bluuebunny/crossref_metadata_2025_split huggingface dataset:
Zinc protection of fertilized eggs is an ancient feature of sexual reproduction in animals
Authors: Wozniak Katherine L. , Bainbridge Rachel E. , Summerville Dominique W. , Tembo Maiwase , Phelps Wesley A. , Sauer Monica L. , Wisner Bennett W. , Czekalski Madelyn E. , Pasumarthy Srikavya , Hanson Meghan L. , Linderman Melania B. , Luu Catherine H. , Boehm Madison E. , Sanders Steven M. , Buckley Katherine M. , Bain Daniel J. , Nicotra Matthew L. , Lee Miler T. , Carlson Anne E. 
Published: June 2020

AbstractOne of the earliest and most prevalent barriers to successful reproduction is polyspermy, or fertilization of an egg by multiple sperm. To prevent these supernumerary fertilizations, eggs have evolved multiple mechanisms. It has recently been proposed that zinc released by mammalian eggs at fertilization may block additional sperm from entering. Here, we demonstrate that eggs from amphibia and teleost fish also release zinc. UsingXenopus laevisas a model, we document that zinc reversibly blocks fertilization. Finally, we demonstrate that extracellular zinc similarly disrupts early embryonic development in eggs from diverse phyla, including: Cnidaria, Echinodermata, and Chordata. Our study reveals that a fundamental strategy protecting human eggs from fertilization by multiple sperm may have evolved more than 650 million years ago.
Increased demand for NAD+ relative to ATP drives aerobic glycolysis
Authors: Luengo Alba , Li Zhaoqi , Gui Dan Y. , Sullivan Lucas B. , Zagorulya Maria , Do Brian T. , Ferreira Raphael , Naamati Adi , Ali Ahmed , Lewis Caroline A. , Thomas Craig J. , Spranger Stefani , Matheson Nicholas J. , Vander Heiden Matthew G. 
Published: June 2020

AbstractAerobic glycolysis, or preferential fermentation of glucose-derived pyruvate to lactate despite available oxygen, is a hallmark of proliferative metabolism that is observed across many organisms and conditions. To better understand why aerobic glycolysis is associated with cell proliferation, we examined the metabolic consequence of activating the pyruvate dehydrogenase complex (PDH) to increase mitochondrial pyruvate oxidation at the expense of fermentation. We find that increasing PDH activity impairs cell proliferation by reducing the nicotinamide adenine dinucleotide cofactor ratio (NAD+/NADH). This change in NAD+/NADH ratio is caused by an increase in mitochondrial membrane potential that impairs mitochondrial electron transport and NAD+ regeneration. Uncoupling mitochondrial respiration from ATP synthesis or increasing ATP hydrolysis restores NAD+/NADH homeostasis and proliferation even when glucose oxidation is increased. These data suggest that when the demand for NAD+ to support oxidation reactions exceeds the demand for ATP consumption in cells, NAD+ regeneration by mitochondrial respiration becomes constrained, promoting fermentation despite available oxygen. This argues that cells engage in aerobic glycolysis when the cellular demand for NAD+ is in excess of the cellular demand for ATP.
Dietary sphinganine is selectively assimilated by members of the gut microbiome
Authors: Lee Min-Ting , Le Henry H. , Johnson Elizabeth L. 
Published: June 2020

AbstractFunctions of the gut microbiome have a growing number of implications for host metabolic health, with diet being one of the most significant influences on microbiome composition. Compelling links between diet and the gut microbiome suggest key roles for various macronutrients, including lipids, yet how individual classes of dietary lipids interact with the microbiome remain largely unknown. A class of lipids known as sphingolipids are bioactive components of most foods and are produced by prominent gut microbes. This makes sphingolipids intriguing candidates for shaping diet-microbiome interactions. Here, we use a click-chemistry based approach to track the incorporation of bioorthogonal dietary omega-alkynyl sphinganine (sphinganine alkyne – SAA) into the gut microbial community (Click). Identification of microbe and SAA-specific metabolic products was achieved by fluorescence-based sorting of SAA containing microbes (Sort), 16S rRNA gene sequencing to identify the sphingolipid-interacting microbes (Seq), and comparative metabolomics to identify products of SAA assimilation by the microbiome (Spec). Together this approach, Click-Sort-Seq-Spec (ClickSSS), revealed that SAA-assimilation was nearly exclusively performed by gutBacteroides, indicating that sphingolipid-producing bacteria play a major role in processing dietary sphinganine. Comparative metabolomics of cecal microbiota from SAA-treated mice showed conversion of SAA to a suite of dihydroceramides, consistent with metabolic activity viaBacteroidesandBifidobacterium. Additionally, other sphingolipid-interacting microbes were identified with a focus on an uncharacterized ability ofBacteroidesandBifidobacteriumto metabolize dietary sphingolipids. Therefore, ClickSSS provides a platform to study the flux of virtually any alkyne-labeled metabolite in diet-microbiome interactions.
Monet: An open-source Python package for analyzing and integrating scRNA-Seq data using PCA-based latent spaces
Authors: Wagner Florian 
Published: June 2020

AbstractSingle-cell RNA-Seq is a powerful technology that enables the transcriptomic profiling of the different cell populations that make up complex tissues. However, the noisy and high-dimensional nature of the generated data poses significant challenges for its analysis and integration. Here, I describeMonet, an open-source Python package designed to provide effective and computationally efficient solutions to some of the most common challenges encountered in scRNA-Seq data analysis, and to serve as a toolkit for scRNA-Seq method development. At its core, Monet implements algorithms to infer the dimensionality and construct a PCA-based latent space from a given dataset. This latent space, represented by aMonetModelobject, then forms the basis for data analysis and integration. In addition to validating these core algorithms, I provide demonstrations of some more advanced analysis tasks currently supported, such as batch correction and label transfer, which are useful for analyzing multiple datasets from the same tissue. Monet is available athttps://github.com/flo-compbio/monet. Ongoing work is focused on providing electronic notebooks with tutorials for individual analysis tasks, and on developing interoperability with other Python scRNA-Seq software. The author welcomes suggestions for future improvements.
Aging interacts with tumor biology to produce major changes in the immune tumor microenvironment
Authors: Erbe Rossin , Wang Zheyu , Zaidi Neeha , Topper Michael , Baylin Stephen , Jaffee Elizabeth M , Easwaran Hariharan , Fertig Elana J 
Published: June 2020

AbstractAdvanced age is strongly correlated with both increased cancer incidence and general immune decline. The immune tumor microenvironment (ITME) has been established as an important prognostic of both therapeutic efficacy and overall patient survival. Thus, age-related immune decline is an important consideration for the treatment of a large subset of cancer patients. Current studies of aging-related immune alterations are predominantly performed on non-cancerous tissue, requiring additional study into the effects of age on tumor immune infiltration. We leverage large scale transcriptional data sets from The Cancer Genome Atlas and the Genotype-Tissue Expression project to distinguish normal age-related immune alterations from age-related changes in tumor immune infiltration. We demonstrate that while there is overlap between the normal immune aging phenotype and that of the ITME, there are several changes in immune cell abundance that are specific to the ITME, particularly in T cell, NK cell, and Macrophage populations. These results suggest that aged immune cells are more susceptible to tumor suppression of cytotoxic immune cell infiltration and activity than normal tissues, which creates an unfavorable ITME in older patients in excess of normal immune decline with age and may inform the application of existing and emerging immunotherapies for this large population of patients. We additionally identify that age-related increases in tumor mutational burden are associated with decreased DNA methylation and increased expression of the immune checkpoint genesPDL1, CD80,andLAG3which may have implications for therapeutic application of immune checkpoint blockade in older patients.
Caffeine decreases neuromuscular fatigue in the lumbar muscles – a randomized blind study
Authors: Cardoso Liziane , Nery Tatyana , Gonçalves Maielen , Carolina Speck Maria , de Bem Alves Ana Cristina , Bristot Viviane , Gonçalves Thais , Scheffer Débora da Luz , Schneider Ione Jayce Ceola , Kuriki Heloyse , S Aguiar Aderbal 
Published: June 2020

ABSTRACTBackgroundErgogenic evidence for caffeine is robust in sports and isolated limb tasks. Our objective was to evaluate a possible ergogenic effect on postural muscles, still unknown, through the Biering-Sørensen’s lumbar extension test.MethodsA double-blind, controlled placebo, crossover study. Fifty-one healthy, physically inactive male subjects (18-25 years) with average body mass (BMI 18.5 – 24.9 kg/m2) were recruited. The subjects received oral caffeine (6 mg/kg) and saline (0.3%) in two cross-evaluations separated by one week. The primary outcome was the time in the Biering-Sørensen test after 1 hour of treatment. The secondary outcomes were peak lumbar extension force, rating of perceived exertion, EMG’s median frequency and muscle recruitment of multifidus spinae and transversalis/interne oblique muscles, and cardiovascular variables (heart rate and blood pressure).Results27 subjects were blindly treated with caffeine and saline. Caffeine was ergogenic during the Biering-Sørensen test. It increased lumbar extension time (d = 0.34, P<0.05), but not peak force. The perception of effort decreased with caffeine (d = 0.37, P<0.05). Caffeine increased muscle stimulation frequency (P<0.05) and recruitment (η2 = 0.49, P<0.05) of multifidus spinae. In the transversalis/interne oblique muscles, caffeine increased the median frequency η2 = 0.13, P<0.05) and the distribution of higher frequencies (P<0.05). Caffeine also increased muscle recruitment in the transversalis/interne oblique muscles η2 = 0.13, P<0.05) Tachycardia and increased blood pressure at the lumbar test were higher in the caffeine condition (P< 0.05).ConclusionsOur results show that caffeine is ergogenic for postural muscles. Decreased RPE and improved muscle activity suggest central mechanisms of caffeine.Trial registrationUTN U1111-1234-2079.BULLET POINTSCaffeine increases the extension time of the lumbar spine in the Biering-Sørensen test.Caffeine decreases perceived exertion during the Biering-Sørensen test.Caffeine increases muscle stimulation and recruitment of the multifidus spinae during the Biering-Sørensen test.Caffeine increases muscle stimulation of the transversalis/interne oblique muscles during the Biering-Sørensen test.
Development and validation of a potential salivary biomarker panel for Oral Squamous Cell Carcinoma
Authors: Jain Anu , Kotimoole Chinmaya Narayana , Ghoshal Sushmita , Bakshi Jaimanti , Chatterjee Aditi , Keshav Prasad Thottethodi Subrahmanya , Pal Arnab 
Published: June 2020

AbstractPurposeOral Squamous Cell Carcinoma (OSCC) is one of the most prevalent cancers in the world with maximum number of cases reported from India. Poor survival rate associated with OSCC can be attributed to non-availability of a biomarker, as one of the major reasons, leading to late presentation. Identification of an early diagnostic biomarker, which can also be used as a screening tool, will be helpful in reducing the disease morbidity and mortality.Experimental DesignIn this article we report Parallel Reaction Monitoring (PRM) based validation of 12 candidate proteins, identified initially by TMT tag based relative quantification of salivary proteins on LC-MS, in the saliva of Oral Squamous Cell Carcinoma (OSCC) cases (N=50) and healthy controls (N=49), AZGP1, AHSG, KRT6C, S100A7, S100A9, KLK1, BPIFB2, IGLL5, CORO1A, LACRT, LCN2 and PSAP. Heavy isotope labelled reference peptides were used to produce calibration curve and absolute quantification of proteins and resulting data was analyzed statistically using R.ResultsSalivary AHSG (p=0.0041**) and KRT6C (p=0.002**) were significantly upregulated in OSCC cases while AZGP1 (p=<0.0001***), KLK1 (p=0.006**) and BPIFB2 (p=0.0061**) were significantly downregulated. Multivariate logistic regression modelling resulted in a risk prediction model consisting of AZGP1, AHSG and KRT6C with p value <0.0001***. Using this model ROC with area under the curve of 82.2% was produced and sensitivity and specificity observed for this model was 78% and 73.5%. Positive and negative predictive values for the model were 76% and 75% respectively.ConclusionWe report a potential biomarker panel consisting of proteins AZGP1, AHSG and KRT6C for early diagnosis of OSCC.
Principles and Practice of SARS-CoV-2 Decontamination of N95 Masks with UV-C
Authors: Huber Thomas , Goldman Olivia , Epstein Alexander E. , Stella Gianna , Sakmar Thomas P. 
Published: June 2020

AbstractA mainstay of personal protective equipment (PPE) during the COVID-19 pandemic is the N95 filtering facepiece respirator. N95 respirators are commonly used to protect healthcare workers from respiratory pathogens, including the novel coronavirus SARS-CoV-2, and are increasingly employed by other frontline workers and the general public. Under routine circumstances, these masks are disposable, single-use items, but extended use and reuse practices have been broadly enacted to alleviate critical supply shortages during the COVID-19 pandemic. While extended-time single use presents a low risk of pathogen transfer, repeated donning and doffing of potentially contaminated masks presents increased risk of pathogen transfer. Therefore, efficient and safe decontamination methods for N95 masks are needed to reduce the risk of reuse and mitigate local supply shortages. Here we review the available literature concerning use of germicidal ultraviolet-C (UV-C) light to decontaminate N95 masks. We propose a practical method for repeated point-of-use decontamination using commercially-available UV-C crosslinker boxes from molecular biology laboratories to expose each side of the mask to 800–1200 mJ/cm2of UV-C. We measure the dose that penetrated to the interior of the respirators and model the potential germicidal action on SARS-CoV-2. Our experimental results, in combination with modeled data, suggest that a two-minute UV-C treatment cycle should induce a >3-log-order reduction in viral bioburden on the surface of the respirators, and a 2-log order reduction throughout the interior. The resulting exposure is 100-fold less than the dose expected to damage the masks, facilitating repeated decontamination. As such, UV-C germicidal irradiation (UVGI) is a practical strategy for small-scale point-of-use decontamination of N95s.
The association between thrombocytosis and subtype of lung cancer: a systematic review and meta-analysis
Authors: Barlow Melissa , Hamilton Willie , Ukoumunne Obioha Chukwunyere , Bailey Sarah Elizabeth Rose 
Published: June 2020

ABSTRACTBackgroundThrombocytosis is associated with poor lung cancer prognosis and has recently been identified as having a high predictive value in lung cancer detection. Lung cancer has multiple histological and genetic subtypes and it is not known whether platelet levels differ across subtypes.MethodsPubMed and Embase were systematically searched for studies that reported pre-treatment platelet count, as either averages or proportion of patients with thrombocytosis, by histological subtype of lung cancer. Suitable studies were synthesised in meta-analyses; subgroup analyses examined for differences across subtypes.ResultsThe prevalence of pre-treatment thrombocytosis across all lung cancer patients was 27% (95% CI: 17 to 37%). By subtype, this was 22% (95% CI: 7 to 41%) for adenocarcinoma (ADC), 28% (95% CI: 15 to 43%) for squamous cell carcinoma (SCC), 36% (95% CI: 13 to 62%) for large cell carcinoma, and 30% (95% CI: 8 to 58%) for small cell lung cancer (SCLC). The pooled mean platelet count for lung cancer patients was 289×109 /L (95% CI: 268 to 311). By subtype, this was 282×109 /L (95% CI: 259 to 306) for ADC, 297×109 /L (95% CI: 238 to 356) for SCC, 290×109 /L (95% CI: 176 to 404) for LCC, and 293×109 /L (95% CI: 244 to 342) for SCLC. There was no difference in thrombocytosis prevalence (p=0.76) or mean platelet count (p=0.96) across the subtypes.ConclusionWe report no evidence of differences in platelet levels across the major subtypes of lung cancer. A high platelet level is likely to be generic across all lung cancer subtypes.KEY MESSAGESWhat is the key question?Which (if any) subtype(s) of lung cancer are more associated with thrombocytosis?What is the bottom line?This can facilitate lung cancer diagnostics and provide insights into the biological mechanism between lung cancer and thrombocytosis.Why read on?This is the first systematic review to compare platelet count across different subtypes of lung cancer, combining data from 9,891 patients across 38 studies.
Clinical signs, symptoms, perceptions and impact on quality of life of patients suffering peri-implant diseases: a university-representative cross-sectional study
Authors: Romandini Mario , Lima Cristina , Pedrinaci Ignacio , Araoz Ana , Soldini Maria Costanza , Sanz Mariano 
Published: June 2020

AbstractAimTo study the symptoms and perception reported by patients with peri-implant diseases, as well as their signs and their potential impact on the oral health quality of life.Materials and Methods240 randomly selected patients were invited to participate. As part of the history assessment, the patient OHIP-14Sp was evaluated together with, for each implant, the patient perception regarding the peri-implant health status and the history of pain, spontaneous discomfort, bleeding, suppuration, swelling and discomfort during brushing. As part of the clinical examination, the following potential signs of peri-implant diseases were collected: probing pocket depth (PPD), mucosal dehiscence (MD), extent of BoP, presence of SoP, and visual signs of redness and swelling. Those parameters were analyzed in relation to the actual peri-implant health diagnosis.Results99 patients with a total of 458 dental implants were studied. Even in case of peri-implantitis, 88.89% of the implants were perceived by the patients as healthy. The total OHIP-14Sp sum score did not differ in relation to the peri-implant health diagnosis. Increased reports of spontaneous discomfort, bleeding, swelling and discomfort during brushing were observed in presence of disease. However, only a minor proportion of implants with peri-implant diseases presented symptoms. PPD≥6 mm was more frequent in diseased than in healthy implants(p<0.01), while PPD≥8 in pre-periimplantitis/peri-implantitis than in healthy/mucositis implants(p<0.01). Implants with peri-implantitis showed higher MD than implants without peri-implantitis(p<0.01).ConclusionsPeri-implant diseases are in most cases asymptomatic and not perceived by the patients. Despite being unable to accurately discriminate between peri-implant mucositis and peri-implantitis, PPD and MD resulted as the only two clinical signs associated with pre-periimplantitis/peri-implantitis.
Effectiveness of stay-in-place-orders during COVID-19 pandemic: Evidence from US border counties
Authors: Devaraj Srikant , Patel Pankaj C. 
Published: June 2020

AbstractRecent studies on US counties, with varying effect sizes, show that stay-in-place-orders (SIPOs) are associated with a decline in new COVID-19 cases. Our estimation approach relies on county-pairs across state-borders where one state has SIPO whereas the other state does not, controls for matched county-pair fixed effects and day of observation fixed-effects. The county-pair sample from southern, mid-western, and mountain region states (from March 1, 2020 to April 25, 2020) shows that daily COVID-19 incidence case growth rate is 1.994 percentage points lower for counties in SIPO states relative to those bordering in non-SIPO states. Specifically, we find SIPO reduced daily growth rates by 1.97, 2.14, 2.03, and 2.27 percentage points after 1 to 5 days, 6 to 10 days, 11 to 15 days, and 16 to 20 days, respectively. Our effect sizes are much smaller than in the previous studies with the caveat that states in the northeast and on the west coast could not be included in the border county-pair specification. We find limited evidence of heterogeneous effects in counties with a higher population density, percentage of black or Hispanic residents, proportion of population over 65 years, and social association rates in a county. Nor do we find evidence of meaningful differences in effects of SIPO by county Gini index, unemployment, or GDP. The results of this study could further inform policymakers in making decisions on SIPO extensions or lifting of such orders.JELH75; I18
An analysis of SARS-CoV-2 viral load by patient age
Authors: Jones Terry C. , Mühlemann Barbara , Veith Talitha , Biele Guido , Zuchowski Marta , Hofmann Jörg , Stein Angela , Edelmann Anke , Corman Victor Max , Drosten Christian 
Published: June 2020

AbstractAs children are under-represented in current studies aiming to analyse transmission of SARS-coronavirus 2 (SARS-CoV-2), their contribution to transmission is unclear. Viral load, as measured by RT-PCR, can inform considerations regarding transmission, especially if existing knowledge of viral load in other respiratory diseases is taken into account. RT-PCR threshold cycle data from 3303 patients who tested positive for SARS-CoV-2 (out of 77,996 persons tested in total, drawn from across Germany) were analysed to examine the relationship between patient age and estimated viral load. Two PCR systems were used. In data from the PCR system predominantly used for community and cluster screening during the early phase of the epidemic (Roche LightCycler 480 II), when such screening was frequent practice, viral loads do not differ significantly in three comparisons between young and old age groups (differences in log10 viral loads between young and old estimated from raw viral load data and a Bayesian mixture model of gamma distributions collectively range between −0.11 and −0.43). Data from a second type of PCR system (Roche cobas 6800/8800), introduced into diagnostic testing on March 16, 2020 and used during the time when household and other contact testing was reduced, show a credible but small difference in the three comparisons between young and old age groups (differences, measured as above, collectively range between −0.43 and −0.83). This small difference may be due to differential patterns of PCR instrument utilization rather than to an actual difference in viral load. Considering household transmission data on influenza, which has a similar viral load kinetic to SARS-CoV-2, the viral load differences between age groups observed in this study are likely to be of limited relevance. Combined data from both PCR instruments show that viral loads of at least 250,000 copies, a threshold we previously established for the isolation of infectious virus in cell culture at more than 5% probability, were present across the study period in 29.0% of kindergarten-aged patients 0-6 years old (n=38), 37.3% of those aged 0-19 (n=150), and in 51.4% of those aged 20 and above (n=3153). The differences in these fractions may also be due to differences in test utilization. We conclude that a considerable percentage of infected people in all age groups, including those who are pre- or mild-symptomatic, carry viral loads likely to represent infectivity. Based on these results and uncertainty about the remaining incidence, we recommend caution and careful monitoring during gradual lifting of non-pharmaceutical interventions. In particular, there is little evidence from the present study to support suggestions that children may not be as infectious as adults.