bluuebunny/crossref_metadata_2025_split huggingface dataset:
Auditory Profile-based Hearing-aid Fitting: A Proof-Of-Concept Study
Authors: Sanchez-Lopez Raul , Fereczkowski Michal , Santurette Sébastien , Dau Torsten , Neher Tobias 
Published: April 2020

AbstractObjectiveThe clinical characterization of hearing deficits for hearing-aid fitting purposes is typically based on the pure-tone audiogram only. In a previous study, a group of hearing-impaired listeners were tested using a comprehensive test battery designed to tap into different aspects of hearing. A data-driven analysis of the data yielded four clinically relevant patient subpopulations or “auditory profiles”. In the current study, profile-based hearing-aid settings were proposed and evaluated to explore their potential for providing more targeted hearing-aid treatment.DesignFour candidate hearing-aid settings were implemented and evaluated by a subset of the participants tested previously. The evaluation consisted of multi-comparison preference ratings carried out in realistic sound scenarios.ResultsListeners belonging to the different auditory profiles showed different patterns of preference for the tested hearing-aid settings that were largely consistent with the expectations.ConclusionThe results of this proof-of-concept study support further investigations into stratified, profile-based hearing-aid fitting with wearable hearing aids.
Open Development and Clinical Validation Of Multiple 3D-Printed Sample-Collection Swabs: Rapid Resolution of a Critical COVID-19 Testing Bottleneck
Authors: Callahan Cody J , Lee Rose , Zulauf Katelyn E. , Tamburello Lauren , Smith Kenneth P. , Previtera Joe , Cheng Annie , Green Alex , Azim Ahmed Abdul , Yano Amanda , Doraiswami Nancy , Kirby James E. , Arnaout Ramy A. 
Published: April 2020

AbstractThe SARS-CoV-2 pandemic has caused a severe international shortage of the nasopharyngeal swabs that are required for collection of optimal specimens, creating a critical bottleneck in the way of high-sensitivity virological testing for COVID-19. To address this crisis, we designed and executed an innovative, radically cooperative, rapid-response translational-research program that brought together healthcare workers, manufacturers, and scientists to emergently develop and clinically validate new swabs for immediate mass production by 3D printing. We performed a rigorous multi-step preclinical evaluation on 160 swab designs and 48 materials from 24 companies, laboratories, and individuals, and shared results and other feedback via a public data repository (http://github.com/rarnaout/Covidswab/). We validated four prototypes through an institutional review board (IRB)-approved clinical trial that involved 276 outpatient volunteers who presented to our hospital’s drive-through testing center with symptoms suspicious for COVID-19. Each participant was swabbed with a reference swab (the control) and a prototype, and SARS-CoV-2 reverse-transcriptase polymerase chain reaction (RT-PCR) results were compared. All prototypes displayed excellent concordance with the control (κ=0.85-0.89). Cycle-threshold (Ct) values were not significantly different between each prototype and the control, supporting the new swabs’ non-inferiority (Mann-Whitney U [MWU] p>0.05). Study staff preferred one of the prototypes over the others and the control swab overall. The total time elapsed between identification of the problem and validation of the first prototype was 22 days. Contact information for ordering can be found at http://printedswabs.org. Our experience holds lessons for the rapid development, validation, and deployment of new technology for this pandemic and beyond.
Optimal Allocation of COVID-19 Test Kits Among Accredited Testing Centers in the Philippines
Authors: Buhat Christian Alvin H. , Duero Jessa Camille C. , Felix Edd Francis O. , Rabajante Jomar F. , Mamplata Jonathan B. 
Published: April 2020

AbstractTesting is crucial for early detection, isolation, and treatment of coronavirus disease (COVID-19)-infected individuals. However, in resource-constrained countries such as the Philippines, test kits have limited availability. As of 12 April 2020, there are 11 testing centers in the country that have been accredited by the Department of Health (DOH) to conduct testing. In this paper, we determine the optimal percentage allocation of COVID-19 test kits among accredited testing centers in the Philippines that gives an equitable chance to all infected individuals to be tested. Heterogeneity in testing accessibility, population density of municipalities, and the capacity of testing facilities are included in the model. Our results showed that the range of optimal allocation per testing center are: Research Institute for Tropical Medicine (4.17% −6.34%), San Lazaro Hospital (14.65% −24.03%), University of the Philippines-National Institutes of Health (16.25% −44.80%), Lung Center of the Philippines (15.8% −26.40%), Baguio General Hospital Medical Center (0.58% −0.76%), The Medical City, Pasig City (5.96% −25.51%), St. Luke’s Medical Center, Quezon City (1.09% −6.70%), Bicol Public Health Laboratory (0.06% −0.08%), Western Visayas Medical Center (0.71% −4.52%), Vicente Sotto Memorial Medical Center (1.02% −2.61%), and Southern Philippines Medical Center (≈0.01%). If there will be changes in the number of testing centers, our model can still be used to modify the test kit allocation. Our results can serve as a guide to the authorities in distributing the COVID-19 test kits. These can also be used to determine the capacity of testing centers and the effects of increasing its number. The model can also be used for proposing additional number and location of new testing centers.
Model calibration, nowcasting, and operational prediction of the COVID-19 pandemic
Authors: Annan J. D. , Hargreaves J. C. 
Published: April 2020

AbstractWe present a simple operational nowcasting/forecasting scheme based on a joint state/parameter estimate of the COVID-19 epidemic at national or regional scale, performed by assimilating the time series of reported daily death numbers into a simple SEIR model. This system generates estimates of the current reproductive rate, Rt, together with predictions of future daily deaths and clearly outperforms a number of alternative forecasting systems that have been presented recently. Our current (14th April 2020) estimates for Rt are, respectively, UK 0.49 (0.0 – 1.02), Spain 0.55 (0.33 – 0.77), Italy 0.90 (0.74 – 1.06) and France 0.67 (0.40 – 0.94) (mean and 95% credible intervals). Thus, we believe that the epidemics have been successfully suppressed in each of these countries, with high probability. Our approach is trivial to set up for any region and generates results in a few minutes on a laptop. We believe it would be straightforward to set up equivalent frameworks using more complex and realistic models, and hope that some experts in the field of epidemiological modelling will consider investigating this approach further.
Redox imbalance and oxidative DNA damage during isoniazid treatment: A clinical and translational pharmacokinetic study
Authors: Zentner Isaac , Back Hyun-moon , Kagan Leonid , Subbian Selvakumar , Nagajyothi Jyothi , Srivastava Shashikant , Pasipanodya Jotam , Gumbo Tawanda , Bisson Gregory P. , Vinnard Christopher 
Published: April 2020

ABSTRACTBackgroundThe potential for hepatotoxicity during isoniazid-based tuberculosis (TB) treatment presents a major challenge for TB control programs worldwide. We sought to determine whether pharmacokinetic exposures of isoniazid and its metabolites were related to cellular oxidation/reduction status and downstream markers of oxidative DNA damage.MethodsWe performed intensive pharmacokinetic sampling among isoniazid-treated patients to determine the relative plasma exposures of isoniazid, acetylisoniazid, hydrazine, and acetylhydrazine. Physiologically-based pharmacokinetic modeling was used to estimate liver tissue exposures during a 24-hour dosing interval for each compound. We experimentally treated HepG2 cells with isoniazid and metabolites at equimolar concentrations corresponding to these exposures for 7, 14, and 28 day periods, and performed assays related to redox imbalance and oxidative DNA damage at each timepoint. We related a urine marker of oxidative DNA damage to serum isoniazid pharmacokinetic exposures and pharmacogenetics in a clinical study.ResultsAmong isoniazid-treated patients, serum concentrations of hydrazine and isoniazid concentrations were highly correlated. At equimolar concentrations that approximated hepatic tissue exposures during a 24-hour dosing interval, hydrazine demonstrated the highest levels of redox imbalance, mitochondrial injury, and oxidative DNA damage over a 28-day treatment period. In a clinical validation study of isoniazid-treated TB patients, peak isoniazid serum concentrations were positively associated with a urine biomarker of oxidative DNA damage.ConclusionsIsoniazid and its metabolites share the potential for oxidative cellular damage, with the greatest effects observed for hydrazine. Future studies should investigate the clinical consequences of oxidative stress with regards to clinical episodes of drug induced liver injury during isoniazid treatment.
Application of Telemedicine During the Coronavirus Disease Epidemics: A Rapid Review and Meta-Analysis
Authors: Gao Yelei , Liu Rui , Zhou Qi , Wang Xingmei , Huang Liping , Shi Qianling , Wang Zijun , Lu Shuya , Li Weiguo , Ma Yanfang , Luo Xufei , Fukuoka Toshio , Ahn Hyeong Sik , Lee Myeong Soo , Luo Zhengxiu , Liu Enmei , Chen Yaolong , Shu Chang , Tian Daiying 
Published: April 2020

AbstractBackgroundAs COVID-19 has become a global pandemic, early prevention and control of the epidemic is extremely important. Telemedicine, which includes medical advice given over telephone, Internet, mobile phone applications or other similar ways, may be an efficient way to reduce transmission and pressure on medical institutions.MethodsWe searched MEDLINE, Web of science, Embase, Cochrane, CBM, CNKI and Wanfang databases for literature on the use of telemedicine for COVID-19, SARS and MERS. from their inception to March 31st, 2020. We included studies about the content of the consultation (such as symptoms, therapy and prevention, policy, public service), screening of suspected cases, the provision of advice given to those people who may have symptoms or contact history. We conducted meta-analyses on the main outcomes of the studies.ResultsA total of 2041 articles were identified after removing duplicates. After reading the full texts, we finally included nine studies. People were most concerned about symptoms (64.2%), epidemic situation and public problems (14.5%), and psychological problems (10.3%) during COVID-19 epidemic. During the SARS epidemic, the proportions of people asking for consultation for symptoms, prevention and therapy, and psychological problems were 35.0%, 22.0%, and 23.0%, respectively. Two studies demonstrated that telemedicine can be used to screen the suspected patients and give advice. One study emphasized the limited possibilities to follow up people calling hotlines and difficulties in identifying all suspect cases.ConclusionsTelemedicine services should focus on the issues that the public is most concerned about, such as then symptoms, prevention and treatment of the disease, and provide reasonable advice to patients with symptoms or people with epidemic history.
Association of inflammatory markers with the severity of COVID-19
Authors: Zeng Furong , Guo Ying , Yin Mingzhu , Chen Xiang , Deng Guangtong 
Published: April 2020

AbstractBackgroundThe ongoing worldwide epidemic of Coronavirus Disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV- 2), has posed a huge threat to global public health. However, with regard to the effects of inflammatory markers on the severity of COVID-19, studies have reported associations that vary in strength and direction.AimsIn the meta-analysis, we aimed to provide an overview of the association of inflammatory markers with severity of COVID-19.MethodsThe following databases were searched: PubMed, Embase, Cochrane Library, Wanfang database and CNKI (China National Knowledge Infrastructure) database until March 20, 2020. Weighted mean difference (WMD) and 95% confidence intervals (CIs) were pooled using random or fixed-effects models.ResultsA total of 16 studies were included in our analysis comprising of 3962 patients with COVID-19. Random-effects results demonstrated that patients with COVID-19 in non-severe group had lower levels for CRP (WMD = -41.78 mg/l, 95% CI = [-52.43, - 31.13], P < 0.001), PCT (WMD = -0.13 ng/ml, 95% CI = [-0.20, -0.05], P < 0.001), IL- 6 (WMD = -21.32 ng/l, 95% CI = [-28.34, -14.31], P < 0.001), ESR (WMD = - 8.40 mm/h, 95% CI = [-14.32, -2.48], P = 0.005), SAA (WMD = -43.35 μg/ml, 95% CI = [-80.85, -5.85], P = 0.020) and serum ferritin (WMD = -398.80 mg/l, 95% CI = [- 625.89, -171.71], P < 0.001), compared with those in severe group. Moreover, survivors had lower level for IL-6 than non-survivors with COVID-19 (WMD = -4.80 ng/ml, 95% CI = [-5.87, -3.73], P < 0.001). These results were consistent through sensitivity analysis and publication bias assessment.ConclusionsThe meta-analysis highlights the association of inflammatory markers with the severity of COVID-19. Measurement of inflammatory markers might help clinicians to monitor and evaluate the severity and prognosis of COVID-19.
Nature of transmission of Covid19 in India
Authors: Roy Anushree , Kar Sayan 
Published: April 2020

AbstractWe examine available data on the number of individuals infected by the Covid-19 virus, across several different states in India, over the period January 30, 2020 to April 10, 2020. It is found that the growth of the number of infected individuals N(t) can be modeled across different states with a simple linear function N(t) = γ + αt beyond the date when reasonable number of individuals were tested (and when a countrywide lockdown was imposed). The slope α is different for different states. Following recent work by Notari (arxiv:2003.12417), we then consider the dependency of the α for different states on the average maximum and minimum temperatures, the average relative humidity and the population density in each state. It turns out that like other countries, the parameter α, which determines the rate of rise of the number of infected individuals, seems to have a weak correlation with the average maximum temperature of the state. In contrast, any significant variation of α with humidity or minimum temperature seems absent with almost no meaningful correlation. Expectedly, α increases (slightly) with increase in the population density of the states; however, the degree of correlation here too is negligible. These results seem to barely suggest that a natural cause like a hot summer (larger maximum temperatures) may contribute towards reducing the transmission of the virus, though the role of minimum temperature, humidity and population density remains somewhat obscure from the inferences which may be drawn from presently available data.
Microbial-induced calcium carbonate precipitation: An experimental toolbox for in situ and real-time investigation of micro-scale pH evolution
Authors: Zehner Jennifer , Røyne Anja , Wentzel Alexander , Sikorski Pawel 
Published: April 2020

AbstractConcrete is the second most consumed product by humans, after water. However, the production of cement, which is used as a binding material in concrete, causes more than 5% of anthropogenic CO2emissions and has therefore a significant contribution to climate change and global warming. Due to increasing environmental awareness and international climate goals, there is a need for emission-reduced materials, that can replace conventional concrete in certain applications. One path to produce a solid, concrete-like construction material is microbial-induced calcium carbonate precipitation (MICP). As a calcium source in MICP, crushed limestone, which mainly consists out of CaCO3, can be dissolved with acids, for example lactic acid. The pH evolution during crystallization and dissolution processes provides important information about kinetics of the reactions. However, previous research on MICP has mainly been focused on macro-scale pH evolution and on characterization of the finished material. To get a better understanding of MICP it is important to be able to follow also local pH changes in a sample. In this work we present a new method to study processes of MICP at micro-scalein situand in real time. We present two different methods to monitor the pH changes during the precipitation process of CaCO3. In the first method, the average pHs of small sample volumes are measured in real time, and pH changes are subsequently correlated with processes in the sample by comparing to optical microscope results. The second method is introduced to follow local pH changes at a grain scale insituand in real time. Furthermore, local pH changes during the dissolution of CaCO3crystals are monitored. We demonstrate that these two methods are powerful tools to investigate pH changes for both MICP precipitation and CaCO3dissolution for knowledge-based improvement of MICP-based material properties.Graphical TOC Entry
Optimizing RT-PCR detection of SARS-CoV-2 for developing countries using pool testing
Authors: Farfan Mauricio J. , Torres Juan P. , O’Ryan Miguel , Olivares Mauricio , Gallardo Pablo , Salas Carolina 
Published: April 2020

AbstractThe global shortage of reagents and kits for nucleic acid extraction and molecular detection of SARS-CoV-2, requires new cost-effective strategies for the diagnosis of suspected COVID-19 cases, especially in countries that need to increase detection capacity. Pooled nucleic acid testing has been extensively used as a cost-effective strategy for HIV, HepB, HepC and influenza. Also, protocols dispensing of RNA extraction appears as an attractive option for detection of SARS-CoV-2. In this study, pooling nasopharyngeal samples with both automated and manual extraction proved reliable, and thus a potential efficient alternative for the diagnosis of suspected COVID-19 in developing countries.
A region of Drosophila SLBP distinct from the histone pre-mRNA binding and processing domains is essential for deposition of histone mRNA in the oocyte
Authors: Potter-Birriel Jennifer , Gonsalvez Graydon B. , Marzluff William F. 
Published: April 2020

ABSTRACTDuringDrosophilaoogenesis, large amounts of histone mRNA and proteins are deposited in the developing oocyte. These are sufficient for the first 14 embryonic cell cycles and provide the developing embryo with sufficient histone proteins until the zygotic histone genes are activated. The maternally deposited histone mRNA is synthesized in stage 10b of oogenesis after completion of endoreduplication of the nurse cells. Histone mRNAs are the only cellular mRNAs that are not polyadenylated, ending instead in a conserved stemloop instead of a polyA tail. The Stem-loop binding protein (SLBP) binds the 3’ end of histone mRNA and is essential for both the biosynthesis and translation of histone mRNA. We report that a 10 aa region in SLBP, which is not required for processing in vitro, is essential for transcription of histone mRNA in the stage 10b oocyte. In stage 10b the Histone Locus Bodies (HLBs) produce histone mRNAs in the absence of phosphorylation of Mxc, normally required for histone gene expression in S-phase cells. Mutants expressing this SLBP develop normally, produce small amounts of polyadenylated histone mRNA throughout development, but little histone mRNA in stage 10b resulting in death of the embryos in the first hr of development.
Omics-Based Interaction Framework – a systems model to reveal molecular drivers of synergy
Authors: García Jezreel Pantaleón , Kulkarni Vikram V. , Reese Tanner C. , Wali Shradha , Wase Saima J. , Zhang Jiexin , Singh Ratnakar , Caetano Mauricio S. , Moghaddam Seyed Javad , Johnson Faye M. , Wang Jing , Wang Yongxing , Evans Scott E. 
Published: April 2020

AbstractBioactive molecule library screening strategies may empirically identify effective combination therapies. However, without a systems theory to interrogate synergistic responses, the molecular mechanisms underlying favorable drug-drug interactions remain unclear, precluding rational design of combination therapies. Here, we introduce Omics-Based Interaction Framework (OBIF) to reveal molecular drivers of synergy through integration of statistical and biological interactions in supra-additive biological responses. OBIF performs full factorial analysis of feature expression data from single vs. dual factor exposures to identify molecular clusters that reveal synergy-mediating pathways, functions and regulators. As a practical demonstration, OBIF analyzed a therapeutic dyad of immunostimulatory small molecules that induces synergistic protection against influenza A pneumonia. OBIF analysis of transcriptomic and proteomic data identified biologically relevant, unanticipated cooperation between RelA and cJun that we subsequently confirmed to be required for the synergistic antiviral protection. To demonstrate generalizability, OBIF was applied to data from a diverse array of Omics platforms and experimental conditions, successfully identifying the molecular clusters driving their synergistic responses. Hence, OBIF is a phenotype-driven systems model that supports multiplatform exploration of synergy mechanisms.
Evolutionary divergence of potential drought adaptations between two subspecies of an annual plant: Do some constraints need to be broken?
Authors: Burnette Timothy E. , Eckhart Vincent M. 
Published: April 2020

PremiseWhether mechanisms of drought adaptation tend to evolve together, evolve independently, and/or evolve constrained by genetic architecture is incompletely resolved, particularly for water-relations traits besides gas exchange. We addressed this question in two subspecies ofClarkia xantiana(Onagraceae), California winter annuals that diverged approximately 65,000 years ago and that are adapted, partly by differences in flowering time, to native ranges that differ in precipitation.MethodsIn these subspecies and in F5recombinant inbred lines (RILs) from a cross between them we scored drought-adaptation traits related to phenology (times to seed germination and to flowering) and tissue water relations (measures of succulence; pressure-volume curve parameters), in common environments.ResultsSubspecies differed distinctly. The one native to more arid environments had some trait values associated with drought adaptation (e.g., early flowering and high succulence) but had higher osmotic potential at full turgor and lost turgor at higher water potential, indicating poorer tolerance of dehydration. Traits that differed between subspecies exhibited substantial genetic variation, with broad-sense heritability from 0.09 (stem succulence) to 0.43 (time to flowering). The genetic correlation structure suggests facilitated evolution of some trait combinations that might enhance drought adaptation (e.g., high succulence plus low turgor loss point), but the subspecies exhibit some trait combinations that do not follow genetic correlations.ConclusionsAs lineages diverged in their potential to escape drought by early flowering, other traits diverged as well. Genetic architecture might facilitate some correlated evolutionary responses to drought, but particular trait combinations also can evolve despite apparent genetic constraints.