bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of food on capsule and granule formulations of selumetinib
Authors: Cohen‐Rabbie Sarit , Mattinson Alexandra , So Karen , Wang Nan , Goldwater Ronald
Published: February 2022

Selumetinib is an oral, potent, and highly selective allosteric MEK1/2 inhibitor approved for the treatment of pediatric patients (aged ≥2 years) with neurofibromatosis type 1 who have symptomatic, inoperable plexiform neurofibromas. A granule formulation of selumetinib is under development to improve dosing precision for younger pediatric patients who may be unable to swallow capsules. This phase I crossover study investigated the effect of food on the pharmacokinetic (PK) properties of selumetinib capsule and granule formulations. Healthy male volunteers were randomized to receive selumetinib granules (25 mg) or capsules (50 mg [2 × 25 mg]) under fasted or fed conditions (a low‐fat meal). Plasma concentrations and PK parameters were determined less than or equal to 48 h postdose. Safety and tolerability were assessed. Across 24 volunteers, selumetinib was absorbed quickly, with a time to maximum concentration (Tmax) ranging from ~1–3 h. Geometric mean ratios (90% confidence interval [CI]) for maximum plasma concentration (Cmax) in the fed versus fasted state were 0.61 (90% CI 0.51–0.72) and 0.40 (90% CI 0.33–0.48) for the granule and capsule formulations, respectively, whereas geometric mean ratios (90% CI) for area under the plasma drug concentration‐time curve in the fed versus fasted state were 0.97 (90% CI 0.91–1.02) and 0.62 (90% CI 0.55–0.70), respectively. Levels of less than 10% conversion to the N‐desmethyl selumetinib metabolite were observed. Selumetinib was well‐tolerated, with only a few adverse events of mild intensity reported. Selumetinib administration with a low‐fat meal resulted in lower Cmax and longer Tmax for both formulations versus fasted conditions. However, area under the curve for selumetinib granules was similar under fasted and fed conditions. Overall, these findings support further development of this formulation for pediatric patients.
Pharmacokinetic equations versus Bayesian guided vancomycin monitoring: Pharmacokinetic model and model‐informed precision dosing trial simulations
Authors: Aljutayli Abdullah , Thirion Daniel J. G. , Bonnefois Guillaume , Nekka Fahima
Published: February 2022

The recently released revised vancomycin consensus guideline endorsed area under the concentration‐time curve (AUC) guided monitoring. Means to AUC‐guided monitoring include pharmacokinetic (PK) equations and Bayesian software programs, with the latter approach being preferable. We aimed to evaluate the predictive performance of these two methods when monitoring using troughs or peaks and troughs at varying single or mixed dosing intervals (DIs), and evaluate the significance of satisfying underlying assumptions of steady‐state and model transferability. Methods included developing a vancomycin population PK model and conducting model‐informed precision dosing clinical trial simulations. A one‐compartment PK model with linear elimination, exponential between‐subject variability, and mixed (additive and proportional) residual error model resulted in the best model fit. Conducted simulations demonstrated that Bayesian‐guided AUC can, potentially, outperform that of equation‐based AUC predictions depending on the quality of model diagnostics and met assumptions. Ideally, Bayesian‐guided AUC predictive performance using a trough from the first DI was equivalent to that of PK equations using two measurements (peak and trough) from the fifth DI. Model transferability diagnostics can guide the selection of Bayesian priors but are not strong indicators of predictive performance. Mixed versus single fourth and/or fifth DI sampling seems indifferent. This study illustrated cases associated with the most reliable AUC predictions and showed that only proper Bayesian‐guided monitoring is always faster and more reliable than equations‐guided monitoring in pre‐steady‐state DIs in the absence of a loading dose. This supports rapid Bayesian monitoring using data as sparse and early as a trough at the first DI.
The endangered freshwater pearl mussel Margaritifera margaritifera shows adaptation to a local salmonid host in Finland
Authors: Taskinen Jouni , Salonen Jouni K.
Published: February 2022

The freshwater pearl mussel Margaritifera margaritifera (FPM) is an endangered unionid which has a glochidium larva that attaches to the gills of Atlantic salmon Salmo salar or brown trout S. trutta, although some FPM populations have been shown to exclusively attach to only one of these species. The origin of host fish populations may be crucial for conservation actions for this mussel species, but the relative suitability of local (sympatric) and non‐local (allopatric) salmonid populations as the hosts for FPM has been studied only rarely. We hypothesised that FPM glochidia would show adaptation to local salmonid strains and, therefore, that they would be more successful (abundant, larger) attached to sympatric than to allopatric fish.

Here, we investigated the infection success (abundance and growth of encysted larvae in fish) of FPM in local versus non‐local fish by caging different strains of brown trout and Atlantic salmon in rivers where FPM populations are present.

Higher abundances of glochidia in local fish were observed in three brown trout streams, and larger glochidia were found in sympatric hosts in one brown trout stream and in one salmon river. Furthermore, non‐local allopatric fish were not better hosts than local fish in any of the FPM populations tested, neither in brown trout or salmon rivers and neither in abundance nor size of larvae. Therefore, the results supported the hypothesis that glochidia show local adaptation by being more successful when attached to local fish strains.

Thus, the local, sympatric fish strain should be preferred in FPM conservation programmes that involve captive breeding of juvenile mussels and introduction of host fish, but the regional assessment of local host dependency of FPM also would be important outside the current study area.

The results also indicate the importance of restoration of original salmonid populations in FPM rivers to enable the natural, effective reproduction cycle of FPM in their original, sympatric hosts, and thus to promote the recovery of endangered FPM populations.
Individual differences in social attachment: A multi‐disciplinary perspective
Authors: Gustison Morgan L. , Phelps Steven M.
Published: February 2022

Social behavior varies across both individuals and species. Research to explain this variation falls under the purview of multiple disciplines, each with its own theoretical and empirical traditions. Integration of these disciplinary traditions is key to developing a holistic perspective. Here, we review research on the biology of social attachment, a phenomena in which individuals develop strong affective connections to one another. We provide a historical overview of research on social attachment from psychological, ethological and neurobiological perspectives. As a case study, we describe work on pair‐bonding in prairie voles, a socially monogamous rodent. This specific topic takes advantage of many biological perspectives and techniques to explain social bonds. Lastly, we conclude with an overview of multi‐dimensional conceptual frameworks that can be used to explain social phenomena, and we propose a new framework for research on individual variation in attachment behavior. These conceptual frameworks originate from philosophy, physics, ethology, cognitive science and neuroscience. The application and synthesis of such frameworks offers a rich opportunity to advance understanding of social behavior and its mechanisms.
Orchestrated expression of vasculogenic mimicry and laminin‐5γ2 is an independent prognostic marker in oral squamous cell carcinoma
Authors: Saha Depanwita , Mitra Debarpan , Alam Neyaz , Sen Sagar , Mitra Mustafi Saunak , Mandal Syamsundar , Majumder Biswanath , Murmu Nabendu
Published: February 2022

Vasculogenic mimicry (VM), an endothelial cell–independent alternative mechanism of blood supply to the malignant tumour, has long been considered as an adverse prognostic factor in many cancers. The correlation of VM with laminin‐5γ2 and the assessment of their harmonized expression as an independent risk factor have not been elucidated yet in oral squamous cell carcinoma (OSCC). CD31/PAS staining stratified 116 clinically diagnosed OSCC specimens into VM+ and VM− cohorts. The expression pattern of laminin‐5γ2 and its upstream modulator MMP2 was evaluated by immunohistochemistry and Western blot. The Kaplan–Meier and Cox regression analyses were performed to assess the survival and prognostic implications. The presence of VM demonstrated a significant correlation with the expression of laminin‐5γ2 (p < .001) and MMP2 (p < .001). This pattern was mirrored by the significant upregulation of laminin‐5γ2 and MMP2 in VM+ cohorts compared with the VM− ones. Furthermore, co‐expression of VM and laminin‐5γ2 was significantly associated with tumour grade (p = .010), primary tumour size (p < .001), lymph node metastasis (p = .001) and TNM stages (p < .001) but not with patients' age, gender, tobacco and alcohol consumption habit. Vasculogenic mimicry and laminin‐5γ2 double‐positive cohort displayed a significantly poorer disease‐free survival (DFS) and overall survival (OS). Vasculogenic mimicry, laminin‐5γ2 and their subsequent dual expression underlie a significant prognostic value for DFS [hazard ratio (HR) = 9.896, p = .028] and OS [HR = 21.401, p = .033] in OSCC patients. Together, our findings imply that VM along with laminin‐5γ2 is strongly linked to the malignant progression in OSCC and VM and laminin‐5γ2 coordination emerges as a critical prognostic biomarker for OSCC.
Appearance‐related possessions and the transition to retired life
Authors: Ceballos Lina M. , Hodges Nancy
Published: February 2022

As life expectancies are rising worldwide, this qualitative study explores the meaning of appearance‐related possessions and their roles in the critical life transition to retirement among older males. Using an ethnographic approach, data were collected via in‐depth interviews and observation. Viewed through the conceptual lens of Turner's rites of passage, findings indicate retirement is experienced by older male consumers (+55 years old) as a ritual process with three phases (separation, transition, and incorporation) and two “areas” (pre‐ and post‐retirement). Interpreted through Symbolic Interaction theory, the multi‐layered meanings of favorite appearance‐related possessions as well as the way participants interacted with them changed over time depending on the rite of passage phase, the co‐existence of identities (working self vs. retired self), and the contradictions experienced during the process of reconstructing the self. Attachment, as well as detachment, were crucial to the way appearance‐related possessions supported and sometimes hindered the transition experience. Results show that it is in the having, as well as in the not having, that participants defined their identities during this process. Limited qualitative studies exist that explore male consumers, the process of retirement, and how possessions are used to navigate this major transition in life. Understanding retirement as a social process offers opportunities for theoretical and managerial contributions.
Predictors of contracting COVID‐19 in nursing homes: Implications for clinical practice
Authors: Aghili Mohammad Sadegh , Darvishpoor Kakhki Ali , Gachkar Latif , Davidson Patricia M.
Published: February 2022

Aims

The aim of the study was to identify the predictors of contracting COVID‐19 among older people in nursing homes in Iran.

Design

A case–control study.

Methods

Four‐hundred‐nine nursing home residents aged 60 years and above, with a 1:2 ratio of those infected with SARS‐CoV‐2 to those not infected, from six nursing homes in Tehran between 25 March and 12 July 2021 were recruited. Participants completed a questionnaire comprising demographic and underlying disease questions, practice about prevention principles of SARS‐CoV‐2 infection, probably predisposing factors of the infection, and environmental and staff characteristic of nursing homes. Logistic regression was used to determine risk factors associated with contracting COVID‐19.

Results

The mean age was 77.37 (±9.20) years; 54% were female. A logistic regression model showed that the most important predictors of becoming infected by SARS‐CoV‐2 included not using mask outside the room (odds ratio [OR]: 3.37, 95% CI: 1.74–6.53), longer staff shifts (OR: 3.02, 95% CI: 1.68–5.43), using cloth mask or not wearing a mask (OR: 2.47, 95% CI: 1.13–5.42) and not having glass barrier in visitors space (OR: 1.95, 95% CI: 1.11–3.50).

Conclusion

The results indicate that an increase in older people becoming infected by SARS‐CoV‐2 in nursing homes is probably because of not wearing a mask in common places, use of a cloth mask, longer staff shift durations and not having a glass shield when interacting with visitors from outside of nursing homes.

Impact

The predictors identified in this study can assist in reducing SARS‐CoV‐2 infections in older people institutionalized in nursing homes. These data items can also inform the development of interventions to improve principles of infection prevention and control.
Internalized skin bias: validation study to explore the impact of the internalization of social stigma on those with hidradenitis suppurativa
Authors: Butt M. , Chinchilli V.M. , Leslie D.L. , Khesroh E. , Helm M.F. , Flamm A. , Kirby J.S. , Rigby A.
Published: February 2022

Background

Hidradenitis suppurativa (HS) is a chronic auto‐inflammatory disease that is highly associated with adverse psychopathology and impaired body image. Previous studies show that patients with HS are also impacted by social stigma associated with their skin disease. Over time, these experiences can influence the way in which patients feel about themselves, leading to internalized skin bias (ISB).

Objectives

To evaluate the validity and reliability of the Internalized Skin Bias Questionnaire (ISBQ) in an HS population and to determine the association of this instrument with markers of HS severity.

Methods

A cross‐sectional survey with 72‐h retest was sent to adult patients with HS from March to November 2021. Reliability for the ISBQ was evaluated using Cronbach’s alpha and the Concordance Correlation Coefficient (CCC). Construct validity was evaluated using Pearson Correlation Coefficients with similar measures.

Results

Internal consistency for the ISBQ instrument was 0.89 with a CCC of 0.88. The ISBQ had moderate correlation (r = 0.63) with the experienced skin stigma questionnaire as well as the BDI‐II (r = 0.66) and the psychosocial subscale of the HiSQOL (r = 0.65). ISBQ scores differed significantly across different stages of disease severity (P = 0.04). There was no significant difference between those with different durations of disease (P = 0.47).

Conclusions

This study shows that the ISBQ is a valid and reliable instrument that can be used to assess the psychosocial construct of ISB especially in a population of HS patients. Further, ISB places a prevalent negative impact on the psychopathology of patients with HS.
Characterization of a novel picornavirus isolated from moribund gilthead seabream (Sparus aurata) larvae
Authors: Louboutin Lénaïg , Dheilly Nolwenn M , Cabon Joëlle , Picon Camacho Sara , Leroux Aurélie , Lucas Pierrick , Le Breton Alain , Blanchard Yannick , Morin Thierry
Published: February 2022

Gilthead seabream represents a species of importance in Mediterranean aquaculture. The larval stage is particularly sensitive and frequently impacted in suboptimal environmental or sanitary conditions. In the present study, investigations were carried out in a seabream hatchery following an unusual mortality reaching 70% among 50‐day post‐hatching. Anorexia, loss of appetite and abnormal swimming behaviour were observed in absence of parasites or pathogenic bacteria. Proliferation of rod‐shaped bacteria in the gut lumen was associated with focal degeneration in the intestinal mucosa. Cytopathic effects on an EK‐1 cell line after 21 days of culture at 14°C and 20°C in contact with homogenized affected larvae revealed the presence of a viral agent. Molecular characterization by high‐throughput sequencing showed a typical picornavirus genome organization with a polyprotein precursor of 2276 amino acids sharing 46.3% identity with that of the Eel Picornavirus‐1. A specific real‐time PCR confirmed the presence of the viral genome in affected larval homogenate and corresponding cell culture supernatant. We propose the name Potamipivirus daurada for this novel species within the genus Potamipivirus. The etiological role of this virus remains uncertain at this time, and future studies will be necessary to investigate its prevalence in natural and aquaculture‐reared populations as well as its ability to cause diseases in gilthead seabream.
Hospitalizations for chronic conditions following hurricanes among older adults: A self‐controlled case series analysis
Authors: Bell Sue Anne , Donnelly John P. , Li Wang , Davis Matthew A.
Published: February 2022

Background/Purpose

Extreme events such as hurricanes adversely impact healthcare systems and the communities they serve. The degree to which hurricanes affect healthcare use among high need groups such as older adults with chronic conditions has not been well examined, nor has the impact of hurricane severity on health outcomes. We characterized hospitalizations among older adults by chronic condition after eight large‐scale hurricanes in the United States.

Methods

Using a combination of administrative healthcare data and the Federal Emergency Management Agency's Disaster Declaration database we conducted a self‐controlled case series analysis. We identified Medicare beneficiaries who were exposed to one of eight hurricanes and compared hospitalizations in the 30‐days after a hurricane to hospitalizations in the rest of the calendar year of the hurricane. We examined hospitalizations (1) in total, (2) separately for diabetes, congestive heart failure (CHF) and chronic obstructive pulmonary disease (COPD) admissions, and (3) by hurricane damage category.

Results

Among all older adults exposed, hospitalizations in the 30‐day period after each disaster increased for all three chronic conditions; diabetes (incidence rate ratio [IRR] = 1.06, 95% confidence interval [CI] 1.03, 1.10), COPD (IRR = 1.06, 95% CI 1.04, 1.08), and CHF (IRR = 1.19, 95% CI 1.17, 1.21. In the 30‐to‐60‐day period hospitalizations also increased for each chronic condition; diabetes (IRR = 1.06, 95% CI 1.03, 1.10), COPD (IRR = 1.12, 95% CI 1.10, 1.15), and CHF (IRR = 1.32, 95% CI 1.30, 1.34). Substantial differences in hospitalizations were observed according to individual hurricane and by the chronic disease examined.

Conclusion

Exposure to hurricanes is associated with an increase in hospitalizations for chronic conditions across all hurricane damage categories. As disasters are expected to increase in strength and frequency, our results underscore the need for response strategies and health policy planning for healthcare systems designed to address the health needs of older Americans with chronic conditions.
Impact of a new young adult inflammatory bowel disease transition clinic on patient satisfaction and clinical outcomes
Authors: Mollah Taha , Lee Dongju , Giles Edward
Published: February 2022

Aim

The transition from paediatric to adult care for patients with inflammatory bowel disease (IBD) is associated with an increased risk of treatment non‐adherence, hospitalizations and emergency department (ED) use. We established a new young adult IBD clinic (YAC) in Melbourne to capture this at‐risk population. We aimed to assess patient satisfaction as well as clinical outcomes.

Methods

All patients who attended the YAC between its inception in November 2016 and November 2018 were recruited to our YAC group, 61 patients in total. A control group was selected from the pre‐existing adult clinic (AC) at our service, 34 patients in total. IBD‐related ED (IBD‐ED) visits were collected for all patients. We compared IBD‐ED visits in the 2 years before and after attending the clinic for the first time. Patient satisfaction was assessed using the IBD‐Patient Satisfaction Questionnaire.

Results

There was an overall decrease in IBD‐ED visits between the pre‐clinic and post‐clinic periods in both the YAC (42.9% reduction) and AC (69.2% reduction) (P < 0.001). Patient satisfaction was high amongst both services with YAC patients indicating higher satisfaction with communication (P = 0.015).

Conclusion

There was a reduction in IBD‐ED visits in both the YAC and the AC, high patient satisfaction, and statistically higher satisfaction with communication in the YAC. We speculate the importance of a YAC is to capture those patients in the peri‐transitional period at risk of being lost to follow‐up or not previously referred for specialist care.
The use of dental radiographs for age estimation of unaccompanied migrant minors: Scientific and ethical concerns
Authors: Laniado Nadia , Wright M. Lindsay , Seymour Brittany
Published: February 2022

Unaccompanied migrant minors are increasingly seeking asylum status in the United States (U.S.) where guidelines for age assessment call for the use of multiple forms of evidence. A commonly used approach in the U.S. is dental radiographs to assess the root development of third molars. Not only has research shown this methodology to be unreliable and imprecise, but the evidence has shown significant variability in dental development by chronologic age, race/ethnicity, sex, socioeconomic status, systemic disease, nutritional health, and other environmental factors. Misclassification of minors as adults based upon the imprecise tool of dental age assessment can have serious and harmful consequences. In the U.S., this misclassification has resulted in the housing of minors with adults in Immigrant and Custom Enforcement (ICE) operated jails. In addition, there are significant ethical concerns with regard to the use of radiographs for purposes that are neither diagnostic nor therapeutic and the lack of informed consent. In this commentary we review the (1) inadequacy of dental radiographs as a means of chronologic age assessment for minors, and (2) the ethical implications of implementing this flawed and inappropriate assessment on a highly vulnerable population.
The effect of temporal variation of prelaunch expectations on stock market response in the motion picture industry
Authors: Kim Junhee , Song Reo , Kang Wooseong
Published: February 2022

This research provides novel insights into the marketing–finance literature by shedding new light on the association between the temporal variation of prelaunch expectations of a new product's market performance and postlaunch firm value. We establish the nature of this relationship from theoretical underpinnings of psychological tendencies such as reference dependence and recency effect. Drawing from the emerging literature on crowdsourced earnings forecasts, we use crowdsourced expectations provided by a prediction market as a proxy for the market's expectations. The results show that two varying patterns of expectations play a critical role in driving postlaunch firm value. Specifically, the last‐moment variation of prelaunch expectations (i.e., last‐moment increase or decrease) is negatively related to firms' postlaunch stock price response, while the overall expectation level (i.e., high vs. low mean level) moderates the negative relationship between the last‐moment variation of expectations and firm value.
Effect of sevoflurane preconditioning on sleep reintegration after alteration by lipopolysaccharide
Authors: Nemoto Tsuyoshi , Irukayama‐Tomobe Yoko , Hirose Yuki , Tanaka Hiromu , Takahashi Genki , Takahashi Satoshi , Yanagisawa Masashi , Kanbayashi Takashi
Published: February 2022

Despite extensive evidence on the organ protective effects of sevoflurane, its effect on disturbed sleep remains unclear. We hypothesised that sevoflurane preconditioning positively impacts disturbed sleep caused by systemic inflammation. A prospective, randomised laboratory investigation was conducted in C57BL/6J mice. A mouse model of lipopolysaccharide (LPS)‐induced systemic inflammation was employed to investigate the effects of sevoflurane on sleep recovery. Symptom recovery was evaluated through electroencephalography/electromyography (EEG/EMG) and histological studies. The mice were exposed to 2% sevoflurane before and after peritoneal injection of LPS. The EEG and EMG were recorded for 24 h after the procedure. Brain tissue was harvested after the sevoflurane/LPS procedure and was immunostained using individual antibodies against choline acetyltransferase (ChAT) and Fos. The ChAT‐positive and ChAT/Fos double‐positive cells were analysed quantitatively in the pedunculopontine tegmental nucleus and laterodorsal tegmental nucleus (PPTg/LDTg). Compared with control mice, mice preconditioned with sevoflurane but not post‐conditioned showed a significant increase in rapid eye movement (REM) sleep during EEG recording following the LPS challenge. They also demonstrated a shorter REM latency, indicating an early recovery from LPS‐altered sleep. The bouts of REM episodes were retained with sevoflurane preconditioning. More ChAT/Fos double‐positive cells were observed in the PPTg/LDTg in the sevoflurane preconditioning plus LPS group than in the LPS‐only group. Sevoflurane preconditioning promotes recovery from altered sleep induced by systemic inflammation. Activation of PPTg/LDTg is considered a mechanism underlying sleep reintegration. The recovery phenomenon shows potential for clinical application in cases of sleep disturbances induced by systemic inflammation.
Incidence, risk factors, and outcomes for early postoperative seizures in dogs with rostrotentorial brain tumors after intracranial surgery
Authors: Parker Rell L. , Du John , Shinn Richard L. , Drury Adam G. , Hsu Fang‐Chi , Roberston John L. , Cecere Thomas E. , Arendse Avril U. , Rossmeisl John H.
Published: February 2022

Background

Seizures in the early postoperative period after intracranial surgery may affect outcome in dogs.

Objectives

To determine the incidence of early postoperative seizures (EPS) in dogs with brain tumors, identify specific risk factors for EPS, and determine if EPS affects outcome.

Animals

Eighty‐eight dogs that underwent 125 intracranial surgeries for diagnosis and treatment of rostrotentorial brain tumors.

Methods

Retrospective cohort study. All patients with a diagnosis of rostrotentorial brain tumor from 2006 to 2020 were included. Early postoperative seizures were diagnosed by observation of seizure activity within 14 days of neurosurgery. Previously diagnosed structural epilepsy, perioperative anticonvulsant drug (ACD) use, magnetic resonance imaging (MRI), and tumor characteristics were evaluated. Outcome measures included neurologic and nonneurologic complications, duration of hospitalization, and survival to discharge.

Results

Dogs with rostrotentorial brain tumors had EPS after 16/125 (12.8%) neurosurgical procedures (95% confidence interval [CI], 7%‐19%). Presence of previous structural epilepsy was not associated with EPS risk (P = 1). Perioperative ACD use also was not associated with EPS (P = .06). Dogs with EPS had longer hospitalization (P < .001), were more likely to have neurologic complications postsurgery (P = .01), and were less likely to survive to discharge (P = .01).

Conclusions and Clinical Importance

It is difficult to predict which dogs are at risk of EPS because the presence of previous structural epilepsy and the use of perioperative ACDs was not associated with EPS. However, seizures in the early postoperative period are clinically important because affected dogs had prolonged hospitalization, more neurologic complications, and decreased short‐term survival.
Understory plant species and community changes following a mountain pine beetle outbreak in Rocky Mountain National Park, USA
Authors: Pappas Gregory S. , Tinker Daniel B. , Rocca Monique E.
Published: February 2022

Aims

The response of understory plants is an important, yet understudied element of forest dynamics associated with mountain pine beetle (MPB) disturbance. Here, we provide a detailed assessment of both the changes in understory species and communities over a 5‐year period following severe MPB‐induced lodgepole pine mortality. Specifically, we examine species turnover, rarity and mobility over time, and evaluate shifts in community composition, including the potential for post‐outbreak community homogenization or differentiation.

Location

Western Rocky Mountain National Park in the southern Rocky Mountains, Colorado.

Methods

We collected species occurrence data across lodgepole pine‐dominated forest understories using repeated sampling of the same study sites (during the peak of MPB activity and 5 years after).

Results

More species appeared than disappeared 5 years after the peak of the outbreak. New species were comprised of both early‐ and late‐successional species, suggesting the presence of rather high microhabitat heterogeneity. Although most species remained relatively rare, the number of exceedingly rare species decreased, and the number of highly common species increased. Several species were able to take advantage of the new stand conditions and expand throughout the study area. Some species appeared to spread locally over short distances mainly via vegetative reproduction, others expanded primarily upwards in elevation, probably through long‐distance dispersal and some spread over both short and long distances. Non‐native species doubled in occurrence and tended to spread upslope, towards the interior of the park, yet remained a small component of the understory overall. Shifts in community composition were minimal, but a slight convergence of plant community groups suggests a trend towards community homogenization.

Conclusions

Our results demonstrate that even relatively sparse and depauperate lodgepole pine forest understories may be altered in diverse ways following MPB‐induced overstory mortality, depending on the unique ability of species to respond to changes in site conditions and resource availability.
Tomato CRABS CLAW paralogues interact with chromatin remodelling factors to mediate carpel development and floral determinacy
Authors: Castañeda Laura , Giménez Estela , Pineda Benito , García‐Sogo Begoña , Ortiz‐Atienza Ana , Micol‐Ponce Rosa , Angosto Trinidad , Capel Juan , Moreno Vicente , Yuste‐Lisbona Fernando J. , Lozano Rafael
Published: February 2022

CRABS CLAW (CRC) orthologues play a crucial role in floral meristem (FM) determinacy and gynoecium formation across angiosperms, the key developmental processes for ensuring successful plant reproduction and crop production. However, the mechanisms behind CRC mediated FM termination are far from fully understood.

Here, we addressed the functional characterization of tomato (Solanum lycopersicum) paralogous CRC genes. Using mapping‐by‐sequencing, RNA interference and CRISPR/Cas9 techniques, expression analyses, protein–protein interaction assays and Arabidopsis complementation experiments, we examined their potential roles in FM determinacy and carpel formation.

We revealed that the incomplete penetrance and variable expressivity of the indeterminate carpel‐inside‐carpel phenotype observed in fruit iterative growth (fig) mutant plants are due to the lack of function of the S. lycopersicum CRC homologue SlCRCa. Furthermore, a detailed functional analysis of tomato CRC paralogues, SlCRCa and SlCRCb, allowed us to propose that they operate as positive regulators of FM determinacy by acting in a compensatory and partially redundant manner to safeguard the proper formation of flowers and fruits.

Our results uncover for the first time the physical interaction of putative CRC orthologues with members of the chromatin remodelling complex that epigenetically represses WUSCHEL expression through histone deacetylation to ensure the proper termination of floral stem cell activity.
Plant volatiles as regulators of hormone homeostasis
Authors: Dani Kaidala Ganesha Srikanta , Loreto Francesco
Published: February 2022

Some canonical plant hormones such as auxins and gibberellins have precursors that are biogenic volatiles (indole, indole acetonitrile, phenylacetaldoxime and ent‐kaurene). Cytokinins, abscisic acid and strigolactones are hormones comprising chemical moieties that have distinct volatile analogues, and are synthesised alongside constitutively emitted volatiles (isoprene, sesquiterpenes, lactones, benzenoids and apocarotenoid volatiles). Nonvolatile hormone analogues and biogenic volatile organic compounds (BVOCs) evolved in tandem as growth and behavioural regulators in unicellular organisms. In plants, however, nonvolatile hormones evolved as regulators of growth, development and differentiation, while endogenous BVOCs (often synthesised lifelong) became subtle regulators of hormone synthesis, availability, activity and turnover, all supported by functionally redundant components of hormone metabolism. Reciprocal changes in the abundance and activity of hormones, nitric oxide, and constitutive plant volatiles constantly bridge retrograde and anterograde signalling to maintain hormone equilibria even in unstressed plants. This is distinct from transient interference in hormone signalling by stress‐induced and exogenously received volatiles.
CHEVAUX DE FRISEOF THE IRISH AND BRITISH ISLES
Authors: O’Driscoll James
Published: February 2022

Chevaux de friseis a term describing a series of deliberately introduced stones or wooden stakes positioned outside an ancient fortification. Only a handful of such sites in Ireland and Britain have been recorded, with a much larger concentration found in the Iberian Peninsula. Traditionally,chevaux de friseis assumed to have originated in Central or Eastern Europe around 800–600 BC before spreading westwards, appearing as a defensive reaction to the use of horses in warfare. However, recent work on Iberian examples have begun to identify Bronze Age precursors as well as challenging the traditional defensive interpretation. This paper, for the first time since Harbison’s seminal work on the subject in 1971, brings together the most recent evidence from Ireland and Britain, identifying a similar Bronze Age horizon and highlighting the potential defensive, and non‐defensive, functions ofchevaux de frise.
Clinical effectiveness of baloxavir marboxil against influenza in three seasons
Authors: Kakuya Fujio , Okubo Hitoshi , Fujiyasu Hiroaki , Kurisawa Mio June , Kinebuchi Takahiro
Published: February 2022

Background

Previous reports have not clarified the difference in clinical efficacy between baloxavir and oseltamivir against influenza.

Methods

A prospective observational study was performed during 2017–2018, 2018–2019, and 2019–2020 influenza seasons. The primary endpoint of this study was to compare the duration of fever between patients who received baloxavir and those who received oseltamivir.

Results

A total of 235 influenza‐infected patients (3–18 years of age), including 91 who received oseltamivir and 144 who received baloxavir, were enrolled. The proportions of influenza A(H3N2) virus, influenza A(H1N1)pdm09 virus, and influenza B virus‐infected patients were 31.5%, 42.6%, and 26.0%, respectively. Patients who received oseltamivir were significantly younger than those who received baloxavir. Univariate analyses showed that the duration of fever was shorter with baloxavir than with oseltamivir against influenza virus overall, influenza A virus, influenza B virus, and influenza A(H1N1)pdm09 virus, but not for influenza A(H3N2) virus. In multivariate analyses, hazard ratios for influenza virus overall (0.53 [95% CI, 0.38–0.73]), influenza B virus (0.16 [95% CI, 0.07–0.41]), and influenza A(H1N1)pdm09 virus (0.55 [95% CI, 0.32–0.93]) were significantly lower in the patients who received baloxavir than those who received oseltamivir. However, the differences between influenza A virus and influenza A(H3N2) virus were not significant between the two groups.

Conclusion

For influenza virus overall, influenza B virus, and influenza A(H1N1)pdm09 virus, baloxavir treatment resulted in shorter duration of fever than oseltamivir treatment, but not for influenza A virus and influenza A(H3N2) virus.
Boundary Conditions Matter—Impact of Test Setup on Inferred Construct Mechanics in Plated Distal Femur Osteotomies
Authors: Inacio Jordan V. , Schwarzenberg Peter , Yoon Richard S. , Kantzos Andrew , Malige Ajith , Nwachuku Chinenye O. , Dailey Hannah L.
Published: February 2022

The mechanics of distal femur fracture fixation has been widely studied in bench tests that employ a variety of approaches for holding and constraining femurs to apply loads. No standard test methods have been adopted for these tests and the impact of test setup on inferred construct mechanics has not been reported. Accordingly, the purpose of this study was to use finite element models to compare the mechanical performance of a supracondylar osteotomy with lateral plating under conditions that replicate several common bench test methods. A literature review was used to define a parameterized virtual model of a plated distal femur osteotomy in axial compression loading with four boundary condition sets ranging from minimally to highly constrained. Axial stiffness, fracture gap closure, and transverse motion at the fracture line were recorded for a range of applied loads and bridge spans. The results showed that construct mechanical performance was highly sensitive to boundary conditions imposed by the mechanical test fixtures. Increasing the degrees of constraint, for example, by potting and rigidly clamping one or more ends of the specimen, caused up to a 25× increase in axial stiffness of the construct. Transverse motion and gap closure at the fracture line, which is an important driver of interfragmentary strain, was also largely influenced by the constraint test setup. These results suggest that caution should be used when comparing reported results between bench tests that use different fixtures and that standardization of testing methods is needed in this field.
Analyses of internal structures and defects in materials using physics-informed neural networks
Authors: Zhang Enrui , Dao Ming , Karniadakis George Em , Suresh Subra
Published: February 2022

Characterizing internal structures and defects in materials is a challenging task, often requiring solutions to inverse problems with unknown topology, geometry, material properties, and nonlinear deformation. Here, we present a general framework based on physics-informed neural networks for identifying unknown geometric and material parameters. By using a mesh-free method, we parameterize the geometry of the material using a differentiable and trainable method that can identify multiple structural features. We validate this approach for materials with internal voids/inclusions using constitutive models that encompass the spectrum of linear elasticity, hyperelasticity, and plasticity. We predict the size, shape, and location of the internal void/inclusion as well as the elastic modulus of the inclusion. Our general framework can be applied to other inverse problems in different applications that involve unknown material properties and highly deformable geometries, targeting material characterization, quality assurance, and structural design.
2.4-Å structure of the double-ring
Gemmatimonas phototrophica
photosystem
Authors: Qian Pu , Gardiner Alastair T. , Šímová Ivana , Naydenova Katerina , Croll Tristan I. , Jackson Philip J. , Nupur  , Kloz Miroslav , Čubáková Petra , Kuzma Marek , Zeng Yonghui , Castro-Hartmann Pablo , van Knippenberg Bart , Goldie Kenneth N. , Kaftan David , Hrouzek Pavel , Hájek Jan , Agirre Jon , Siebert C. Alistair , Bína David , Sader Kasim , Stahlberg Henning , Sobotka Roman , Russo Christopher J. , Polívka Tomáš , Hunter C. Neil , Koblížek Michal
Published: February 2022

Phototrophic Gemmatimonadetes evolved the ability to use solar energy following horizontal transfer of photosynthesis-related genes from an ancient phototrophic proteobacterium. The electron cryo-microscopy structure of the
Gemmatimonas phototrophica
photosystem at 2.4 Å reveals a unique, double-ring complex. Two unique membrane-extrinsic polypeptides, RC-S and RC-U, hold the central type 2 reaction center (RC) within an inner 16-subunit light-harvesting 1 (LH1) ring, which is encircled by an outer 24-subunit antenna ring (LHh) that adds light-gathering capacity. Femtosecond kinetics reveal the flow of energy within the RC-dLH complex, from the outer LHh ring to LH1 and then to the RC. This structural and functional study shows that
G. phototrophica
has independently evolved its own compact, robust, and highly effective architecture for harvesting and trapping solar energy.
Personalized chordoma organoids for drug discovery studies
Authors: Al Shihabi Ahmad , Davarifar Ardalan , Nguyen Huyen Thi Lam , Tavanaie Nasrin , Nelson Scott D. , Yanagawa Jane , Federman Noah , Bernthal Nicholas , Hornicek Francis , Soragni Alice
Published: February 2022

Chordomas are rare tumors of notochordal origin, most commonly arising in the sacrum or skull base. Chordomas are considered insensitive to conventional chemotherapy, and their rarity complicates running timely and adequately powered trials to identify effective treatments. Therefore, there is a need for discovery of novel therapeutic approaches. Patient-derived organoids can accelerate drug discovery and development studies and predict patient responses to therapy. In this proof-of-concept study, we successfully established organoids from seven chordoma tumor samples obtained from five patients presenting with tumors in different sites and stages of disease. The organoids recapitulated features of the original parent tumors and inter- as well as intrapatient heterogeneity. High-throughput screenings performed on the organoids highlighted targeted agents such as PI3K/mTOR, EGFR, and JAK2/STAT3 inhibitors among the most effective molecules. Pathway analysis underscored how the NF-κB and IGF-1R pathways are sensitive to perturbations and potential targets to pursue for combination therapy of chordoma.
Integrated -omics approach reveals persistent DNA damage rewires lipid metabolism and histone hyperacetylation via MYS-1/Tip60
Authors: Hamsanathan Shruthi , Anthonymuthu Tamil , Han Suhao , Shinglot Himaly , Siefken Ella , Sims Austin , Sen Payel , Pepper Hannah L. , Snyder Nathaniel W. , Bayir Hulya , Kagan Valerian , Gurkar Aditi U.
Published: February 2022

Although DNA damage is intricately linked to metabolism, the metabolic alterations that occur in response to DNA damage are not well understood. We use a DNA repair–deficient model of ERCC1-XPF in
Caenorhabditis elegans
to gain insights on how genotoxic stress drives aging. Using multi-omic approach, we discover that nuclear DNA damage promotes mitochondrial β-oxidation and drives a global loss of fat depots. This metabolic shift to β-oxidation generates acetyl–coenzyme A to promote histone hyperacetylation and an associated change in expression of immune-effector and cytochrome genes. We identify the histone acetyltransferase MYS-1, as a critical regulator of this metabolic-epigenetic axis. We show that in response to DNA damage, polyunsaturated fatty acids, especially arachidonic acid (AA) and AA-related lipid mediators, are elevated and this is dependent on
mys-1
. Together, these findings reveal that DNA damage alters the metabolic-epigenetic axis to drive an immune-like response that can promote age-associated decline.
Efficient healing of large osseous segmental defects using optimized chemically modified messenger RNA encoding BMP-2
Authors: De La Vega Rodolfo E. , van Griensven Martijn , Zhang Wen , Coenen Michael J. , Nagelli Christopher V. , Panos Joseph A. , Peniche Silva Carlos J. , Geiger Johannes , Plank Christian , Evans Christopher H. , Balmayor Elizabeth R.
Published: February 2022

Large segmental osseous defects heal poorly. Recombinant, human bone morphogenetic protein-2 (rhBMP-2) is used clinically to promote bone healing, but it is applied at very high doses that cause adverse side effects and raise costs while providing only incremental benefit. We describe a previously unexplored, alternative approach to bone regeneration using chemically modified messenger RNA (cmRNA). An optimized cmRNA encoding BMP-2 was delivered to critical-sized femoral osteotomies in rats. The cmRNA remained orthotopically localized and generated BMP locally for several days. Defects healed at doses ≥25 μg of BMP-2 cmRNA. By 4 weeks, all animals treated with 50 μg of BMP-2 cmRNA had bridged bone defects without forming the massive callus seen with rhBMP-2. Moreover, such defects recovered normal mechanical strength quicker and initiated bone remodeling faster. cmRNA regenerated bone via endochondral ossification, whereas rhBMP-2 drove intramembranous osteogenesis; cmRNA provides an innovative, safe, and highly translatable technology for bone healing.
A SARS-CoV-2 ferritin nanoparticle vaccine elicits protective immune responses in nonhuman primates
Authors: Joyce M. Gordon , King Hannah A. D. , Elakhal-Naouar Ines , Ahmed Aslaa , Peachman Kristina K. , Macedo Cincotta Camila , Subra Caroline , Chen Rita E. , Thomas Paul V. , Chen Wei-Hung , Sankhala Rajeshwer S. , Hajduczki Agnes , Martinez Elizabeth J. , Peterson Caroline E. , Chang William C. , Choe Misook , Smith Clayton , Lee Parker J. , Headley Jarrett A. , Taddese Mekdi G. , Elyard Hanne A. , Cook Anthony , Anderson Alexander , McGuckin Wuertz Kathryn , Dong Ming , Swafford Isabella , Case James Brett , Currier Jeffrey R. , Lal Kerri G. , Molnar Sebastian , Nair Manoj S. , Dussupt Vincent , Daye Sharon P. , Zeng Xiankun , Barkei Erica K. , Staples Hilary M. , Alfson Kendra , Carrion Ricardo , Krebs Shelly J. , Paquin-Proulx Dominic , Karasavva Nicos , Polonis Victoria R. , Jagodzinski Linda L. , Amare Mihret F. , Vasan Sandhya , Scott Paul T. , Huang Yaoxing , Ho David D. , de Val Natalia , Diamond Michael S. , Lewis Mark G. , Rao Mangala , Matyas Gary R. , Gromowski Gregory D. , Peel Sheila A. , Michael Nelson L. , Bolton Diane L. , Modjarrad Kayvon
Published: February 2022

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants stresses the continued need for next-generation vaccines that confer broad protection against coronavirus disease 2019. We developed and evaluated an adjuvanted SARS-CoV-2 spike ferritin nanoparticle (SpFN) vaccine in nonhuman primates. High-dose (50-μg) SpFN vaccine, given twice 28 days apart, induced a T helper cell 1 (T
H
1)–biased CD4 T
H
response and elicited neutralizing antibodies against SARS-CoV-2 wild type and variants of concern, as well as against SARS-CoV-1. These potent humoral and cell-mediated immune responses translated into rapid elimination of replicating virus in the upper and lower airways and lung parenchyma of nonhuman primates after high-dose SARS-CoV-2 respiratory challenge. The immune response elicited by SpFN vaccination and resulting efficacy in nonhuman primates support the utility of SpFN as a vaccine candidate for SARS-causing betacoronaviruses.
Optimizing Nanopore Sequencing for Rapid Detection of Microbial Species and Antimicrobial Resistance in Patients at Risk of Surgical Site Infections
Authors: Whittle Emma , Yonkus Jennifer A. , Jeraldo Patricio , Alva-Ruiz Roberto , Nelson Heidi , Kendrick Michael L. , Grys Thomas E. , Patel Robin , Truty Mark J. , Chia Nicholas
Published: February 2022

Surgical site infections (SSI) are a significant burden to patients and health care systems. They increase mortality rates, length of hospital stays, and associated health care costs.