bluuebunny/crossref_metadata_2025_split huggingface dataset:
A conditional survival distribution-based method for censored data imputation: overcoming the hurdle in machine learning-based survival analysis
Authors: Wang Yizhuo , Flowers Christopher R. , Li Ziyi , Huang Xuelin 
Published: February 2022

ABSTRACTData analyses by machine learning (ML) algorithms are gaining popularity in biomedical research. When time-to-event data are of interest, censoring is common and needs to be properly addressed. Most ML methods cannot conveniently and appropriately take the censoring information into consideration, potentially leading to inaccurate or biased results. We aim to develop a general-purpose method for imputing censored survival data, facilitating downstream ML analysis. In this study, we propose a novel method of imputing the survival times for censored observations. The proposal is based on their conditional survival distributions (CondiS) derived from Kaplan-Meier estimators. CondiS can replace censored observations with their best approximations from the statistical model, allowing for direct application of ML methods. When covariates are available, we extend CondiS by incorporating the covariate information through ML modeling (CondiS-X), which further improves the accuracy of the imputed survival time. Compared with existing methods with similar purposes, the proposed methods achieved smaller prediction errors and higher concordance with the underlying true survival times in extensive simulation studies. We also demonstrated the usage and advantages of the proposed methods through two real-world cancer datasets. The major advantage of CondiS is that it allows for the direct application of standard ML techniques for analysis once the censored survival times are imputed. We present a user-friendly R package to implement our method, which is a useful tool for ML-based biomedical research in this era of big data.
Four doses of the inactivated SARS-CoV-2 vaccine redistribute humoral immune responses away from the Receptor Binding Domain
Authors: Wang Ji , Deng Caiguangxi , Liu Ming , Liu Yihao , Li Liubing , Huang Zhangping , Shang Liru , Jiang Juan , Li Yongyong , Mo Ruohui , Zhang Hui , Liu Min , Peng Sui , Xiao Haipeng 
Published: February 2022

AbstractA recent MMWR reported that the effectiveness of a 3rd dose of SARS-CoV-2 mRNA vaccine waned quickly in the Omicron-predominant period. Similarly, a substantial decline of immune responses induced by a 3rd dose of inactivated vaccines was also observed in our study. In response to the fast waning immune response and the great threat of Omicron variant of concern (VOC) to frontline healthcare workers (HCWs), 38 HCWs who were in our previous cohort investigating responses to the first three doses of inactivated vaccines participated in the current study and volunteered to receive a 4th homologous booster. Here, we demonstrated that the 4th dose is safe and capable of recalling waned immune responses 6 months after the 3rd dose. However, a greater suppression on the induction of overall Neutralizing antibodies (NAbs) and NAbs targeting the receptor-binding domain (RBD) was found in participants with stronger immune responses after the 3rd dose. As a result, a stepwise elevation of RBD-NAbs from the 1st to the 3rd vaccination achieved a “turning point”. The peak RBD-NAbs level induced by the 4th dose was inferior to the peak of the 3rd dose. Accompanied with reduced induction of RBD-NAbs, the immune system shifted responses to the nucleocapsid protein (NP) and the N-terminal domain (NTD) of the spike protein. Although NTD directed antibodies are capable of neutralization, they only compensated the loss of RBD-NAbs to ancestral SARS-CoV-2 virus but not to the Omicron variant due to a substantial conformational change of Omicron NTD. This longitudinal clinical study monitored the immune response of the same cohort for every doses, shaping a relationship between the trajectory of immune focus and the dynamics of the neutralizing potency against the evolving virus. Our data reveal that immune responses could not be endlessly elevated, while suppression of heightened immune responses focusing on one subunit together with a shift of immune responses to other subunits would occur after repeated vaccination. Thus, an updated vaccine with more diverse epitopes capable of inducing NAbs against VOCs would be a future direction for boosters.
Generation of human nociceptor-enriched sensory neurons for the study of pain-related dysfunctions
Authors: Holzer Anna-Katharina , Karreman Christiaan , Suciu Ilinca , Furmanowsky Lara-Seline , Wohlfarth Harald , Loser Dominik , Dirks Wilhelm G , González Emilio Pardo , Leist Marcel 
Published: February 2022

AbstractIn vitro models of the peripheral nervous system would benefit from further refinements to better support studies on neuropathies. In particular, the assessment of pain-related signals is still difficult in human cell cultures. Here, we harnessed induced pluripotent stem cells (iPSCs) to generate peripheral sensory neurons enriched in nociceptors. The objective was to generate a culture system with signaling endpoints suitable for pharmacological and toxicological studies. Neurons generated by conventional differentiation protocols expressed moderate levels of P2X3 purinergic receptors and only low levels of TRPV1 capsaicin receptors, when maturation time was kept to the upper practically-useful limit of 6 weeks. As alternative approach, we generated cells with an inducible NGN1 transgene. Ectopic expression of this transcription factor during a defined time window of differentiation resulted in highly-enriched nociceptor cultures, as determined by functional (P2X3 and TRPV1 receptors) and immunocytochemical phenotyping, complemented by extensive transcriptome profiling. Single cell recordings of Ca2+-indicator fluorescence from >9,000 cells were used to establish the “fraction of reactive cells” in a stimulated population as experimental endpoint, that appeared robust, transparent and quantifiable. To provide an example of application to biomedical studies, functional consequences of prolonged exposure to the chemotherapeutic drug oxaliplatin were examined at non-cytotoxic concentrations. We found (i) neuronal (allodynia-like) hypersensitivity to otherwise non-activating mechanical stimulation that could be blocked by modulators of voltage-gated sodium channels; (ii) hyper-responsiveness to TRPV1 receptor stimulation. These findings and several other measured functional alterations indicate that the model is suitable for pharmacological and toxicological studies related to peripheral neuropathies.
Inverted genomic regions between reference genome builds in humans impact imputation accuracy and decrease the power of association testing
Authors: Sheng Xin , Xia Lucy , Conti David V. , Haiman Christopher A. , Kachuri Linda , Chiang Charleston W. K. 
Published: February 2022

AbstractOver the last two decades, the human reference genome has undergone multiple updates as we complete a linear representation of our genome. There are two versions of human references currently used in the biomedical literature, GRCh37/hg19 and GRCh38, and conversions between these versions are critical for quality control, imputation, and association analysis. In the present study we show that genomic coordinates for single nucleotide variants (SNVs) in regions inverted between different builds of the reference genome are erroneously converted by the TOPMed imputation server. Depending on the array type, we estimate the inappropriate conversions of variant coordinates would occur in about 2-5 Mb of the genome. Independent of the imputation server, however, in-house conversions of variant coordinates are routine yet impact of mapped variants to these inverted regions and its downstream analytical consequences are underrecognized. We observed that errors for palindromic variants in these inverted regions cannot be detected by standard quality control procedures and destabilize the local haplotype structure, leading to loss of imputation accuracy and power in association analyses. Though only a small proportion of the genome is affected, we show that these regions include important disease susceptibility variants that would be lost due to poor imputation. For example, we show that a known locus associated with prostate cancer on chr10 would have its association P-value drop from 2.86×10-7 to 0.0011 in a case-control analysis of 20,286 Africans and African Americans (10,643 cases and 9,643 controls). We devise a straight-forward heuristic based on the popular tool liftOver that can easily detect and correct these variants in the inverted regions between genome builds to locally improve imputation accuracy.
A pipeline for natural small molecule inhibitors of endoplasmic reticulum stress
Authors: da Silva Daniela Correia , Valentão Patrícia , Andrade Paula B. , Pereira David M. 
Published: February 2022

AbstractThe homeostasis of eukaryotic cells is inseverable of that of the endoplasmic reticulum (ER). The main function of this organelle is the synthesis and folding of a significant portion of cellular proteins, while also being the major calcium reservoir of the cell. Upon unresolved ER stress, a set of stress response signaling pathways that are collectively labeled as the unfolded protein response (UPR) is activated. Prolonged or intense activation of this molecular machinery may be deleterious. It is known that compromised ER homeostasis, and consequent UPR activation, characterize the pathogenesis of neurodegenerative disease.In an effort to discover new small molecules capable of countering ER stress, we subjected a panel of over 100 natural molecules to a battery of assays designed to evaluate several hallmarks of ER stress. The effect of the compounds on calcium homeostasis, key gene and protein expression, and levels of protein aggregation were evaluated in fibroblasts, and subsequently in neuronal cells. This framework resulted in the identification of several bioactive molecules capable of countering ER stress and deleterious events associated to it, among which delphinidin stands out as the most promising candidate against neurodegeneration.
Evaluating the roles of microbial functional breadth and home‐field advantage in leaf litter decomposition
Authors: Osburn Ernest D. , Hoch Peter J. , Lucas Jane M. , McBride Steven G. , Strickland Michael S. 
Published: February 2022

AbstractSoil biota are increasingly recognized as a primary control on litter decomposition at both local and regional scales, but the precise mechanisms by which biota influence litter decomposition have yet to be identified.There are multiple hypothesized mechanisms by which biotic communities may influence litter decomposition—for example, decomposer communities may be specially adapted to local litter inputs and therefore decompose litter from their home ecosystem at elevated rates. This mechanism is known as the home‐field advantage (HFA) hypothesis. Alternatively, litter decomposition rates may simply depend upon the range of metabolic functions present within a decomposer community. This mechanism is known as the functional breadth (FB) hypothesis. However, the relative importance of HFA and FB in litter decomposition is unknown, as are the microbial community drivers of HFA and FB. Potential relationships/trade‐offs between microbial HFA and FB are also unknown.To investigate the roles of HFA and FB in litter decomposition, we collected litter and soil from six different ecosystems across the continental US and conducted a full factorial litter × soil inoculum experiment. We measured litter decomposition (i.e. cumulative CO2‐C respired) over 150 days and used an analytical model to calculate the HFA and FB of each microbial decomposer community.Our results indicated clear functional differences among decomposer communities, that is, litter sources were decomposed differently by different decomposer communities. These differences were primarily due to differences in FB between different communities, while HFA effects were less evident.We observed a positive relationship between HFA and the disturbance‐sensitive bacterial phylum Verruomicrobia, suggesting that HFA may be an important mechanism in undisturbed environments. We also observed a negative relationship between bacterial r versus K strategists and FB, suggesting an important link between microbial life‐history strategies and litter decomposition functions.Microbial FB and HFA exhibited a strong unimodal relationship, where high HFA was observed at intermediate FB values, while low HFA was associated with both low and high FB. This suggests that adaptation of decomposers to local plant inputs (i.e. high HFA) constrains FB, which requires broad rather than specialized functionality. Furthermore, this relationship suggests that HFA effects will not be apparent when communities exhibit high FB and therefore decompose all litters well and also when FB is low and communities decompose all litters poorly. Overall, our study provides new insights into the mechanisms by which microbial communities influence the decomposition of leaf litter.Read the freePlain Language Summaryfor this article on the Journal blog.
Soil enzymes in response to climate warming: Mechanisms and feedbacks
Authors: Fanin Nicolas , Mooshammer Maria , Sauvadet Marie , Meng Cheng , Alvarez Gaël , Bernard Laëtitia , Bertrand Isabelle , Blagodatskaya Evgenia , Bon Lucie , Fontaine Sébastien , Niu Shuli , Lashermes Gwenaelle , Maxwell Tania L. , Weintraub Michael N. , Wingate Lisa , Moorhead Daryl , Nottingham Andrew T. 
Published: February 2022

Abstract

Soil enzymes are central to ecosystem processes because they mediate numerous reactions that are essential in biogeochemical cycles. However, how soil enzyme activities will respond to global warming is uncertain. We reviewed the literature on mechanisms linking temperature effects on soil enzymes and microbial communities, and outlined a conceptual overview on how these changes may influence soil carbon fluxes in terrestrial ecosystems.

At the enzyme scale, although temperature can have a positive effect on enzymatic catalytic power in the short term (i.e. via the instantaneous response of activity), this effect can be countered over time by enzyme inactivation and reduced substrate affinity. At the microbial scale, short‐term warming can increase enzymatic catalytic power via accelerated synthesis and microbial turnover, but shifts in microbial community composition and growth efficiency may mediate the effect of warming in the long term.

Although increasing enzyme activities may accelerate labile carbon decomposition over months to years, our literature review highlights that this initial stage can be followed by the following phases: (a) a reduction in soil carbon loss, due to changing carbon use efficiency among communities or substrate depletion, which together can decrease microbial biomass and enzyme activity and (b) an acceleration of soil carbon loss, due to shifts in microbial community structure and greater allocation to oxidative enzymes for recalcitrant carbon degradation. Studies that bridge scales in time and space are required to assess whether there will be an attenuation or acceleration of soil carbon loss through changes in enzyme activities in the very long term.

We conclude that soil enzymes determine the sensitivity of soil carbon to warming, but that the microbial community and enzymatic traits that mediate this effect change over time. Improving representation of enzymes in soil carbon models requires long‐term studies that characterize the response of wide‐ranging hydrolytic and oxidative enzymatic traits—catalytic power, kinetics, inactivation—and the microbial community responses that govern enzyme synthesis.

Read the free Plain Language Summary for this article on the Journal blog.
A physics‐guided neural network‐based approach to velocity model calibration for microseismic data
Authors: Zhang Hongliang , Akram Jubran , Innanen Kristopher A. 
Published: February 2022

ABSTRACTThe physics‐guided neural network framework combines the effectiveness of data‐driven and physics‐based models, and it is, therefore, becoming increasingly popular in geophysical applications. We present a physics‐guided neural network–based approach to calibrate velocity models for microseismic data. In our implementation, the physics‐guided neural network comprises of a user‐selected number of fully connected layers, a scaling and shifting layer and a forward modelling operator layer. We input the observed P‐ and S‐wave arrival times to the neural network. In the forward pass, the network's output layer produces normalized P‐ and S‐wave velocities for the subsurface model. The scaling and shifting layer converts the normalized output to realistic velocity values. The forward modelling operator (i.e. a ray‐shooting algorithm) layer computes traveltimes using the velocities from the preceding scaling and shifting layer and the known source–receiver locations. We then evaluate a loss function that compares the predicted traveltimes with the input observed arrival times, and update network's weights and bias parameters. We also use a weight‐based saliency measure to evaluate whether the selected network architecture (i.e. number of hidden layers and neurons) is optimal for the model calibration problem. Finally, using synthetic data examples, we demonstrate that our unsupervised physics‐guided neural network–based approach can provide robust velocity model and uncertainty estimates.
Migrating to Global Reporting Initiative Guidelines: Does International Harmonization of CSR Information Pay?
Authors: Jeriji Maher , Louhichi Waël , Ftiti Zied 
Published: February 2022

AbstractThousands of organizations worldwide currently use the Global Reporting Initiative (GRI) standards to report on sustainability information. We use data from 39 countries over the 2010–2018 period to examine the incremental value relevance of the international harmonization of corporate social responsibility (CSR) disclosure. A propensity score matching–difference in differences (PSM‐DID) research design was used to avoid selection bias and endogeneity concerns. We find that migrating to the GRI guidelines destroys firm value. This relationship is stronger for firms with poor CSR performance, which suggests that market players, particularly institutional investors, consider GRI migration as a cost driver – at least in the short term. The introduction of other potentially confounding institutional factors highlights the effectiveness of the negative relationship between firm value and GRI migration for countries with more opaque financial markets and less sustainable business environments. Our findings have several implications for policymakers, academics and practitioners in understanding both the motivations and the consequences of CSR harmonization reporting on financial markets.
Treatment pattern, satisfaction, and productivity loss of patients with ankylosing spondylitis treated with tumor necrosis factor inhibitors in Korea: A multicenter cross‐sectional observational study
Authors: Lee Sang‐Hoon , Kim Yong‐Gil , Lee Seung‐Geun , Lee Soo Hyun , Kim Young‐Joo , Jeon Ja‐Young , Jo Joo‐Young , Yoo Hyun‐Jeong , Lee Juneyoung , Kim Tae‐Hwan 
Published: February 2022

AbstractAimTo provide in‐depth understanding of real‐world tumor necrosis factor inhibitor (TNFi) treatment patterns in patients with ankylosing spondylitis (AS) and treatment satisfaction, productivity loss, and associated factors.MethodsThis was a multicenter observational hybrid retrospective chart review and cross‐sectional survey study. Disease activity and physical functioning were measured using the Bath AS Disease Activity Index and Bath AS Functional Index, respectively. Treatment satisfaction was determined with the Treatment Satisfaction Questionnaire for Medication (TSQM). Productivity loss was evaluated using the Korean version of the World Health Organization–Health and Work Performance Questionnaire.ResultsA total of 497 patients were enrolled (mean age 40.3 years, 85.3% male, mean AS duration 10 years). The mean duration of TNFi treatment was 6.2 years. Among the four TNFi considered, adalimumab (39.6%) and etanercept (23.5%) were most commonly used at study enrollment. The TSQM convenience domain score was lower than scores in the effectiveness, adverse effects, and global satisfaction domains. Subcutaneous syringe‐type injection and intravenous injection were associated with lower patient convenience satisfaction than subcutaneous pen‐type injection. Increased costs of lost productivity time were associated with female sex, unemployed status, and higher disease activity.ConclusionsThe most frequently prescribed TNFi was adalimumab, followed by etanercept. Etanercept was used for the longest duration. More convenient treatment options may enhance overall treatment satisfaction. Considerable loss in productivity due to AS was observed in this study. To reflect patients’ perspectives, further attention should be paid to factors associated with treatment satisfaction and productivity loss when selecting treatment options.
“Readiness for enhanced healthy aging” nursing diagnosis: Content validation by experts
Authors: Cardoso Rosane Barreto , Caldas Célia Pereira , Brandão Marcos Antônio Gomes , de Souza Priscilla Alfradique , Santana Rosimere Ferreira 
Published: February 2022

AbstractPurposeTo validate the content nursing diagnosis “Readiness for enhanced healthy aging.”MethodsDescriptive, methodological study of diagnostic content validation, using the Fehring model. The sample consisted of 74 nurses experts in gerontology, with knowledge in NANDA‐I nursing diagnoses.FindingsThe title, one definition, and the three defining characteristics proposed for the diagnosis were validated, as well as the suggestion of domain and location class in NANDA‐I Taxonomy II. The Diagnostic Content Validity Index was 0.81.ConclusionsThe validation of the diagnostic content by experts was fundamental for adequacy of the elements of the proposed diagnosis, which supported the elaboration of the diagnostic framework for submission to the NANDA‐I taxonomy.Implication for nursing practiceThe diagnosis “Readiness for enhanced healthy aging” can help nurses understand the phenomenon of “Healthy Aging” and, consequently, will support the planning and implementation of interventions aimed at promoting the health of the elderly population and those in the aging process. In addition, this diagnosis will offer nurses the opportunity to rethink health promotion strategies in their care plan, making a commitment to the population regarding the promotion of healthy aging, as recommended by the Word Health Organization.