bluuebunny/crossref_metadata_2025_split huggingface dataset:
Religion and Spirituality, Meaning, and Faith in American Psychiatry From the 19th to the 21st Century
Authors: Hirshbein Laura 
Published: July 2020

Abstract
Since the beginning of American psychiatry, we have discovered and rediscovered connections among religion, spirituality, meaning, and mental health. In the 19th century, religion was an embedded attribute of moral therapy, the framework for treatment in mental institutions. During the decades in the 20th century when psychoanalysis was ascendant in the profession, some psychiatrists collaborated with the emerging field of pastoral care. As biological psychiatry has come to dominate the profession, though, pastoral care providers and some psychiatric researchers have identified gaps in the human interactions that characterize ideal and meaningful encounters with patients. This article examines how religion has been mobilized in American psychiatry over the centuries within institutional settings, but also looks at a broad consideration of faith in psychiatrists' clinical interventions, how that has affected their interactions with religious ideas and people, and where they have found meaning and purpose in mental health care.
Identifying economically viable tidal sites within the Alderney Race through optimization of levelized cost of energy
Authors: Goss Z. L. , Coles D. S. , Piggott M. D. 
Published: July 2020

Costs of tidal stream energy generation are anticipated to fall considerably with array expansion and time. This is due to both economies of volume, where arrays comprising of large numbers of turbines can split fixed costs over a greater number of devices, and learning rates, where the industry matures and so arrays of the same size become cheaper due to lessons learned from previous installations. This paper investigates how tidal energy arrays can be designed to minimize the levelized cost of energy (LCOE), by optimizing not only the location but also the number of devices, to find a suitable balance between decreased costs due to economies of volume and diminishing returns due to global blockage effects. It focuses on the Alderney Race as a case study site due to the high velocities found there, making it a highly suitable site for large-scale arrays. It is demonstrated that between 1 and 2 GW could be feasibly extracted as costs in the tidal industry fall, with the LCOE depending greatly on the assumed costs. A Monte–Carlo analysis is undertaken to account for variability in capital and operational cost data used as inputs to the array optimization. Once optimized, the estimated P50 LCOE of an 80 MW array is £110/MWh. This estimate aligns closely with the level of subsidy considered for tidal stream projects in the Alderney Race in the past.
This article is part of the theme issue ‘New insights on tidal dynamics and tidal energy harvesting in the Alderney Race’.
Population Data-Driven Formulation of a COVID-19 Therapeutic
Authors: Campbell Heather R. , Cecil Regan , Lodder Robert A. 
Published: July 2020

AbstractThis study is designed to utilize computer modeling of the US population through NHANES to reduce the need for preclinical formulation and toxicology studies of an Ebola anti-viral (BSN389) being repurposed for COVID-19, and to thereby speed the candidate therapeutic to the clinic.
COVID-19 Patients Form Memory CD8+ T Cells that Recognize a Small Set of Shared Immunodominant Epitopes in SARS-CoV-2
Authors: Ferretti Andrew P. , Kula Tomasz , Wang Yifan , Nguyen Dalena M.V. , Weinheimer Adam , Dunlap Garrett S. , Xu Qikai , Nabilsi Nancy , Perullo Candace R. , Cristofaro Alexander W. , Whitton Holly J. , Virbasius Amy , Olivier Kenneth J. , Baiamonte Lyndsey B. , Alistar Angela T. , Whitman Eric D. , Bertino Sarah A. , Chattopadhyay Shrikanta , MacBeath Gavin 
Published: July 2020

AbstractDevelopment of effective strategies to detect, treat, or prevent COVID-19 requires a robust understanding of the natural immune response to SARS-CoV-2, including the cellular response mediated by T cells. We used an unbiased, genome-wide screening technology, termed T-Scan, to identify specific epitopes in SARS-CoV-2 that are recognized by the memory CD8+ T cells of 25 COVID-19 convalescent patients, focusing on epitopes presented by the six most prevalent HLA types: A*02:01, A*01:01, A*03:01, A*11:01, A*24:02, and B*07:02. For each HLA type, the patients’ T cells recognized 3–8 immunodominant epitopes that are broadly shared among patients. Remarkably, 94% of screened patients had T cells that recognized at least one of the three most dominant epitopes for a given HLA, and 53% of patients had T cells that recognized all three. Subsequent validation studies in 18 additional A*02:01 patients confirmed the presence of memory CD8+ T cells specific for the top six A*02:01 epitopes, and single-cell sequencing revealed that patients often have many different T cell clones targeting each epitope, but that the same T cell receptor Vα regions are predominantly used to recognize these epitopes, even across patients. In total, we identified 29 shared epitopes across the six HLA types studied. T cells that target most of these epitopes (27 of 29) do not cross-react with the endemic coronaviruses that cause the common cold, and the epitopes do not occur in regions with high mutational variation. Notably, only 3 of the 29 epitopes reside in the spike protein, highlighting the need to design new classes of vaccines that recapitulate natural CD8+ T cell responses to SARS-CoV-2.
SEIHCRD Model for COVID-19 spread scenarios, disease predictions and estimates the basic reproduction number, case fatality rate, hospital, and ICU beds requirement
Authors: Singh Avaneesh , Bajpai Manish Kumar 
Published: July 2020

AbstractWe have proposed a new mathematical method, SEIHCRD-Model that is an extension of the SEIR-Model adding hospitalized and critical two-compartments. SEIHCRD model has seven compartments: susceptible (S), exposed (E), infected (I), hospitalized (H), critical (C), recovered (R), and deceased or death (D), collectively termed SEIHCRD. We have studied COVID-19 cases of six countries, where the impact of this disease in the highest are Brazil, India, Italy, Spain, the United Kingdom, and the United States. SEIHCRD model is estimating COVID-19 spread and forecasting under uncertainties, constrained by various observed data in the present manuscript. We have first collected the data for a specific period, then fit the model for death cases, got the values of some parameters from it, and then estimate the basic reproduction number over time, which is nearly equal to real data, infection rate, and recovery rate of COVID-19. We also compute the case fatality rate over time of COVID-19 most affected countries. SEIHCRD model computes two types of Case fatality rate one is CFR daily and the second one is total CFR. We analyze the spread and endpoint of COVID-19 based on these estimates. SEIHCRD model is time-dependent hence we estimate the date and magnitude of peaks of corresponding to the number of exposed cases, infected cases, hospitalized cases, critical cases, and the number of deceased cases of COVID-19 over time. SEIHCRD model has incorporated the social distancing parameter, different age groups analysis, number of ICU beds, number of hospital beds, and estimation of how much hospital beds and ICU beds are required in near future.
Effects of individual base-pairs onin vivotarget search and destruction kinetics of small RNA
Authors: Poddar Anustup , Azam Muhammad S. , Kayikcioglu Tunc , Bobrovskyy Maksym , Zhang Jichuan , Ma Xiangqian , Labhsetwar Piyush , Fei Jingyi , Singh Digvijay , Luthey-Schulten Zaida , Vanderpool Carin K. , Ha Taekjip 
Published: July 2020

AbstractBase-pairing interactions mediate intermolecular target recognition in many biological systems and applications, including DNA repair, CRISPR, microRNA, small RNA (sRNA) and antisense oligo therapies. Even a single base-pair mismatch can cause a substantial difference in biological activity but presently we do not yet know how the target search kineticsin vivoare influenced by single nucleotide level changes. Here, we used high-throughput sequencing to identify functionally relevant single point mutants of the bacterial sRNA, SgrS, and quantitative super-resolution microscopy to probe the mutational impact on the regulation of its primary target,ptsGmRNA. Our super-resolution imaging and analysis platform allowed us to further dissect mutational effects on SgrS lifetimes, and even subtle changes in thein vivorates of target association,kon, and dissociation,koff. Mutations that disrupt binding of a chaperone protein, Hfq, and are distal to the mRNA annealing region still decreasedkonand increasedkoff, providing anin vivodemonstration that Hfq directly facilitates sRNA-mRNA annealing. Single base-pair mismatches in the annealing region reducedkonby 24-31% and increasedkoffby 14-25%, extending the time it takes to find and destroy the target mRNA by about a third, depending on whether an AU or GC base-pair is disrupted. The effects of disrupting contiguous base-pairing are much more modest than that expected from thermodynamics, suggesting that Hfq also buffers base-pair disruptions.
Inference of a genome-wide protein-coding gene set of the inshore hagfishEptatretus burgeri
Authors: Yamaguchi Kazuaki , Hara Yuichiro , Tatsumi Kaori , Nishimura Osamu , Smith Jeramiah J. , Kadota Mitsutaka , Kuraku Shigehiro 
Published: July 2020

AbstractThe group of hagfishes (Myxiniformes) arose from agnathan (jawless vertebrate) lineages and is one of the only two extant cyclostome taxa, together with lampreys (Petromyzontiformes). Even though whole genome sequencing has been achieved for diverse vertebrate taxa, genome-wide sequence information has been highly limited for cyclostomes. Here we sequenced the genome of the inshore hagfishEptatretus burgeriusing DNA extracted from the testis, with a short-read sequencing platform, aiming at reconstructing a high-coverage coding gene catalogue. The obtained genome assembly, scaffolded with mate-pair reads and paired RNA-seq reads, exhibited an N50 scaffold length of 293 Kbp, which allowed the genome-wide prediction of coding genes. This computation resulted in the gene models whose completeness was estimated at the complete coverage of more than 83 % and the partial coverage of more than 93 % by referring to evolutionarily conserved single-copy orthologs. The high contiguity of the assembly and completeness of resulting gene models promises a high utility in various comparative analyses including phylogenomics and phylome exploration.
Loss of resistance to punishment of cocaine use after prior experience
Authors: Durand Audrey , Girardeau Paul , Freese Luana , Ahmed Serge H. 
Published: July 2020

ABSTRACTOne behavioral feature of drug addiction is continued drug use despite awareness that this causes negative consequences. Attempts to model this feature in animals typically involve punishing drug self-administration with a brief electrical footshock and look for resistance to punishment. Though all individual animals eventually stop self-administering the drug with increasing intensity of punishment, some individuals do so at higher intensities than other individuals. The greater relative resistance to punishment of the former individuals is generally interpreted as evidence for a compulsion-like behavior. Here we show that resistance to footshock punishment is in fact not a stable individual behavioral feature. Specifically, when rats are retested for their resistance to increasing intensity of footshock punishment, they become much less resistant. As a result, they suppress their cocaine intake even when punished with an initially low and ineffective intensity. A series of original behavioral experiments reveals that this low resistance to footshock punishment is rapidly acquired after rats experience a punishment intensity that leads them to near-completely suppress their cocaine intake. Passive exposure to the same intensity does not induce this effect. Once acquired, low resistance to punishment persists during at least one month, but can nevertheless be extinguished by retesting rats on a daily basis. Interestingly, this acquired low resistance to footshock punishment does not generalize to a non-painful form of punishment (i.e., histamine) that is also seldom used in animal drug self-administration studies. We discuss some possible theoretical and methodological implications of these findings for future research on animal models of compulsion-like behavior.
Triplanar ensemble U-Net model for white matter hyperintensities segmentation on MR images
Authors: Sundaresan Vaanathi , Zamboni Giovanna , Rothwell Peter M. , Jenkinson Mark , Griffanti Ludovica 
Published: July 2020

AbstractWhite matter hyperintensities (WMHs) have been associated with various cerebrovascular and neurodegenerative diseases. Reliable quantification of WMHs is essential for understanding their clinical impact in normal and pathological populations. Automated segmentation of WMHs is highly challenging due to heterogeneity in WMH characteristics between deep and periventricular white matter, presence of artefacts and differences in the pathology and demographics of populations. In this work, we propose an ensemble triplanar network that combines the predictions from three different planes of brain MR images to provide an accurate WMH segmentation. Also, the network uses anatomical information regarding WMH spatial distribution in loss functions for improving the efficiency of segmentation and to overcome the contrast variations between deep and periventricular WMHs. We evaluated our method on 5 datasets, of which 3 are part of a publicly available dataset (training data for MICCAI WMH Segmentation Challenge 2017 - MWSC 2017) consisting of subjects from three different cohorts. On evaluating our method separately in deep and periventricular regions, we observed robust and comparable performance in both regions. Our method performed better than most of the existing methods, including FSL BIANCA, and on par with the top ranking deep learning method of MWSC 2017.
Temperature Dependence of theKrokinobacterrhodopsin 2 Kinetics
Authors: Eberhardt P. , Slavov C. , Sörmann J. , Bamann C. , Braun M. , Wachtveitl J. 
Published: July 2020

ABSTRACTHere we applied target analysis to a temperature dependent flash photolysis dataset of the light-driven sodium ion pumpKrokinobacterrhodopsin 2 (KR2) at sodium pumping conditions. With an increase in temperature from 10 – 40 °C, the overall photocycle duration was accelerated by a factor of six, while single transitions like the L to M transition increased by a factor of 40. Using kinetic modeling with the Eyring constraint as well as spectral corrections on the datasets the spectral position as well as the equilibria of the different photointermediates could be resolved. The results provide further insight into KR2s photocycle and energetics.STATEMENT OF SIGNIFICANCEKR2 is the most prominent member of the new class of non-proton cation pumps, as it represents an interesting new optogenetic tool. Despite widespread biophysical investigations, the molecular mechanisms of light-induced sodium pumping in KR2 are still not sufficiently understood. Therefore, an expanded set of thermodynamic parameters is essential for a complete picture. Our study of the KR2 photocycle shows that different steps in the photocycle are affected differently by temperature changes. Rigorous data analysis provides strong evidence that the transient states observed in time-resolved experiments represent rather equilibria between the different photocycle intermediates than pure intermediates. Gaining access to the dynamics and energetics of KR2 helps to answer long standing open questions concerning the molecular mechanism of cation pumping.
Specific changes in sleep oscillations after blocking human metabotropic glutamate receptor 5 in the absence of altered memory function
Authors: Feld Gordon B. , Bergmann Til Ole , Alizadeh-Asfestani Marjan , Stuke Viola , Wriede Jan-Philipp , Soekadar Surjo , Born Jan 
Published: July 2020

AbstractBackgroundSleep consolidates declarative memory by repeated replay linked to the cardinal oscillations of NonREM sleep. However, there is so far little evidence of classical glutamatergic plasticity induced by this replay. Rather, we have previously reported that blocking NMDA or AMPA receptors does not affect sleep-dependent consolidation of declarative memory.AimsInvestigate the role of metabotropic glutamate receptor 5 (mGluR5) on memory processing during sleep.MethodsIn two placebo-controlled within-subject cross-over experiments with 20 healthy humans each, we used fenobam to block mGluR5 during sleep. In Experiment I, participants learned word-pairs (declarative task) and a finger sequence (procedural task) in the evening, then received the drug and recall was tested in the next morning. To cover possible effects on synaptic renormalization processes during sleep, in Experiment II, participants learned new word-pairs in the morning after sleep.Results/OutcomesSurprisingly, fenobam neither reduced retention of memory across sleep nor new learning after sleep, although it severely altered sleep architecture and memoryrelevant EEG oscillations. In NonREM sleep, fenobam suppressed 12-15 Hz spindles but augmented 2-4 Hz delta waves, whereas in REM sleep it suppressed 4-8 Hz theta and 16-22 Hz beta waves. Notably, under Fenobam NonREM spindles became more consistently phase-coupled to the slow oscillation.Conclusions/InterpretationsOur findings indicate that mGluR5-related plasticity is not essential for memory processing during sleep, even though mGlurR5 are strongly implicated in the regulation of the cardinal sleep oscillations.Declaration of interest/FundingThe authors have nothing to disclose and funders had no influence on the research presented here.
A simple strategy to reduce the salivary gland and kidney uptake of PSMA targeting small molecule radiopharmaceuticals
Authors: Kalidindi Teja Muralidhar , Lee Sang-Gyu , Jou Katerina , Chakraborty Goutam , Skafida Myrto , Tagawa Scott T. , Bander Neil H. , Schoder Heiko , Bodei Lisa , Pandit-Taskar Neeta , Lewis Jason S. , Larson Steven M. , Osborne Joseph R. , Kishore Pillarsetty Naga Vara 
Published: July 2020

AbstractThe past five years have seen an increasing acceptance of peptide-based prostate-specific membrane antigen (PSMA)-targeted radionuclide therapy (TRT) agents for treatment of metastatic castration-resistant prostate cancer (mCRPC), with [177Lu]-DKFZ-PSMA-617 ([177Lu]-PSMA-617) emerging as the leading candidate. [177Lu]-PSMA-617 and other PSMA ligands have shown efficacy in reducing the tumor burden in mCRPC patients but irradiation to salivary gland and kidneys is a concern and dose limiting factor. Therefore, methods to reduce non-target organ toxicity are needed to safely treat patients and preserve their quality of life. Here, we report the effects of the addition of the cold PSMA ligand DKFZ-PSMA-11 (PSMA-11) on the uptake of [177Lu]-PSMA-617 in tumor, salivary glands and kidneys. Groups of athymic nude mice (n = 4) bearing PC3-PIP (PSMA+) tumor xenografts were administered with [177Lu]-PSMA-617 along with 0, 5, 100, 500, 1000 and 2000 pmoles of PSMA-11. Biodistribution studies 1 h post-administration revealed that [177Lu]-PSMA-617 uptake in PSMA-expressing PC3-PIP tumors was 21.71±6.13, 18.7±2.03, 26.44±2.94, 16.21±3.5, 13.52±3.68, and 12.03±1.96 %ID/g when 0, 5, 100, 500, 1000 and 2000 pmoles of PSMA-11 were added, respectively. Corresponding kidney uptake values were 123.14±52.52, 132.31±47.4, 84.29±78.25, 2.12±1.88, 1.16±0.36, 0.64±0.23 %ID/g, respectively. Corresponding salivary gland uptake values were 0.48±0.11, 0.45±0.15, 0.38±0.3, 0.08±0.03, 0.09±0.07, 0.05±0.02 % ID/g, respectively. Thus, uptake of PSMA TRT agents in salivary gland and kidney can be substantially reduced without impact on tumor uptake by adding cold PSMA-11. Our data provides proof-of-concept and we propose that similar strategy be pursued in future clinical trials to prevent xerostomia and renal toxicity arising from [177Lu]-PSMA-617.
WaveletSEG: Automatic wavelet-based 3D nuclei segmentation and analysis for multicellular embryo quantification
Authors: Wu Tzu-Ching , Wang Xu , Li Linlin , Bu Ye , Umulis David M. 
Published: July 2020

AbstractIdentification of individual cells in tissues, organs, and in various developing systems is a well-studied problem because it is an essential part of objectively analyzing quantitative images in numerous biological contexts. We developed a size-dependent wavelet-based segmentation method that provides robust segmentation without any preprocessing, filtering or fine-tuning steps, and is robust to the signal-to-noise ratio (SNR). The wavelet-based method achieves robust segmentation results with respect to True Positive rate, Precision, and segmentation accuracy compared with other commonly used methods. We applied the segmentation program to zebrafish embryonic development IN TOTO for nuclei segmentation, image registration, and nuclei shape analysis. These new approaches to segmentation provide a means to carry out quantitative patterning analysis with single-cell precision throughout three dimensional tissues and embryos and they have a high tolerance for non-uniform and noisy image data sets.
A Simple Optimization Workflow to Enable Precise and Accurate Imputation of Missing Values in Proteomic Datasets
Authors: Dabke Kruttika , Kreimer Simion , Jones Michelle R. , Parker Sarah J. 
Published: July 2020

AbstractMissing values in proteomic data sets have real consequences on downstream data analysis and reproducibility. Although several imputation methods exist to handle missing values, there is no single imputation method that is best suited for a diverse range of data sets and no clear strategy exists for evaluating imputation methods for large-scale DIA-MS data sets, especially at different levels of protein quantification. To navigate through the different imputation strategies available in the literature, we have established a workflow to assess imputation methods on large-scale label-free DIA-MS data sets. We used two distinct DIA-MS data sets with real missing values to evaluate eight different imputation methods with multiple parameters at different levels of protein quantification; dilution series data set and an independent data set with actual experimental samples. We found that imputation methods based on local structures within the data, like local least squares (LLS) and random forest (RF), worked well in our dilution series data set whereas, imputation methods based on global structures within the data, like BPCA performed well in our independent data set. We also found that imputation at the most basic level of protein quantification – fragment level-improved accuracy and number of proteins quantified. Overall, this study indicates that the most suitable imputation method depends on the overall structure and correlations of proteins within the data set and can be identified with the workflow presented here.