bluuebunny/crossref_metadata_2025_split huggingface dataset:
A mouse model of oral contraceptive exposure: depression, motivation, and the stress response
Authors: Schuh Kristen M. , Ahmed Jabir , Kwak Esther , Xu Cecilia X. , Davis Tronjay T. , Aronoff Chloe B. , Tronson Natalie C. 
Published: January 2023

ABSTRACTHormonal contraceptives, including oral contraceptives (OCs), regulate hormonal cycles and broadly affect physiological processes, including stress responsivity. Whereas many users describe overall improved mood, up to 10% of OC users experience adverse effects, including depression and anxiety. Given the link between regulation of hypothalamic-pituitary-adrenal (HPA) axis, stress exposure, and risk for depression, it is likely that OC-effects on stress mediate increased risk or increased resilience to these disorders. In this study, we developed and characterized a tractable mouse model of OC exposure with which to identify the mechanisms underlying OC modulation of brain, behavior, and mood. Specifically, we aimed to determine whether translationally relevant doses of OC-hormones in mice mimic changes in stress responsivity observed in humans taking OCs and describe behavioral changes during OC exposure. Young adult female C57Bl/6N mice received daily ethinyl estradiol (EE) and levonorgestrel (LVNG) in 10% sucrose, EE and drospirenone (DRSP) in 10% sucrose, or 10% sucrose alone. Translationally relevant doses of EE+LVNG-exposure, but not EE+DRSP, suppressed the acute stress response, consistent with effects observed in human OC users. EE+LVNG caused a specific anhedonia-like effect, without broad changes in stress-coping behavior, other depression-like behaviors, or anxiety-like behaviors. The suppression of regular estrous cycling, together with the blunting of the corticosterone response to acute stress, demonstrate the utility of this model for future studies to identify the mechanisms underlying OC interactions with stress, motivation, and risk for depression.
Tackling hysteresis in conformational sampling — how to be forgetful with MEMENTO
Authors: Lichtinger Simon M. , Biggin Philip C. 
Published: January 2023

AbstractThe structure of proteins has long been recognised to hold the key to understanding and engineering their function, and rapid advances in structural biology (and protein structure prediction) are now supplying researchers with an ever-increasing wealth of structural information. Most of the time, however, structures can only be determined in free energy minima, one at a time. While conformational flexibility may thus be inferred from static end-state structures, their interconversion mechanisms — a central ambition of structural biology — are often beyond the scope of direct experimentation. Given the dynamical nature of the processes in question, many studies have attempted to explore conformational transitions using molecular dynamics (MD). However, ensuring proper convergence and reversibility in the predicted transitions is extremely challenging. In particular, a commonly used technique to map out a path from a starting to a target conformation called targeted MD (tMD) can suffer from starting-state dependence (hysteresis) when combined with techniques such as umbrella sampling (US) to compute the free energy profile of a transition.Here, we study this problem in detail on conformational changes of increasing complexity. We also present a new, history-independent approach that we term “MEMENTO” (Morphing End states by Modelling Ensembles with iNdependent TOpologies) to generate paths that alleviate hysteresis in the construction of conformational free energy profiles. MEMENTO utilises template-based structure modelling to restore physically reasonable protein conformations based on coordinate interpolation (morphing) as an ensemble of plausible intermediates, from which a smooth path is picked. We compare tMD and MEMENTO on well-characterized test cases (the toy peptide deca-alanine and the enzyme adenylate kinase) before discussing its use in more complicated systems (the kinase P38αand the bacterial leucine transporter LeuT). Our work shows that for all but the simplest systems tMD paths should not in general be used to seed umbrella sampling or related techniques, unless the paths are validated by consistent results from biased runs in opposite directions. MEMENTO, on the other hand performs well as a flexible tool to generate intermediate structures for umbrella sampling. We also demonstrate that extended end-state sampling combined with MEMENTO can aid the discovery of collective variables on a case-by-case basis.TOC Graphic
Examining Horizontal Transmission ofNippostrongylus brasiliensisin Mice to Assess Biosecurity Risks
Authors: Floyd Rebecca J , Ricart Arbona Rodolfo J , Carrasco Sebastian E , Lipman Neil S 
Published: January 2023

AbstractNippostrongylus brasiliensis(Nb) infected mice are commonly used to study immune responses. There is no consensus regarding the biosecurity measures that should be employed when housing Nb-infected mice and rats. Transmission is reported to not occur when infected mice are co-housed with naive mice. We sought to determine what conditions, if any, favor horizontal transmission. Female NOD.Cg-PrkdcscidIl2rgtm1Wjl/Sz (NSG; n=12) and C57BL/6J (B6; n=12) mice inoculated with 750 Nb L3larvae were cohoused with naïve NSG (n=24) and B6 (n=24) mice at a ratio of 1 infected:2 naïve mice per cage for 28 days within static microsiolator (MI) cages changed on a 14-day interval. We also assessed whether larval development to the L3stage could occur when Nb egg-containing fecal pellets are maintained under 4 different environmental conditions (dry, moist, soiled bedding, and control) and whether infection results when naïve NSG mice (n=9) are housed in MI cages with infective L3larvae-spiked (10,000/cage) soiled bedding. NSG mice (n=3) were also gavaged with Nb eggs to model the potential for infection to occur following coprophagy. Both naïve NSG (9 of 24) and B6 (10 of 24) mice cohoused with an infected cagemate passed Nb eggs in feces as early as 1 day and intermittently for varying periods following cohousing, presumably a result of coprophagy as adult worms were not detected at euthanasia. While eggs were able to develop into L3larvae under 2 environmental conditions (moist and control), none of the NSG mice housed in cages with L3-spiked bedding or gavaged with eggs became infected with Nb. Findings demonstrate that horizontal transmission does not occur when mice are housed with Nb-shedding cagemates in static MI cages with a 14-day cage changing interval. Results from this study can be used to inform biosecurity practices when working with the Nb-infected mouse model.
Short- and longer-term all-cause mortality among SARS-CoV-2-infected persons and the pull-forward phenomenon in Qatar
Authors: Chemaitelly Hiam , Faust Jeremy Samuel , Krumholz Harlan M. , Ayoub Houssein H. , Tang Patrick , Coyle Peter , Yassine Hadi M. , Thani Asmaa A. Al , Al-Khatib Hebah A. , Hasan Mohammad R. , Al-Kanaani Zaina , Al-Kuwari Einas , Jeremijenko Andrew , Kaleeckal Anvar Hassan , Latif Ali Nizar , Shaik Riyazuddin Mohammad , Abdul-Rahim Hanan F. , Nasrallah Gheyath K. , Al-Kuwari Mohamed Ghaith , Butt Adeel A. , Al-Romaihi Hamad Eid , Al-Thani Mohamed H. , Al-Khal Abdullatif , Bertollini Roberto , Abu-Raddad Laith J. 
Published: January 2023

AbstractBackgroundRisk of short- and long-term all-cause mortality after a primary SARS-CoV-2 infection is inadequately understood.MethodsA national, matched, retrospective cohort study was conducted in Qatar to assess the risk of all-cause mortality in the national cohort of people infected with SARS-CoV-2 compared with a reference national control cohort of uninfected persons. Associations were estimated using Cox proportional-hazards regression models.ResultsAmong unvaccinated persons, within 90 days after primary infection, adjusted hazard ratio (aHR) comparing incidence of death in the primary-infection cohort with the infection-naïve cohort was 1.19 (95% CI: 1.02-1.39). The aHR was 1.34 (95% CI: 1.11-1.63) in persons more clinically vulnerable to severe COVID-19 and 0.94 (95% CI: 0.72-1.24) in those less clinically vulnerable to severe COVID-19. In subsequent follow-up, the aHR was 0.50 (95% CI: 0.37-0.68). The aHR was 0.41 (95% CI: 0.28-0.58) in months 3-7 after the primary infection and 0.76 (95% CI: 0.46-1.26) in subsequent months. The aHR was 0.37 (95% CI: 0.25-0.54) in persons more clinically vulnerable to severe COVID-19 and 0.77 (95% CI: 0.48-1.24) in those less clinically vulnerable to severe COVID-19. Among vaccinated persons, no evidence was found for differences in incidence of death in the primary-infection versus infection-naïve cohorts, even among persons more clinically vulnerable to severe COVID-19.ConclusionsCOVID-19 mortality in Qatar appears primarily driven by forward displacement of deaths of individuals with relatively short life expectancy and more clinically vulnerable to severe COVID-19. Vaccination negated the mortality displacement by preventing early deaths.
Free-Cog reformulated: analyses as independent or stepwise tests of cognitive and executive function
Authors: Larner Andrew J , Burns Alistair 
Published: January 2023

AbstractFree-Cog is a recently described, hybrid screening instrument incorporating tests of cognitive and executive function. In this study, Free-Cog was reformulated as separate tests of cognitive function and executive function to examine whether this might improve screening accuracy for cognitive impairment (dementia and mild cognitive impairment) compared to the standard, unitary Free-Cog. The two separate tests, designated “Free-Cog-Cog” and “Free-Cog-Exec,” were either combined using the Boolean logical “AND” and “OR” operators (serial and parallel combination) or used to construct a stepwise decision tree. Serial combination improved specificity and positive predictive value whereas parallel combination improved sensitivity, findings typically observed when applying these operators. Stepwise application identified groups with high and low probability of cognitive impairment but failed to adequately differentiate those in the intermediate uncertain diagnosis group. Although the dataset used was relatively small, the findings of this study suggest little benefit for reformulations of Free-Cog compared to the standard, unitary instrument.
Do medical marijuana laws increase prescription stimulant use?
Authors: Alexander Garrett D. , Cavanah Luke R. , Goldhirsh Jessica L. , Huey Leighton Y. , Piper Brian J. 
Published: January 2023

AbstractBackgroundChronic cannabis use can present with cognitive impairments that resemble ADHD. Our objective was to determine if medical cannabis (MC) legalization increased prescription stimulant distribution.MethodsWe extracted distribution of methylphenidate, amphetamine, and lisdexamfetamine from the Drug Enforcement Administration’s comprehensive database for 2006 to 2021 and compared the three-year population-corrected slopes of stimulant distribution before and after MC program implementation.ResultsWe found a very large main effect of time (p≤0.001), but, contrary to the hypothesis not states’ MC sales status, on slopes of distribution (p=0.391). There was a significant and large interaction effect of time and MC sales status on slopes of distribution (p≤0.001).DiscussionThese findings suggest that medical cannabis program legalization may have contributed to some states having more rapid increases in Schedule II stimulant distribution rates over time.
Probiotics supplementation to adult human small intestinal stoma microbiota causes dynamic increase in the community resistance to perturbations and nutrient utilization
Authors: Jansma Jack , Thome Nicola U. , Schwalbe Markus , Chatziioannou Anastasia Chrysovalantou , Elsayed Somayah S. , van Wezel Gilles P. , van den Abbeele Pieter , van Hemert Saskia , Aidy Sahar El 
Published: January 2023

AbstractThe gut microbiota plays a pivotal role in health and disease. The use of probiotics as microbiota-targeted therapies is a promising strategy to improve host health. However, dynamic molecular mechanisms are often not elucidated, especially when targeting the small intestinal microbiota. Here, we show that supplementation of a probiotic formula (Ecologic®825) to the adult human small intestinal ileostoma microbiota counteracts the growth ofEnterococcaceaeandEnterobacteriaceaeand reduces ethanol production, leading to major changes in nutrient utilization and resistance to perturbations. The observed alterations coincided with an initial increase in lactate production and decrease in pH by the probiotics, followed by a sharp increase in the levels of butyrate and propionate. Additionally, increased production of multipleN-acyl amino acids was detected in the stoma samples supplemented with the probiotic formula. Overall, this study shows how network theory can be used to improve the current or identify novel microbiota-targeted therapies. The outcome may help further understand the reported effects of these probiotic formula on the host.
Sex differences, asymmetry and age-related white matter development in infants and 5-year-olds as assessed with Tract-Based Spatial Statistics
Authors: Kumpulainen Venla , Merisaari Harri , Silver Eero , Copeland Anni , Pulli Elmo P. , Lewis John D , Saukko Ekaterina , Shulist Satu J. , Saunavaara Jani , Parkkola Riitta , Lähdesmäki Tuire , Karlsson Linnea , Karlsson Hasse , Tuulari Jetro J. 
Published: January 2023

ABSTRACTThe rapid white matter (WM) maturation of first years of life is followed by slower yet long-lasting development, accompanied by learning of more elaborate skills. By the age of five years, behavioural and cognitive differences between females and males, and functions associated with brain lateralization such as language skills are appearing. Diffusion tensor imaging (DTI) can be used to quantify fractional anisotropy (FA) within the WM and increasing values correspond to advancing brain development. To investigate the normal features of WM development during early childhood, we gathered a DTI data set of 166 healthy infants (mean 3.8 wk, range 2-5wk; 89 males; born on gestational week 36 or later) and 144 healthy children (mean 5.4 years, range 5.1-5.8 years; 76 males). The sex differences, lateralization patterns and age-dependent changes were examined using tractbased spatial statistics (TBSS). In 5-year-olds, females showed higher FA in wide-spread regions in the posterior and the temporal WM and more so in the right hemisphere, while sex differences were not detected in infants. Gestational age showed stronger association with FA values compared to age after birth in infants. Additionally, child age at scan associated positively with FA around the age of 5 years in the body of corpus callosum, the connections of which are important especially for sensory and motor functions. Lastly, asymmetry of WM microstructure was detected already in infants, yet significant changes in lateralization pattern seems to occur during early childhood, and in 5-year-olds the pattern already resembles adult-like WM asymmetry.HighlightsWhite matter tract integrity shows widespread sex differences at the age of 5 years.White matter structure is highly lateralized during early childhood, and changes in asymmetry occur between the birth and 5 years of age.The white matter lateralization pattern of 5-year-olds, unlike of infants, resembles asymmetry observed in adults.
Invasive Californian death caps develop mushrooms unisexually and bisexually
Authors: Wang Yen-Wen , McKeon Megan C. , Elmore Holly , Hess Jaqueline , Golan Jacob , Gage Hunter , Mao William , Harrow Lynn , Gonçalves Susana C. , Hull Christina M. , Pringle Anne 
Published: January 2023

AbstractCanonical sexual reproduction among basidiomycete fungi involves the fusion of two haploid individuals of different sexes, resulting in a heterokaryotic mycelial body made up of genetically different nuclei1. Using population genomics data, we discovered mushrooms of the deadly invasiveAmanita phalloidesare also homokaryotic, evidence of sexual reproduction by single individuals. In California, genotypes of homokaryotic mushrooms are also found in heterokaryotic mushrooms, implying nuclei of homokaryotic mycelia also promote outcrossing. We discovered death cap mating is controlled by a single mating-type locus (A. phalloidesis bipolar), but the development of homokaryotic mushrooms appears to bypass mating-type gene control. Ultimately, sporulation is enabled by nuclei able to reproduce alone as well as with others, and nuclei competent for both unisexuality and bisexuality have persisted in invaded habitats for at least 17 but potentially as long as 30 years. The diverse reproductive strategies of invasive death caps are likely facilitating its rapid spread, revealing a profound similarity between plant, animal and fungal invasions2,3.
Meta Learning Improves Robustness and Performance in Machine Learning-Guided Protein Engineering
Authors: Minot Mason , Reddy Sai T. 
Published: January 2023

AbstractMachine learning-guided protein engineering continues to rapidly progress, however, collecting large, well-labeled data sets remains time and resource intensive. Directed evolution and protein engineering studies often require extensive experimental processes to eliminate noise and fully label high-throughput protein sequence-function data. Meta learning methods established in other fields (e.g. computer vision and natural language processing) have proven effective in learning from noisy data, given the availability of a small data set with trusted labels and thus could be applied for protein engineering. Here, we generate yeast display antibody mutagenesis libraries and screen them for target antigen binding followed by deep sequencing. Meta learning approaches are able to learn under high synthetic and experimental noise as well as in under labeled data settings, typically outperforming baselines significantly and often requiring a fraction of the training data. Thus, we demonstrate meta learning may expedite and improve machine learning-guided protein engineering.Availability and implementationThe code used in this study is publicly available athttps://github.com/LSSI-ETH/meta-learning-for-protein-engineering.Graphical Abstract
How to build responsive service processes in German banks: the role of process documentation and the myth of automation
Authors: Oberle Laura Johanna 
Published: January 2023

PurposeThis multi-method paper investigates the impact factors of process responsiveness, operationalized as process duration, in the bread-and-butter business of German banks, i.e. the private mortgage loan application evaluation process. The tested predictors refer to process design, process execution, business process management (BPM)'s relevance and information technology (IT) support.Design/methodology/approachIn a sequential research design, a total of 296 useable responses of 1,228 contacted German banks are collected using a questionnaire built from both industry insights gained through 43 expert interviews and theoretical knowledge. Ordinary least squares (OLS) regression is used to determine the relevant impact factors and moderation effects, and a theoretical framework is proposed.FindingsProper process documentation moderated by bank size is most influential for process speed, and smaller banks benefit more from it. Automation appears to have a prolonging effect on the process. Although surprising, this finding may be explained through correlation analysis of the data and studies on the Solow’ paradox in the literature.Research limitations/implicationsThe models only partially explain process responsiveness. A moderate adjusted R² and several interaction effects indicate the complexity of the presented research question. Still, several hypotheses can be confirmed, leading back to the roots of process improvement and the long-lasting question of the binary impact nature of automation.Originality/valueValuable insights for both researchers in service operations and bank practitioners are outlined, shedding light onto responsiveness as still empirically under-researched operational capability. Thereby, the authors also contribute to the superior question of strategic fit.
Coolly provocative: a microfoundational framework of interorganizational cultural distance and exploratory innovation
Authors: Hui Pamsy P. , Fu Jeanne Ho-Ying , Tong Yuk-yue 
Published: January 2023

PurposeInterorganizational collaboration has been a major source of exploratory innovation. Despite much research, the authors’ understanding about how partner cultural distance is harnessed for exploratory innovation is limited. The authors’ conceptual framework aims to address this gap by explaining the social-psychological processes between perceived partner cultural distance and exploratory innovation.Design/methodology/approachDrawing on research in organizational learning and culture mixing, the authors propose a multilevel model with two parallel processes – cultural brokering and cultural defense. If managers are engaged in the former and are protected from the latter, then the partnership will produce more exploratory innovation. Cultural brokering is encouraged by prompting a learning mindset, while cultural defense is preempted by dampening social categorization across organizational boundaries.FindingsCultural brokering can be encouraged by building operational-level managers' (OLMs') collaborative strength through developing a learning orientation, allowing them delivery for exploration, cultivating mutual trust with partners. Cultural defense can be preempted by protecting OLMs from intergroup anxieties through providing organizational support to the OLMs, bridging social categorization faultlines and setting shared collaborative goals. Whether an alliance can unleash its potential depends on not just how cultural brokering is enabled but also how cultural defense is curtailed.Originality/valueThis paper takes a microfoundational approach and considers micro-level processes in a partnership. Furthermore, the model takes the operational managers' perspective and defines culture at the organizational level. All these differences allow us to provide a nuanced picture of how diverse partnerships can be harnessed for exploratory innovation through a few easily-implementable measures.