bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of neutralizing antibody titers for estimating vaccine effectiveness for the Omicron SARS-CoV-2 variant, BA.1
Authors: Gardner Billy J. , Kilpatrick A. Marm 
Published: December 2021

AbstractBackgroundThe emergence of new virus variants, including the Omicron variant (B.1.1.529) of SARS-CoV-2, can lead to immune escape and reduced vaccine effectiveness. Neutralizing antibody titers could be used to quickly estimate vaccine effectiveness (VE), because they can be easily measured following the emergence of a new virus variant and have been shown to be a correlate of protection for SARS-CoV-2 and other pathogens. However, few studies have examined VE-neutralizing antibody titer relationships with multiple virus variants, and none have validated relationships for immune evasive variants.MethodsWe leveraged variation among vaccines and virus variants to estimate VE-neutralizing antibody titer relationships across a 54-fold range of neutralizing antibody titers for two endpoints for COVID-19: symptomatic disease, and hospitalization. We predicted VEs for Omicron three days after the first neutralizing antibody titer became available. We tested these predictions using subsequently collected observational VE data.FindingsFor two mRNA vaccines (mRNA-1273, BNT162b2), fitted models predicted that infection with the BA.1 Omicron variant would increase the risk of hospitalization 2.8-4.4-fold and increase the risk of symptomatic disease 1.7-4.2-fold compared to the Delta variant. However, a third vaccine dose was predicted to restore protection. Out-of-sample validation data indicated that model predictions were quite accurate, with all predictions being within 10% of observed VE estimates, and all empirical estimates fell within the model prediction intervals.InterpretationThese analyses demonstrate that models using neutralizing antibody titers can provide rapid VE estimates which can inform vaccine design and selection.FundingCalifornia Department of Health, National Science Foundation
The human thalamus orchestrates neocortical oscillations during NREM sleep
Authors: Schreiner Thomas , Kaufmann Elisabeth , Noachtar Soheyl , Mehrkens Jan-Hinnerk , Staudigl Tobias 
Published: December 2021

ABSTRACTA hallmark of non-rapid eye movement sleep is the coordinated interplay of slow oscillations (SOs) and sleep spindles. Traditionally, a cortico-thalamo-cortical loop is suggested to coordinate these rhythms: neocortically-generated SOs trigger spindles in the thalamus that are projected back to neocortex. Here, we used intrathalamic recordings from human epilepsy patients to test this canonical interplay. We show that SOs in the anterior thalamus precede neocortical SOs (peak -50 ms), whereas concurrently-recorded SOs in the mediodorsal thalamus are led by neocortical SOs (peak +50 ms). Sleep spindles, detected in both thalamic nuclei, preceded their neocortical counterparts (peak -100 ms) and were initiated during early phases of thalamic SOs. Our findings indicate an active role of the anterior thalamus in organizing sleep rhythms in the neocortex and highlight the functional diversity of thalamic nuclei in humans. The thalamic coordination of sleep oscillations could have broad implications for the mechanisms underlying memory consolidation.
Insights into bear evolution from a Pleistocene polar bear genome
Authors: Lan Tianying , Leppälä Kalle , Tomlin Crystal , Talbot Sandra L. , Sage George K. , Farley Sean D. , Shideler Richard T. , Bachmann Lutz , Wiig Øystein , Albert Victor A. , Salojärvi Jarkko , Mailund Thomas , Drautz-Moses Daniela I. , Schuster Stephan C. , Herrera-Estrella Luis , Lindqvist Charlotte 
Published: December 2021

AbstractThe polar bear (Ursus maritimus) has become a symbol of the threat to biodiversity from climate change. Understanding polar bear evolutionary history may provide insights into apex carnivore responses and prospects during periods of extreme environmental perturbations. In recent years, genomic studies have examined bear speciation and population history, including evidence for ancient admixture between polar bears and brown bears (Ursus arctos). Here, we extend our earlier studies of a 130,000–115,000-year-old polar bear from the Svalbard Archipelago using a 10X coverage genome sequence and ten new genomes of polar and brown bears from contemporary zones of overlap in northern Alaska. We demonstrate a dramatic decline in effective population size for this ancient polar bear’s lineage, followed by a modest increase just before its demise. A slightly higher genetic diversity in the ancient polar bear suggests a severe genetic erosion over a prolonged bottleneck in modern polar bears. Statistical fitting of data to alternative admixture graph scenarios favors at least one ancient introgression event from brown bears into the ancestor of polar bears, possibly dating back over 150,000 years. Gene flow was likely bidirectional, but allelic transfer from brown into polar bear is the strongest detected signal, which contrasts with other published works. These findings may have implications for our understanding of climate change impacts: polar bears, a specialist Arctic lineage, may not only have undergone severe genetic bottlenecks, but also been the recipient of generalist, boreal genetic variants from brown bear during critical phases of Northern Hemisphere glacial oscillations.SignificanceInterspecific hybridization is a widespread phenomenon, but measuring its extent, directionality, and adaptive importance remains challenging. Ancient genomes, however, can help illuminate the history of modern organisms. Here, we present a genome retrieved from a 130,000–115,000-year-old polar bear and perform genome analyses of modern polar and brown bears throughout their geographic range. We find that the principal direction of ancient allele sharing was from brown bear into polar bear, although gene flow between them has likely been bidirectional. This inverts the current paradigm of unidirectional gene flow from polar into brown bear, and it suggests that polar bears were recipients of external genetic variation prior to their extensive population decline.
Multiple genes in cis mediate the effects of a single chromatin accessibility variant on aberrant synaptic development and function in human neurons
Authors: Zhang Siwei , Zhang Hanwen , Forrest Marc P. , Zhou Yifan , Bagchi Vikram A. , Kozlova Alena , Santos Marc Dos , Piguel Nicolas H. , Dionisio Leonardo E. , Sanders Alan R. , Pang Zhiping P. , He Xin , Penzes Peter , Duan Jubao 
Published: December 2021

AbstractDespite hundreds of risk loci from genome-wide association studies of neuropsychiatric disorders, causal variants/genes remain largely unknown. Here, in NEUROG2-induced human neurons, we identified 31 risk SNPs in 26 schizophrenia (SZ) risk loci that displayed allele-specific open chromatin (ASoC) and were likely to be functional. Editing the strongest ASoC SNP rs2027349 near vacuolar protein sorting 45 homolog (VPS45) altered the expression of VPS45, lncRNA AC244033.2, and a distal gene, C1orf54, in human neurons. Notably, the global gene expression changes in neurons were enriched for SZ risk and correlated with post-mortem brain gene expression signatures of neuropsychiatric disorders. Neurons carrying the risk allele exhibited increased dendritic complexity, synaptic puncta density, and hyperactivity, which were reversed by knocking-down distinct cis-regulated genes (VPS45, AC244033.2, or C1orf54), suggesting a phenotypic contribution from all three genes. Interestingly, transcriptomic analysis of knockdown cells suggested a non-additive effects of these genes. Our study reveals a compound effect of multiple genes at a single SZ locus on synaptic development and function, providing a mechanistic link between a non-coding SZ risk variant and disease-related cellular phenotypes.
Ion channel distributions in cortical neurons are optimized for energy-efficient active dendritic computations
Authors: Bast Arco , Oberlaender Marcel 
Published: December 2021

AbstractThe mammalian brain has an enormous demand for energy, which is thought to impose strong selective pressure by which the neurons evolve in ways that ensure robust function at minimal energy cost. However, which principles drive the ion channel distributions in the dendrites to implement different neuronal functions is yet unclear. Here we found that an energy-efficient generation of dendritic calcium action potentials in cortical pyramidal neurons requires a low expression of slow inactivating potassium channels. We demonstrate that this relationship between energy cost and neuronal function is independent of the dendritic morphology and the expression patterns of other ion channels that implement additional perisomatic and dendritic functions. Moreover, we found that calcium action potentials can arise from a wide spectrum of ion channel expression patterns, including configurations with high potassium channel densities in the dendrites. These configurations can account equally well for the characteristic intrinsic physiology of the pyramidal neurons. However, only configurations with low potassium channel densities in the distal dendrites are observed empirically. Thus, our findings indicate that cortical neurons do not utilize all theoretically possible ways to implement their functions, but instead select those optimized for energy-efficient active dendritic computations.
Three simple steps to improve the interpretability of EEG-SVM studies
Authors: Joucla Coralie , Gabriel Damien , Ortega Juan-Pablo , Haffen Emmanuel 
Published: December 2021

AbstractResearch in machine-learning classification of electroencephalography (EEG) data offers important perspectives for the diagnosis and prognosis of a wide variety of neurological and psychiatric conditions, but the clinical adoption of such systems remains low. We propose here that much of the difficulties translating EEG-machine learning research to the clinic result from consistent inaccuracies in their technical reporting, which severely impair the interpretability of their often-high claims of performance. Taking example from a major class of machine-learning algorithms used in EEG research, the support-vector machine (SVM), we highlight three important aspects of model development (normalization, hyperparameter optimization and cross-validation) and show that, while these 3 aspects can make or break the performance of the system, they are left entirely undocumented in a shockingly vast majority of the research literature. Providing a more systematic description of these aspects of model development constitute three simple steps to improve the interpretability of EEG-SVM research and, in fine, its clinical adoption.
Wavelength-dependent DNA photodamage in a 3-D human skin model over the far-UVC and germicidal-UVC wavelength ranges from 215 to 255 nm
Authors: Welch David , de Muro Marilena Aquino , Buonanno Manuela , Brenner David J 
Published: December 2021

ABSTRACTThe effectiveness of UVC to reduce airborne-mediated disease transmission is well-established. However conventional germicidal UVC (~254 nm) cannot be used directly in occupied spaces because of the potential for damage to the skin and eye. A recently studied alternative with the potential to be used directly in occupied spaces is far-UVC (200 to 235 nm, typically 222 nm), as it cannot penetrate to the key living cells in the epidermis. Optimal far-UVC use is hampered by limited knowledge of the precise wavelength dependence of UVC-induced DNA damage, and thus we have used a monochromatic UVC exposure system to assess wavelength-dependent DNA damage in a realistic 3-D human skin model. We exposed a 3-D human skin model to mono-wavelength UVC exposures of 100 mJ/cm2, at UVC wavelengths from 215 to 255 nm (5-nm steps). At each wavelength we measured yields of DNA-damaged keratinocytes, and their distribution within the layers of the epidermis. No increase in DNA damage was observed in the epidermis at wavelengths from 215 to 235 nm, but at higher wavelengths (240-255 nm) significant levels of DNA damage were observed. These results support use of far-UVC light to safely reduce the risk of airborne disease transmission in occupied locations.
Pseudomonas response regulators produced in an E. coli heterologous expression host exhibit host-derived post-translational phosphorylation
Authors: Garber Megan E. , Fregoso Rodrigo , Lake Julie , Kakouridis Anne , Mukhopadhyay Aindrila 
Published: December 2021

AbstractIn this report, we systematically characterize 32 response regulators (RRs) from a metal tolerant groundwater isolate, Pseudomonas stutzeri RCH2 to assess the impact of host-derived post-translational phosphorylation. As observed by distinct shifted bands in a phos-tag gel, 12 of the 24 detected RRs show homogenous mixtures of phosphorylated proteins or heterogenous mixtures of unphosphorylated and phosphorylated proteins. By evaluating the phosphorylation state of CzcR and CopR II under varying assay parameters, we found that changes to pH and exogenous addition of phospho-donors (e.g. acetyl phosphate) have little to no effect on phosphorylation state. By applying protein production conditions that decrease the pool of intracellular acetyl-phosphate in E. coli, we found a reduction in the phosphorylated population of CopR II when magnesium was added to the media, but observed no change in phosphorylated population when CopR II is expressed in E. coli BL21 (DE3) Δpta, a mutant with a metabolic disruption to the acetyl-phosphate pathway. Therefore, the specific mechanism of post-translational phosphorylation of RRs in E. coli remains obscure. These findings show the importance of characterizing the phosphorylations state of proteins when heterologously expressed, since their biochemical and physiological properties are dependent on post-translational modification.
Family business valuation in emerging economies: the arcor case
Authors: Roca Florencia 
Published: December 2021

Learning outcomes
This case can be used to help students achieve the following objectives: To project financial statements and assemble different pieces of financial information to create a valuation model (objective #1, create), To calculate a value for Arcor shares, supporting the estimated value with the chosen assumptions and methodologies (objective #2, evaluate), To draw connections between four different approaches to valuation (DCF, EVA, RV and VI), contrasting them and weighting their advantages and limitations (objective #3, analyze), To examine the relationship between forecasted financial statements and valuation (objective #3, analyze), To discuss the calculation of the Weighted Average Cost of Capital in a new situation as is an emerging economy, with the corresponding country-risk adjustment (objective #4, apply), To discuss the sources of value creation in a family-owned private company in a developing economy (objective #4, apply), To understand the dilemma that the head of a company was facing, identifying the three possible financing alternatives discussed in the text as follows: corporate bonds, earnings reinvestment and an IPO (objective #5, understand). To recall basic facts, as the main character’s opinion on the direction of the local economy or the fact that Arcor already complies with the information requirements of a public company (objective #7, remember).

Case overview/synopsis
This case is based on the valuation of the world’s largest candy maker, Arcor S.A.I.C., originally a Latin American company, which remains a private family business. The key problem presented by the case is the use of different valuation approaches to price Arcor shares, in view of a possible Initial Public Offer. The case illustrates the application of four main valuation approaches as follows: Discounted Cash Flow (DCF), Economic Value Added (EVA), Relative Valuation (RV) and Value Investing (VI). Additionally, it includes a fundamental analysis of eight years of historical financial information and the preparation of forecasted financial statements. Set in a developing economy, the Arcor case introduces the complexities of calculating the cost of capital with the inclusion of country risk, as well as the financial analysis distortions caused by an environment of high inflation.

Complexity academic level
The Arcor case is appropriate to be used in graduate courses of Corporate Finance, Valuation or Private Equity.

Supplementary materials
Teaching notes are available for educators only.

Subject code
CSS 1: Accounting and Finance.
Cell size as driver and sentinel of phytoplankton community structure and functioning
Authors: Hillebrand Helmut , Acevedo‐Trejos Esteban , Moorthi Stefanie D. , Ryabov Alexey , Striebel Maren , Thomas Patrick K. , Schneider Marie‐Luise 
Published: December 2021

AbstractBody size is a decisive functional trait in many organisms, especially for phytoplankton, which span several orders of magnitude in cell volume. Therefore, the analysis of size as a functional trait driving species’ performance has received wide attention in aquatic ecology, amended in recent decades by studies documenting changes in phytoplankton size in response to abiotic or biotic factors in the environment.We performed a systematic literature review to provide an overarching, partially quantitative synthesis of cell size as a driver and sentinel of phytoplankton ecology. We found consistent and significant allometric relationships between cell sizes and the functional performance of phytoplankton species (cellular rates of carbon fixation, respiration and exudation as well as resource affinities, uptake and content). Size scaling became weaker, absent or even negative when addressing C‐ or volume‐specific rates or growth. C‐specific photosynthesis and population growth rate peaked at intermediate cell sizes around 100 µm3.Additionally, we found a rich literature on sizes changing in response to warming, nutrients and pollutants. Whereas small cells tended to dominate under oligotrophic and warm conditions, there are a few notable exceptions, which indicates that other environmental or biotic constraints alter this general trend. Grazing seems a likely explanation, which we reviewed to understand both how size affects edibility and how size structure changes in response to grazing. Cell size also predisposes the strength and outcome of competitive interactions between algal species. Finally, we address size in a community context, where size‐abundance scaling describes community composition and thereby the biodiversity in phytoplankton assemblages.We conclude that (a) size is a highly predictive trait for phytoplankton metabolism at the cellular scale, with less strong and nonlinear implications for growth and specific metabolism and (b) size structure is a highly suitable sentinel of phytoplankton responses to changing environments.A freePlain Language Summarycan be found within the Supporting Information of this article.
Maternal effects of climate warming and nitrogen deposition vary with home and introduced ranges
Authors: Zhou Xiao‐Hui , Li Jing‐Ji , Gao Yuan‐Yuan , Peng Pei‐Hao , He Wei‐Ming 
Published: December 2021

AbstractMaternal effects allow offspring to cope with rapidly changing environments. While the immediate effects of long‐term climate warming and nitrogen (N) deposition are well documented, their maternal effects have been little studied.We conducted a 6‐year maternal experiment withSolidago canadensis(Canadian goldenrod), native to North America (home range) and invasive in China (introduced range), and then performed two offspring experiments to address how maternal warming, maternal N‐addition and population source interacted to influence offspring performance.Maternal effects of warming and N‐addition on seed traits, leaf dry matter content and whole‐plant biomass were stronger inS. canadensisoffspring from China (introduced range) than in offspring from North America (home range). Matched maternal–offspring environments allowed offspring to perform better compared to mismatched environments; offspring grown under warming flowered and produced seeds within a growing season only when their maternal plants were previously exposed to warming. Offspring environments influenced its performance and also modulated maternal effects.We suggest that the maternal effects of simulated climate warming and N deposition could vary with home and introduced ranges. Our findings imply that maternal warming could advance the reproductive phenology of offspring.A freePlain Language Summarycan be found within the Supporting Information of this article.
Talking about race, culture and racism in family therapy
Authors: Roy‐Chowdhury Sim 
Published: December 2021

AbstractFamily therapy practice in the UK, as elsewhere in the world, takes place within the context of structural and systemic racism. Hence the practice of family therapy has the potential to mirror racist and colonialist tropes found within society. There are low levels of satisfaction by people from Black and ethnic minority backgrounds to the level of sensitivity to culture and racism that takes place in therapy. This paper explores ways a systemic psychotherapy might be more sensitive to differences in race and culture. Drawing upon systemic and anthropological constructions of culture, suggestions are made for practice that is more questioning of the barely conscious or unconscious assumptions made by the therapist, which can then lead to open scrutiny of these assumptions. In doing so, I draw upon my own experiences, and those of my own family, of racism, of culture and of movement across cultures.
Practitioner points

Structural racism in society will find its way into the therapy room unless therapists are open to an examination of their own prejudices and often unconscious assumptions.

Such an examination then opens the way to forms of practice that are more sensitive to differences of race and culture.

A form of practice more sensitive to race and culture is proposed as a systemic response to racism, whilst keeping in mind the need for change at a social and political level.
Not Threats, but Resources: An Investigation of How Leaders React to Employee Constructive Voice
Authors: Xu Angela J. , Loi Raymond , Cai Zhenyao 
Published: December 2021

AbstractThis research aims to investigate whether or not leaders, one of the main recipients of employee voice, develop good relationships with those who speak up. Drawing on resource theory and social exchange theory, we contend that constructive voice provides both information and affect resources to the leader, which in turn promote a resource‐based exchange relationship with the leader (i.e., leader–member exchange; LMX). We further propose that leaders with an originality cognitive style are more likely to capture the resource value of constructive voice, while leaders who closely follow rules might not view constructive voice in a positive way, thus affecting their LMX relationships with the focal employee. Through a two‐wave field survey among 199 leader–follower dyads (Study 1) and a vignette‐based experiment among 221 leaders (Study 2), we found that leaders, especially leaders who advocated high originality, developed high‐quality LMX relationships with those who engaged in constructive voice due to their perceptions of affect but not information resource.