bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Presence of the Temporal Horn Exacerbates the Vulnerability of Hippocampus during Head Impacts
Authors: Zhou Zhou , Li Xiaogai , Domel August G , Dennis Emily L , Georgiadis Marios , Liu Yuzhe , Raymond Samuel J. , Grant Gerald , Kleiven Svein , Camarillo David , Zeineh Michael 
Published: December 2021

AbstractHippocampal injury is common in traumatic brain injury (TBI) patients, but the underlying pathogenesis remains elusive. In this study, we hypothesize that the presence of the adjacent fluid-containing temporal horn exacerbates the biomechanical vulnerability of the hippocampus. Two finite element models of the human head were used to investigate this hypothesis, one with and one without the temporal horn, and both including a detailed hippocampal subfield delineation. A fluid-structure interaction coupling approach was used to simulate the brain-ventricle interface, in which the intraventricular cerebrospinal fluid was represented by an arbitrary Lagrangian-Eulerian multi-material formation to account for its fluid behavior. By comparing the response of these two models under identical loadings, the model that included the temporal horn predicted increased magnitudes of strain and strain rate in the hippocampus with respect to its counterpart without the temporal horn. This specifically affected cornu ammonis (CA) 1 (CA1), CA2/3, hippocampal tail, subiculum, and the adjacent amygdala and ventral diencephalon. These computational results suggest that the presence of the temporal horn exacerbate the vulnerability of the hippocampus, highlighting the mechanobiological dependency of the hippocampus on the temporal horn.
Staffing levels and hospital mortality in England: a national panel study using routinely collected data
Authors: Rubbo Bruna , Saville Christina , Dall’Ora Chiara , Turner Lesley , Jones Jeremy , Ball Jane , Culliford David , Griffiths Peter 
Published: December 2021

AbstractBackgroundMost studies investigating the association between hospital staff levels and mortality have focused on single professional groups, in particular nursing. However, single staff group studies might overestimate effects or neglect important contributions to patient safety from other staff groups. We aimed to examine the association between multiple clinical staff levels and case-mix adjusted patient mortality in English hospitals.Methods and FindingsThis retrospective observational study used routinely available data from all 138 National Health Service hospital trusts that provided general acute adult services in England between 2015 and 2019. Standardised mortality rates were derived from the Summary Hospital level Mortality Indicator dataset. Estimates for the effect of clinical staffing from the single staff models were generally higher than estimates from models with multiple staff groups. Using a multilevel negative binomial random effects model, hospitals with higher levels of medical and allied healthcare professional (AHP) staff had significantly lower mortality rates (1.04, 95%CI 1.02 to 1.06, and 1.04, 95%CI 1.02 to 1.06, respectively), while those with higher support staff had higher mortality rates (0.85, 95%CI 0.79 to 0.91 for nurse support, and 1.00, 95%CI 0.99 to 1.00 for AHP support), after adjusting for multiple staff groups and hospital characteristics. Estimates of staffing levels on mortality were higher in magnitude between- than within-hospitals, which were not statistically significant in a within-between random effects model.ConclusionsWe showed the importance of considering multiple staff groups simultaneously when examining the association between hospital mortality and clinical staffing levels. Despite not being included in previous workforce studies, AHP and AHP support levels have a significant impact on hospital mortality. As the main variation was seen between-as opposed to within-hospitals, structural recruitment and retention difficulties coupled with financial constraints could contribute to the effect of staffing levels on hospital mortality.
Safety and Immunogenicity of SARS-CoV-2 S-2P Protein Vaccine MVC-COV1901 in People Living with HIV
Authors: Cheng Shu-Hsing , Lien Chia En , Hsieh Szu-Min , Cheng Chien-Yu , Liu Wang-Da , Lo Ching-Lung , Ko Wen-Chien , Chen Yen-Hsu , Huang Ching-Tai , Chang Hsiao-Ting , Hwang Shinn-Jang , Wang Ning-Chi , Liu Ming-Che , Lee Yu-Lin , Tai I-Chen , Garcia Estrada Josue Antonio , Lin Tzou-Yien , Lee Wen-Sen 
Published: December 2021

AbstractObjectivesTo provide data on the immune response to COVID-19 vaccines in people living with HIV (PWH), MVC-COV1901, a recombinant protein vaccine containing S-2P protein adjuvanted with CpG 1018 and aluminium hydroxide, was assessed.MethodsA total of 57 PWH of ≥ 20 years of age who are on stable antiretroviral therapy and with CD4+ T cell ≥ 350 cells/mm3 and HIV viral load < 103 copies/ml were compared with 882 HIV-negative participants. Participants received 2 doses of MVC-COV1901 28 days apart. Safety and the immunogenicity were evaluated.ResultsNo vaccine-related serious adverse events (SAEs) were recorded. Seroconversion rates (SCRs) of 100% and 99.8% were achieved in people living with HIV (PWH) and comparators, respectively, 28 days after second dose. The geometric mean titers (GMTs) (95% confidence interval [CI]) against wild type SARS-CoV-2 virus were 136.62 IU/mL (WHO Standardized International Unit) (95% CI 114.3-163.3) and 440.41 IU/mL (95% CI 421.3-460.4), for PWH and control groups, respectively, after adjusting for sex, age, BMI category, and comorbidity, and the adjusted GMT ratio of comparator/PWH was 3.22 (95% CI 2.6-4.1). A higher CD4/CD8 ratio was associated with a higher GMT (R=0.27, p=0.039).ConclusionsMVC-COV1901 has shown robust safety but weaker immunogenicity responses in PWH. As a result, a third dose or booster doses of MVC-COV1901 may be appropriate for PWH.
The spread of SARS-CoV-2 variant Omicron with the doubling time of 2.0–3.3 days can be explained by immune evasion
Authors: Grabowski Frederic , Kochańczyk Marek , Lipniacki Tomasz 
Published: December 2021

AbstractOmicron, the novel highly mutated SARS-CoV-2 Variant of Concern (VOC, Pango lineage B.1.1.529), was first collected in early November 2021 in South Africa. By the end of November 2021, it had spread and approached fixation in South Africa, and had been detected on all continents. We analyzed the exponential growth of Omicron over the four-week periods in two most populated South Africa’s provinces, Gauteng and KwaZulu-Natal, arriving at the doubling time estimates of respectively 3.3 days [95% CI: 3.2–3.4 days] and 2.7 days [95% CI: 2.3–3.3 days]. Similar or even shorter doubling times were observed in other locations: Australia (3.0 days), New York State (2.5 days), UK (2.4 days), and Denmark (2.0 days). Log– linear regression suggests that the spread began in Gauteng around October 11, 2021, however, due to presumable stochasticity in the initial spread, this estimate can be inaccurate. Phylogenetics-based analysis indicates that the Omicron strain started to diverge in between October 6 and October 29, 2021. We estimated that the weekly growth of the ratio of Omicron to Delta is in the range 7.2–10.2, considerably higher than the growth of the ratio of Delta to Alpha (estimated to be in in the range 2.5–4.2), and Alpha to pre-existing strains (estimated to be in the range of 1.8–2.7). High relative growth does not necessarily imply higher Omicron infectivity. A two-strain SEIR model suggests that the growth advantage of Omicron may stem from immune evasion, which permits this VOC to infect both the recovered and the fully vaccinated individuals. As we demonstrated within the model, immune evasion is more concerning than increased transmissibility, because it can facilitate larger epidemic outbreaks.
Vaccinating Children Against COVID-19 is Essential Prior to the Removal of Non-Pharmaceutical Interventions
Authors: Rosenstrom Erik , Mele Jessica , Ivy Julie , Mayorga Maria , Patel Mehul , Lich Kristen Hassmiller , Delamater Paul , Smith Raymond , Swann Julie L. 
Published: December 2021

AbstractObjectives(s)To evaluate the joint impact of childhood vaccination rates and masking policies, in schools and workplaces, on community transmission and severe outcomes due to COVID-19.Study designWe utilized a stochastic, agent-based simulation of North Carolina, to evaluate the impact of 24 health policy decisions on overall incidence of disease, COVID-19 related hospitalization, and mortality from July 1, 2021-July 1, 2023.ResultsUniversal mask removal in schools in January 2022 could lead to a 38.1-47%, 27.6-36.2%, and 15.9-19.7% increase in cumulative infections for ages 5-9, 10-19, and the total population, respectively, depending on the rate of vaccination of children relative to the adult population. Additionally, without increased vaccination uptake in the adult population, a 25% increase in child vaccination uptake from 50% to 75% uptake and from 75% to 100% uptake relative to the adult population, leads to a 22% and 18% or 28% and 33% decrease in peak hospitalizations in 2022 across scenarios when masks are removed either January 1st or March 8th 2022, respectively. Increasing vaccination uptake for the entire eligible population can reduce peak hospitalizations in 2022 by an average of 89% and 92% across all masking scenarios compared to the scenarios where no children are vaccinated.Conclusion(s)High vaccination uptake among both children and adults is necessary to mitigate the increase in infections from mask removal in schools and workplaces.
Harnessing gene-gene interactions via an RNA-Sequencing network analysis framework improves precision medicine prediction in rheumatoid arthritis
Authors: Sciacca Elisabetta , Surace Anna E. A. , Alaimo Salvatore , Pulvirenti Alfredo , Rivellese Felice , Goldmann Katriona , Ferro Alfredo , Latora Vito , Pitzalis Costantino , Lewis Myles J. 
Published: December 2021

ABSTRACTThe study of gene-gene interactions in RNA-Sequencing (RNA-Seq) data has traditionally been hard owing the large number of genes detectable by Next-Generation Sequencing (NGS). However, differential gene-gene pairs can inform our understanding of biological processes and yield improved prediction models. Here, we utilised four well curated pathway repositories obtaining 10,537 experimentally evaluated gene-gene interactions. We then extracted specific gene-gene interaction networks in synovial RNA-Seq to characterise histologically-defined pathotypes in early rheumatoid arthritis patients. Specific gene-gene networks were also leveraged to predict response to methotrexate-based disease-modifying anti-rheumatic drug (DMARD) therapy in the Pathobiology of Early Arthritis Cohort (PEAC). We statistically evaluated the differential interactions identified within each network using robust linear regression models, and the ability to predict response was evaluated by receiver operating characteristic (ROC) curve analysis.The analysis comparing different histological pathotypes showed a coherent molecular signature matching the histological changes and highlighting novel pathotype-specific gene interactions and mechanisms. Analysis of responders vs non-responders revealed higher expression of apoptosis regulating gene-gene interactions in patients with good response to conventional synthetic DMARD. Detailed analysis of interactions between pairs of network-linked genes identified the SOCS2/STAT2 ratio as predictive of treatment success, improving ROC area under curve (AUC) from 0.62 to 0.78. In conclusions, we demonstrate a novel, powerful method which harnesses gene interaction networks for leveraging biologically relevant gene-gene interactions leading to improved models for predicting treatment response.
Ancient DNA from a 2,700-year-old goitered gazelle (Gazella subgutturosa) confirms gazelle hunting in Iron Age Central Asia
Authors: Rodrigues Soares André Elias , Boroffka Nikolaus , Schröder Oskar , Sverchkov Leonid , Benecke Norbert , Günther Torsten 
Published: December 2021

AbstractCentral Asia has been an important region connecting the different parts of Eurasia throughout history and prehistory, with large states developing in this region during the Iron Age. Archaeogenomics is a powerful addition to the zooarchaeological toolkit for understanding the relation of these societies to animals. Here, we present the genetic identification of a goitered gazelle specimen (Gazella subgutturosa) at the site Gazimulla-Tepa, in modern-day Uzbekistan, confirming hunting of the species in the region during the Iron Age. The sample was directly radiocarbon dated to 2724-2439 calBP. A phylogenetic analysis of the mitochondrial genome places the individual into the modern variation of G. subgutturosa. Our data does represent both the first ancient DNA and the first nuclear DNA sequences of this species. The lack of genomic resources available for this gazelle and related species prevented us from performing a more in-depth analysis of the nuclear sequences generated. Therefore, we are making our sequence data available to the research community to facilitate other research of this nowadays threatened species which has been subject to human hunting for several millennia across its entire range on the Asian continent.
The UV RESISTANCE LOCUS 8-Mediated UV-B Response Is Required Alongside CRYPTOCHROME1 For Plant Survival Under Sunlight In The Field
Authors: Stockenhuber Reinhold , Akiyama Reiko , Tissot Nicolas , Yamazaki Misako , Wyler Michele , Arongaus Adriana B. , Podolec Roman , Sato Yasuhiro , Milosavljevic Stefan , Widmer Alex , Ulm Roman , Shimizu Kentaro K. 
Published: December 2021

AbstractAs sessile organisms, plants are subjected to fluctuating sunlight including potentially detrimental ultraviolet-B radiation (UV-B). In Arabidopsis thaliana, experiments under controlled conditions have shown that UV RESISTANCE LOCUS 8 (UVR8) controls photomorphogenic responses for acclimation and tolerance to UV-B; however, its long-term impacts on plant performance remain poorly understood in naturally fluctuating environments. Here we quantified the survival and reproduction of different Arabidopsis mutant genotypes in diverse field and laboratory conditions. We found that uvr8 mutants produced more fruits than wild type in growth chambers with artificial low UV-B conditions but not in natural field conditions. Importantly, independent double mutants of UVR8 and the blue-light photoreceptor gene CRYPTOCHROME 1 (CRY1) in two genetic backgrounds showed a drastic reduction in fitness in the field. UV-B attenuation experiments in field conditions and supplemental UV-B in growth chambers demonstrated that UV-B caused the conditional cry1 uvr8 lethality phenotype. RNA sequencing in different conditions revealed a large number of genes with statistical interaction of UVR8 and CRY1 mutations in the presence of UV-B in the field. Among them, Gene Ontology analysis identified enrichment of categories related to UV-B response, oxidative stress, photoprotection and DNA damage repair. Our study demonstrates the functional importance of the UVR8-mediated response across life stages in natura, which is partially redundant with CRY1, and provides an integral picture of gene expression associated with plant environmental responses under diverse environmental conditions.
Rewarded extinction increases amygdalar connectivity and stabilizes long-term memory traces in the vmPFC
Authors: Keller Nicole E. , Hennings Augustin C. , Leiker Emily K. , Lewis-Peacock Jarrod A. , Dunsmoor Joseph E. 
Published: December 2021

AbstractNeurobiological evidence in rodents indicates that threat extinction incorporates reward neurocircuitry. Consequently, incorporating reward associations with an extinction memory may be an effective strategy to persistently attenuate threat responses. Moreover, while there is considerable research on the short-term effects of extinction strategies in humans, the long-term effects of extinction are rarely considered. In a within-subjects fMRI study, we compared counterconditioning (a form of rewarded-extinction) to standard extinction, at recent (24 hours) and remote (∼1 month) retrieval tests. Relative to standard extinction, counterconditioning diminished 24-hour relapse of arousal and threat expectancy, and reduced activity in brain regions associated with the appraisal and expression of threat (e.g., thalamus, insula, periaqueductal gray). The retrieval of reward-associated extinction memory was accompanied by functional connectivity between the amygdala and the ventral striatum, whereas the retrieval of standard-extinction memories was associated with connectivity between the amygdala and ventromedial prefrontal cortex (vmPFC). One-month later, the retrieval of both standard- and rewarded-extinction was associated with amygdala-vmPFC connectivity. However, only rewarded extinction created a stable memory trace in the vmPFC, identified through overlapping multivariate patterns of fMRI activity from extinction to 24-hour and 1-month retrieval. These findings provide new evidence that reward may generate a more stable and enduring memory trace of attenuated threat in humans.Significance StatementPrevalent treatments for pathological fear and anxiety are based on the principles of Pavlovian extinction. Unfortunately, extinction forms weak memories that only temporarily inhibit the retrieval of threat associations. Thus, to increase the translational relevance of extinction research, it is critical to investigate whether extinction can be augmented to form a more enduring memory, especially after long intervals. Here, we used a multi-day fMRI paradigm in humans to compare the short- and long-term neurobehavioral effects of aversive-to-appetitive counterconditioning, a form of augmented extinction. Our results provide novel evidence that including an appetitive stimulus during extinction can reduce short-term threat relapse and stabilize the memory trace of extinction in the vmPFC, for at least one month after learning.
An Engineered Nanocomplex with Photodynamic and Photothermal Synergistic Properties for Cancer Treatment
Authors: Varon Eli , Blumrosen Gaddi , Sinvani Moshe , Haimov Elina , Polani Shlomi , Natan Michal , Shoval Irit , Jacob Avi , Atkins Ayelet , Zitoun David , Shefi Orit 
Published: December 2021

AbstractPhotodynamic therapy (PDT) and photothermal therapy (PTT) are promising therapeutic methods for cancer treatment; however, as single modality therapies, either PDT or PTT are still limited in their success rate. A dual application of both PDT and PTT, in a combined protocol, has gained immense interest. In this study, gold nanoparticles (AuNPs) are conjugated with a PDT agent, meso-tetrahydroxyphenylchlorin (mTHPC) photosensitizer, designed as nanotherapeutic agents that can activate a dual photodynamic/photothermal therapy.The AuNP-mTHPC complex is biocompatible, soluable, and photostable. PDT efficiency is high because of immediate reactive oxygen species (ROS) production upon mTHPC activation by the 650 nm laser which decreased mitochondrial membrane potential (ΔΨm). Likewise, the AuNP-mTHPC complex is used as a photoabsorbing (PTA) agent for PTT, due to efficient plasmon absorption and excellent photothermal conversion characteristics of AuNPs under laser irradiation at 532 nm. Under the laser irradiation of a PDT/PTT combination, a twofold phototoxicity outcome follows, compared to PDT-only or PTT-only treatment. This indicates that PDT and PTT have synergistic effects together as a combined therapeutic method. Hence, applying our AuNP-mTHPC may be a potential treatment of cancer in the biomedical field.Abstract Figure
Wanted not, wasted not: Searching for non-target taxa in environmental DNA metabarcoding by-catch
Authors: Ritter Camila Duarte , Pont Giorgi Dal , Stika Paula Valeska , Horodesky Aline , Cozer Nathieli , Mader Netto Otto Samuel , Henn Caroline , Ostrensky Antonio , Pie Marcio R. 
Published: December 2021

AbstractMetabarcoding of environmental DNA is based on primers that are specific to the target taxa (e.g. bacteria, zooplankton, fishes). However, due to the nature of the commonly used protocols, regardless of the chosen primers, several sequences of non-target species will inevitably be generated, but are usually discarded in commonly used bioinformatics pipelines. These non-target sequences might contain important biological information about the presence of other species in the studied habitats and its potential for ecological studies is still poorly understood. Here, we analyzed the presence of mammal and bird species in aquatic environmental samples that were originally amplified targeting teleost fish species. After all cleaning and checking steps, we kept 21 amplicon sequence variants (ASVs) belonging to mammals and ten to birds. Most ASVs were taxonomic assigned to farm/domestic animals, such as cats, cows, and ducks. Yet, we were able to identify a native semi-aquatic mammal, the capybara, in the samples. Four native bird species and a non-native potentially invasive bird (Corvussp.) were also detected. Although the data derived from these samples for mammals and birds are of limited use for diversity analyses, our results demonstrate the potential of aquatic samples to characterize non-aquatic birds and highlight the presence of a potentially invasive species that had not been recorded before in the region.
Canalized morphogenesis driven by inherited tissue asymmetries in Hydra regeneration
Authors: Shani-Zerbib Lital , Garion Liora , Maroudas-Sacks Yonit , Braun Erez , Keren Kinneret 
Published: December 2021

AbstractThe emergence and stabilization of a body axis is a major step in animal morphogenesis, determining the symmetry of the body plan as well as its polarity. To advance our understanding of the emergence of body-axis polarity we study regenerating Hydra. Axis polarity is strongly memorized in Hydra regeneration even in small tissue segments. What type of processes confer this memory? To gain insight into the emerging polarity, we utilize frustrating initial conditions by studying regenerating tissue strips which fold into hollow spheroids by adhering their distal ends, of opposite original polarities. Despite the convoluted folding process and the tissue rearrangements during regeneration, these tissue strips develop a new organizer in a reproducible location preserving the original polarity and yielding an ordered body plan. These observations suggest that the integration of mechanical and biochemical processes supported by their mutual feedback attracts the tissue dynamics towards a well-defined developmental trajectory biased by weak inherited cues from the parent animal. Hydra thus provide an example of dynamic canalization in which the dynamic rules themselves are inherited, in contrast to the classical picture where a detailed developmental trajectory is pre-determined.