bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mortality associated with influenza and Omicron infections in France and vaccination of healthcare workers in nursing homes
Authors: Goldstein Edward 
Published: June 2023

AbstractBackgroundDuring the winter of 2022-2023, high rates of all-cause mortality, not seen since April 2020, were recorded in France, with excess all-cause mortality being related to the Omicron and influenza epidemics during that period. Moreover, that period saw a significant increase in the proportion of residents in long-term care facilities among cases of death in the population. Studies have found that increased influenza vaccination coverage in healthcare workers can result in a substantial reduction (up to 20%-30% during the course of select influenza seasons in the pre-pandemic period) in all-cause mortality in residents in nursing homes.MethodsWe applied the previously developed methodology to estimate the contribution of influenza infections to all-cause mortality in France for the 2014-2015 through the 2018-2019 influenza seasons, and the contribution of both SARS-CoV-2 and influenza infections to all-cause mortality between week 33, 2022 through week 12, 2023.ResultsFor the 2014-2015 through the 2018-2019 seasons, influenza was associated with an average of 15654 (95% CI (13013,18340)) deaths, while between week 33, 2022 through week 12, 2023, we estimated 7851 (5213,10463) influenza-associated deaths and 32607 (20794,44496) SARS-CoV-2 associated deaths. The number of SARS-CoV-2-associated deaths during the Omicron epidemic was significantly higher than the number of deaths with COVID-19 listed on the death certificate or the hospitalization record – for example, between weeks 33-52 in 2022, we estimated 23983 (15307,32620) SARS-CoV-2-associated deaths in France, compared with 12811 deaths with COVID-19 listed on the death certificate, and 8639 in-hospital deaths with COVID-19 during the same period. Examination of US mortality data suggests a significant contribution of Omicron infections to mortality for cardiac disease and mental/behavioral disorders with COVID-19 not listed on the death certificate.ConclusionsOur results suggest the need for boosting influenza vaccination coverage in different population groups (including healthcare workers, particularly nurse assistants for whom influenza vaccination coverage rates in France are low), as well as for wider use of influenza antiviral medications in influenza-related respiratory hospitalizations with different diagnoses (including pneumonia). Wider detection and treatment of Omicron infections, particularly in older individuals/persons with underlying health conditions such as cardiac disease and mental/behavioral disorders, and wider use of bivalent COVID-19 boosters would be needed in the event of the recrudescence of Omicron circulation in France.
Phosphoprotein dynamics of interacting tumor and T cells by HySic
Authors: Ibáñez-Molero Sofía , Pruijs Jinne , Atmopawiro Alisha , Wang Fujia , Altelaar Maarten , Peeper Daniel S. , Stecker Kelly E. 
Published: June 2023

AbstractFunctional interactions between cytotoxic T cells and tumor cells are central to anti-cancer immunity. Some of the proteins involved, particularly immune checkpoints expressed by T cells, serve as promising clinical targets in immunotherapy. However, our understanding of the complexity and dynamics of the interactions between tumor cells and T cells is only rudimentary. Here we present HySic (forHybrid quantification ofSILAC (Stable Isotope Labelling by Amino acids in Cell culture)-labeled interactingcells) as an innovative method to quantify protein and phosphorylation dynamics between and within physically interacting (heterotypic) cells. We show that co-cultured HLA/antigen-matched tumor and T cells engage in physical and stable interactions, allowing for in-depth HySic analysis. This method does not require physical separation of the two cell types for subsequent MS proteome and phosphoproteome measurement using label free quantification (LFQ). We demonstrate that HySic can be used to unravel proteins contributing to functional T cell:tumor cell interactions. We validated HySic with established interactions, including those mediating IFNγ signaling. Using HySic we identified the RHO/RAC/PAK1 signaling pathway to be activated upon interaction of T cells and tumor cells. Pharmacologic inhibition of PAK1 sensitized tumor cells to T cell killing. Thus, HySic is an innovative and simple method to study short-term protein signaling dynamics in physically interacting cells, which can be easily extended to other biological systems.
Novel genomic offset metrics account for local adaptation in climate suitability forecasts and inform assisted migration
Authors: Lachmuth Susanne , Capblancq Thibaut , Prakash Anoob , Keller Stephen R. , Fitzpatrick Matthew C. 
Published: June 2023

AbstractLocal adaptation is increasingly being integrated into macroecological models, offering an evolutionary perspective that has been largely missing from climate change biogeography. Genomic offsets, which quantify the disruption of existing genotype-environment associations under environmental change, are an informative landscape genomic tool that allows for the incorporation of intra-specific adaptive differentiation into forecasts of climate suitability and thus management planning. Gradient forest (GF), a method originally developed to model community turnover along environmental gradients, is now the most commonly used approach in genomic offset estimation. However, major hurdles in the application of GF-derived offsets are (1) an inability to interpret the absolute magnitude of genomic offsets in a biologically meaningful way and (2) uncertainty in how genomic offsets compare to established species-level approaches like Ecological Niche Models (ENMs).We used both ENMs and novel, genomic offset metrics derived from GF modeling of genomic variation along climatic gradients to assess the climate change vulnerability of red spruce (Picea rubens), a cool-temperate tree species endemic to eastern North America. We show how genomic offsets can be standardized relative to contemporary genomic variation across the landscape to better represent their biological significance and facilitate comparisons among studies. In three common gardens, we found a significant negative relationship between standardized genomic offsets and red spruce growth and higher explanatory power for standardized offsets than (raw) climate transfer distances.We also derived new threshold-based metrics that we term Donor and Recipient Importance and which quantify transferability of propagules between donor and recipient localities while minimizing disruption of genotype-environment associations. This approach leverages landscape genomic information to account for local adaptation when predicting climate suitability. ENMs and our novel genomic offset metrics largely agreed in forecasting drastic northward range shifts. Combining several offset-based metrics, we show that the projected northward shift of suitable climate mainly applies to populations located in the center and northern parts of the current range, whereas southern populations might be able to persistin situowing to specific local climate adaptations. The novel metrics thus yield refined, region-specific prognoses for local persistence and show how management could be improved by considering assisted migration.
Substrate availability and dietary fibre regulate metabolism of tryptophan by human gut microbes
Authors: Sinha Anurag K. , Laursen Martin F. , Brinck Julius E. , Rybtke Morten L. , Pedersen Mikael , Roager Henrik M. , Licht Tine R. 
Published: June 2023

AbstractTryptophan is catabolized by gut microbes, resulting in a wide range of metabolites implicated in both beneficial and adverse host effects. However, it remains elusive how the gut microbial tryptophan metabolism is governed either towards indole, associated with adverse effects in chronic kidney disease, or towards indolelactic acid (ILA) and indolepropionic acid (IPA), associated with protective effects in type 2 diabetes and inflammatory bowel disease. Here, we used human fecal cultures in combination with a controlled three-species model to test competition for tryptophan, and measured the resulting metabolites bothin vitroand in gnotobiotic mice colonized with the three species. We revealed that the generation of specific tryptophan-derived metabolites was not predominantly determined by the abundance of tryptophan metabolizing bacteria, but rather by substrate-dependent regulation of specific metabolic pathways.In vitroandin vivo, indole-producingEscherichia coliand ILA- and IPA-producingClostridium sporogenescompeted for tryptophan. Importantly, the fibre degradingBacteroides thetaiotaomicronaffected this competition by cross-feeding monosaccharides toE. coli, which inhibited indole production through catabolite repression, and thereby made more tryptophan available toC. sporogenes, increasing ILA and IPA production. We thus present the first mechanistic explanation for why consumption of fermentable fibres suppress indole production but promote the generation of other tryptophan metabolites associated with health benefits. We conclude that the availability of tryptophan and dietary fibre regulates gut microbiome tryptophan metabolism pathways, and consequently influences the balance between the different tryptophan catabolites generated. This balance has implications for host-microbial cross-talk affecting human health.
Expanding the toolbox of probioticEscherichia coliNissle 1917 for synthetic biology
Authors: Ba Fang , Zhang Yufei , Ji Xiangyang , Liu Wan-Qiu , Ling Shengjie , Li Jian 
Published: June 2023

AbstractEscherichia coliNissle 1917 (EcN) is a probiotic microbe that has the potential to be developed as a promising chassis for synthetic biology applications. However, the molecular tools and techniques for utilizing EcN have not been fully explored. To address this opportunity, we systematically expanded the EcN-based toolbox, enabling EcN as a powerful platform for more applications. First, two EcN cryptic plasmids and other compatible plasmids were genetically engineered to enrich the manipulable plasmid toolbox for multiple gene coexpression. Next, we developed two EcN-based enabling technologies, including the conjugation strategy for DNA transfer, and quantification of protein expression capability. Finally, we expanded the EcN-based applications by developing EcN native integrase-mediated genetic engineering capabilities and establishing anin vitrocell-free protein synthesis (CFPS) system. Overall, this study expanded the toolbox for manipulating EcN as a commonly used probiotic chassis, providing several simplified, dependable, and predictable strategies for researchers working in synthetic biology fields.For Table of Contents Use Only
Identification of domains inPlasmodium falciparumproteins of unknown function using DALI search on Alphafold predictions
Authors: Behrens Hannah Michaela , Spielmann Tobias 
Published: June 2023

AbstractPlasmodium falciparum, the causative agent of malaria, poses a significant global health challenge, yet much of its biology remains elusive. A third of the genes in theP. falciparumgenome lack annotations regarding their function, impeding our understanding of the parasite’s biology. In this study, we employed structure predictions and the DALI search algorithm to analyse proteins encoded by uncharacterized genes in the reference strain 3D7 ofP. falciparum.By comparing Alphafold predictions to experimentally determined protein structures in the Protein Data Bank, we found similarities to known domains in 353 proteins of unknown function, shedding light on their potential functions. The lowest-scoring 5% of similarities were additionally validated using the size-independent TM-align algorithm, confirming the detected similarities in 88% of the cases. Notably, in over 70P. falciparumproteins the presence of domains resembling heptatricopeptide repeats, which are typically involvement in RNA binding and processing, was detected. This suggests this family, which is important in transcription in mitochondria and apicoplasts, is much larger inPlasmodiumparasites than previously thought. The results of this domain search provide a resource to the malaria research community that is expected to inform and enable experimental studies.
Design and assembly of the 117-kbPhaeodactylum tricornutumchloroplast genome
Authors: Walker Emma J.L. , Pampuch Mark , Chang Nelson , Cochrane Ryan R. , Karas Bogumil J. 
Published: June 2023

ABSTRACTThere is a growing impetus to expand the repository of chassis available to synthetic biologists. The chloroplast genome presents a unique chassis for engineering photosynthetic eukaryotes by virtue of its compact size, lack of epigenetic regulation, and containment within the secluded lipid bilayers of the organelle. The development of the chloroplast as a synthetic biology chassis, however, has been limited by a lack of efficient techniques for whole genome cloning and engineering. Here, we demonstrate two approaches for cloning the 117 kbPhaeodactylum tricornutumchloroplast genome that have 90 to 100% efficiency when screening as few as tenSaccharomyces cerevisiaecolonies following yeast assembly. The first method directly uses PCR-amplified fragments of the genome for yeast assembly, whereas the second method relies upon the pre-cloning of eight overlapping genomic regions into individual plasmids that they can later be released from. The cloned genome can be stably maintained and propagated withinEscherichia coli, which provides an exciting opportunity for engineering a novel delivery mechanism for bringing DNA directly to the algal chloroplast. As well, one of the cloned genomes was designed to contain a singleSapI site within the yeastURA3open-reading frame, which can be used to linearize the genome and integrate designer cassettes via golden-gate cloning or further iterations of yeast assembly.
Expanded diversity of novel hemoplasmas in rare and undersampled Neotropical bats
Authors: Volokhov Dmitriy V. , Lock Lauren R. , Dyer Kristin E. , DeAnglis Isabella K. , Andrews Benjamin R. , Simonis Molly C. , Stockmaier Sebastian , Carter Gerald G. , Downs Cynthia J. , Fenton M. Brock , Simmons Nancy B. , Becker Daniel J. 
Published: June 2023

AbstractHemotropic mycoplasmas are emerging as a model system for studying bacterial pathogens in bats, but taxonomic coverage of sampled host species remains biased. We leveraged a long-term field study in Belize to uncover novel hemoplasma diversity in bats by analyzing 80 samples from 19 species, most of which are infrequently encountered. PCR targeting the partial 16S rRNA gene found 41% of bats positive for hemoplasmas. Phylogenetic analyses found two novel host shifts of hemoplasmas, four entirely new hemoplasma genotypes, and the first hemoplasma detections in four bat species. One of these novel hemoplasmas (fromNeoeptesicus furinalis) shared 97.6% identity in the partial 16S rRNA gene to a human hemoplasma (CandidatusMycoplasma haemohominis). Additional analysis of the partial 23S rRNA gene allowed us to also designate two novel hemoplasma species, inMyotis elegansandPhyllostomus discolor, with the proposed namesCandidatusMycoplasma haematomyotis sp. nov. andCandidatusMycoplasma haematophyllostomi sp. nov., respectively. Our analyses show that additional hemoplasma diversity in bats can be uncovered by targeting rare or undersampled host species.
Emerging costs in a “hidden” workforce: The longitudinal psychosocial effects of caregiving during the COVID-19 pandemic among Norwegian adults
Authors: Hansen Thomas , Hynek Kamila , McMunn Anne , Nes Ragnhild Bang , Skirbekk Vegard , Vollrath Margarethe , Methi Fredrik 
Published: June 2023

AbstractDuring COVID-19 many informal caregivers experienced increased caregiving load while access to formal and informal support systems and coping resources decreased. Little is known about the psychosocial costs of these challenges for an essential yet vulnerable and “hidden” frontline workforce. This study explores and compares changes in psychosocial well-being (psychological well-being, psychological ill-being, and loneliness) before and across up to three stages of the COVID-19 pandemic among caregivers and non-caregivers. We also examine predictors of psychosocial well-being among caregivers during the peak of the pandemic. We use longitudinal data collected online in the Norwegian Counties Public Health Survey (age 18–92) in four countries and up to four data points (n=14,881). Caregivers are those who provide care unpaid, continuous (≥ monthly across all time points) help to someone with health problems. Findings show that levels of psychosocial well-being first remained stable but later, during the peak stages of the pandemic, dropped markedly. Caregivers (13−15% of the samples) report lower psychosocial well-being than non-caregivers both before and during the pandemic. Caregivers seem especially vulnerable in terms of ill-being, and during the peak of the pandemic caregivers report higher net levels of worry (OR = 1.22, p< .01) and anxiety (OR = 1.23, p< .01) than non-caregivers. As expected, impacts are graver for caregivers who provide more intensive care and those reporting health problems or poor access to social support. Our study findings are valuable information for interventions to support caregivers during this and future pandemics.
Cortical circuitry mediating inter-areal touch signal amplification
Authors: Ryan Lauren , Sun-Yan Andrew , Laughton Maya , Peron Simon 
Published: June 2023

AbstractSensory cortical areas are often organized into topographic maps which represent the sensory epithelium1,2. Individual areas are richly interconnected3, in many cases via reciprocal projections that respect the topography of the underlying map4,5. Because topographically matched cortical patches process the same stimulus, their interaction is likely central to many neural computations6-10. Here, we ask how topographically matched subregions of primary and secondary vibrissal somatosensory cortices (vS1 and vS2) interact during whisker touch. In the mouse, whisker touch-responsive neurons are topographically organized in both vS1 and vS2. Both areas receive thalamic touch input and are topographically interconnected4. Volumetric calcium imaging in mice actively palpating an object with two whiskers revealed a sparse population of highly active, broadly tuned touch neurons responsive to both whiskers. These neurons were especially pronounced in superficial layer 2 in both areas. Despite their rarity, these neurons served as the main conduits of touch-evoked activity between vS1 and vS2 and exhibited elevated synchrony. Focal lesions of the whisker touch-responsive region in vS1 or vS2 degraded touch responses in the unlesioned area, with whisker-specific vS1 lesions degrading whisker-specific vS2 touch responses. Thus, a sparse and superficial population of broadly tuned touch neurons recurrently amplifies touch responses across vS1 and vS2.
Can the “Current View” show that autistic young people referred to mental health services have more comorbidities and complex needs?
Authors: Thompson Lisa Marie , Wilkinson Ewan , Nall-Evans Sharleen , Michelet Felix , Lewis Michael Thomas , Pender Fiona , Jaydeokar Sujeet 
Published: June 2023

Purpose
Autistic young people have health and care needs that may benefit from a multi-agency intervention. The “Current View” tool is routinely used in England to profile the needs of young people referred to mental health services. This study aims to examine associations between comorbidities and complex needs in autistic and non-autistic young people to assess the multifaceted needs of autistic young people.

Design/methodology/approach
A cohort study was conducted using data from the electronic patient record, comparing autistic and non-autistic young people to see which items in the four “Current View” tool categories were associated with autistic young people.

Findings
Issues associated with autistic young people were: “community issues”, “attainment issues” and “deemed child in need” (all p < 0.001). Autistic young people scored significantly more items (p < 0.05) in the categories complexity/contextual/educational factors. Comorbidities associated with autistic young people included anxiety, “behavioural difficulties”, “peer relationship difficulties” and “self-care issues” (all p < 0.001). There was an association with increased comorbidities and complexity factors in autistic young people which suggests increased support from agencies may be beneficial.

Originality/value
Few studies have used data in the “Current View” tool to assess young people referred to services. More use could be made of this data for planning and delivering services.
Which sustainable growth rate is best at forecasting actual growth?
Authors: Moore Gary , Simpson Marc William 
Published: June 2023

PurposeUsing various proxies for the firms' return on equity (ROE) and retention ratios (b) the authors calculate 36 sustainable growth rates, on a rolling basis, for a comprehensive set of firms over a 52-year period. The authors then assess the ability of these different sustainable growth rates to predict the actual, out-of-sample, five-year growth rates of the firms' earnings.Design/methodology/approachThe authors compare the forecast to determine which method of estimating ROE and b produce the lowest mean-squared-errors and then determine the estimation method that works best for firms with different characteristics and for firms in different industries.FindingsOverall, using the median ROE of all firms in the market and the 5-year average of the specific firm's retention ratio produces the lowest, statistically significant, forecast errors. Variations are documented based on firm characteristics, including dividend payout, level of ROE and industry.Practical implicationsThe findings can guide practitioners in using the best earnings forecasting method.Originality/valueFinancial textbooks seem universally to suggest that one method of estimating the growth rate of a firm's earnings is to calculate the “sustainable growth rate” by multiplying the firm's ROE by the firm's b. At the same time, multiple methods of proxying for both ROE and b have been suggested; therefore, it is an interesting and useful empirical question, which, heretofore, has not been addressed in the literature, as to which estimation of the sustainable growth rate best approximates the actual future growth of the firm's earnings. The findings can guide practitioners in using the best earnings forecasting method.