. We show that deeper networks (ResNet-10, 18 and 34) explained more variance in brain activity compared to shallower networks (ResNet-4 and 6). Furthermore, all ResNets captured differences in brain activity between unmasked and masked trials, with differences starting at ∼98ms (from stimulus onset). These early differences indicated that EEG activity reflected ‘pure’ feedforward signals only briefly (up to ∼98ms). After ∼98ms, deeper networks showed a significant increase in explained variance which peaks at ∼200ms, but only within unmasked trials, not masked trials. In summary, we provided clear evidence that excitatory additive recurrent processing in ResNets captures some of the recurrent processing in humans.Significance statementThe challenge of modeling recurrent processes is not trivial and the operationalization of recurrent processing is highly contested. In this paper, we tested the ability of deep residual networks (ResNets) to explain recurrent processes in the human brain. Though ResNets are feedforward networks, they have been shown to equate operations in recurrent neural networks. In this study, we show that deeper networks explained more variance in brain activity than shallower networks. However, all networks still performed far from the noise ceiling. Thus, we conclude that recurrent processing in ResNets captures a form of recurrent processing in humans though other types of recurrent processing (inhibition, multiplicative) that are not present in current regular deep neural networks (alexnet, cornet, resnet) are necessary for building better visual models.