bluuebunny/crossref_metadata_2025 huggingface dataset:
Preoperative prophylactic active vitamin D to streamline total thyroidectomy
Authors: Annebäck Matilda , McHale Sjödin Edward , Hellman Per , Stålberg Peter , Norlén Olov
Published: May 2022

Background

Hypocalcaemia is a common complication after total thyroidectomy (TT). Treatment consists of calcium and active vitamin D supplementation. Low levels of vitamin D before surgery have been shown to be a risk factor for postoperative hypocalcaemia, yet studies examining routine preoperative vitamin D supplementation have shown conflicting results. This retrospective cohort study aims to investigate the potential benefit of preoperative active vitamin D supplementation on hypocalcaemia and its symptoms after TT.

Methods

This study included patients undergoing TT at Uppsala University Hospital from January 2013 to December 2020, resulting in a total of 401 patients after exclusion. Routine preoperative alfacalcidol treatment was initiated for all TT patients in January 2017 resulting in two groups for comparison: one group (pre-January 2017) that was prescribed preoperative alfacalcidol and one that was not. Propensity score matching was used to reduce bias. The primary outcome was early postoperative hypocalcaemia (serum calcium, S-Ca less than 2.10 mmol/l); secondary outcomes were symptoms of hypocalcaemia and length of stay.

Results

After propensity score matching, there were 108 patients in each group. There were 2 cases with postoperative day one S-Ca less than 2.10 in the treated group and 10 cases in the non-treated group (P < 0.001). No patients in the treated group had a S-Ca below 2.00 mmol/l. Preoperative alfacalcidol was associated with higher mean serum calcium level day one (2.33 versus 2.27, P = 0.022), and reduced duration of hospital stay (P < 0.001). There was also a trend toward fewer symptoms of hypocalcaemia (18.9 per cent versus 30.5 per cent, P = 0.099).

Conclusions

Prophylactic preoperative alfacalcidol was associated with reduced biochemical hypocalcaemia and duration of hospital stay following TT. Also, with this protocol, it is suggested that routine day 1 postoperative S-Ca measurement is not required.
Assessment of parental benzo[a]pyrene exposure-induced cross-generational neurotoxicity and changes in offspring sperm DNA methylome in medaka fish
Authors: Wan Teng , Au Doris Wai-Ting , Mo Jiezhang , Chen Lianguo , Cheung Kwok-Ming , Kong Richard Yuen-Chong , Seemann Frauke
Published: May 2022

Previous studies have revealed that DNA methylation changes could serve as potential genomic markers for environmental benzo[a]pyrene (BaP) exposure and intergenerational inheritance of various physiological impairments (e.g. obesity and reproductive pathologies). As a typical aromatic hydrocarbon pollutant, direct BaP exposure has been shown to induce neurotoxicity. To unravel the inheritance mechanisms of the BaP-induced bone phenotype in freshwater medaka, we conducted whole-genome bisulfite sequencing of F1 sperm and identified 776 differentially methylated genes (DMGs). Ingenuity pathway analysis revealed that DMGs were significantly enriched in pathways associated with neuronal development and function. Therefore, it was hypothesized that parental BaP exposure (1 μg/l, 21 days) causes offspring neurotoxicity. Furthermore, the possibility for sperm methylation as an indicator for a neurotoxic phenotype was investigated. The F0 adult brains and F1 larvae were analyzed for BaP-induced direct and inherited toxicity. Acetylcholinesterase activity was significantly reduced in the larvae, together with decreased swimming velocity. Molecular analysis revealed that the marker genes associated with neuron development and growth (alpha1-tubulin, mbp, syn2a, shh, and gap43) as well as brain development (dlx2, otx2, and krox-20) were universally downregulated in the F1 larvae (3 days post-hatching). While parental BaP exposure at an environmentally relevant concentration could induce neurotoxicity in the developing larvae, the brain function of the exposed F0 adults was unaffected. This indicates that developmental neurotoxicity in larvae may result from impaired neuronal development and differentiation, causing delayed brain growth. The present study demonstrates that the possible adverse health effects of BaP in the environment are more extensive than currently understood. Thus, the possibility of multigenerational BaP toxicity should be included in environmental risk assessments.
Trade globalization and social spending in Spain, 1850–2000
Authors: Espuelas Sergio
Published: May 2022

Between 1850 and 2000, Spanish trade openness experienced major changes. What was the impact on social spending? The econometric results suggest that globalization effect was conditional on fiscal capacity. When fiscal capacity was high (after the 1960s), trade openness had a positive effect on social spending. However, when fiscal capacity was low, trade openness effect was negative. The results are robust to alternative measures of fiscal capacity and consistent with a placebo test. Both the compensation effect and the race-to-the-bottom hypothesis find some empirical support: the final outcome depends on fiscal capacity.
Mobile Technology for Falls Prevention in Older Adults
Authors: Hsieh Katherine L , Chen Lingjun , Sosnoff Jacob J
Published: May 2022

Falls are the leading cause of accidental death in older adults that result from a complex interplay of risk factors. Recently, the need for person-centered approach utilizing personalization, prediction, prevention, and participation, known as the P4 model, in fall prevention has been highlighted. Features of mobile technology make it a suitable technological infrastructure to employ such an approach. This narrative review aims to review the evidence for using mobile technology for personalized fall risk assessment and prevention since 2017 in older adults. We aim to identify lessons learned and future directions for using mobile technology as a fall risk assessment and prevention tool. Articles were searched in PubMed and Web of Science with search terms related to older adults, mobile technology, and falls prevention. A total of 23 articles were included. Articles were identified as those examining aspects of the P4 model including prediction (measurement of fall risk), personalization (usability), prevention, and participation. Mobile technology appears to be comparable to gold-standard technology in measuring well-known fall risk factors including static and dynamic balance. Seven applications were developed to measure different fall risk factors and tested for personalization, and/or participation aspects, and 4 were integrated into a falls prevention program. Mobile health technology offers an innovative solution to provide tailored fall risk screening, prediction, and participation. Future studies should incorporate multiple, objective fall risk measures and implement them in community settings to determine if mobile technology can offer tailored and scalable interventions.
Functional Transcriptomic Analysis of Centenarians’ Offspring Reveals a Specific Genetic Footprint That May Explain That They Are Less Frail Than Age-Matched Noncentenarians’ Offspring
Authors: Inglés Marta , Belenguer-Varea Angel , Serna Eva , Mas-Bargues Cristina , Tarazona-Santabalbina Francisco J , Borrás Consuelo , Vina Jose
Published: May 2022

Centenarians exhibit extreme longevity and compression of morbidity and display a unique genetic signature. Centenarians’ offspring seem to inherit centenarians’ compression of morbidity, as measured by lower rates of age-related pathologies. We aimed to ascertain whether centenarians’ offspring are less frail and whether they are endowed with a “centenarian genetic footprint” in a case–control study, matched 1:1 for gender, age ±5 years, and place of birth and residence. Cases must have a living parent aged 97 years or older, aged 65–80 years, community dwelling, not suffering from a terminal illness, or less than 6 months of life expectancy. Controls had to meet the same criteria as cases except for the age of death of their parents (not older than 89 years). Centenarians were individuals 97 years or older. Frailty phenotype was determined by Fried’s criteria. We collected plasma and peripheral blood mononuclear cells from 63 centenarians, 88 centenarians’ offspring, and 88 noncentenarians’ offspring. miRNA expression and mRNA profiles were performed by the GeneChip miRNA 4.0 Array and GeneChip Clariom S Human Array, respectively. We found a lower incidence of frailty among centenarians’ offspring when compared with their contemporaries’ noncentenarians’ offspring (p < .01). Both miRNA and mRNA expression patterns in centenarians’ offspring were more like those of centenarians than those of noncentenarians’ offspring (p < .01). In conclusion, centenarians’ offspring are less frail than age-matched noncentenarians’ offspring, and this may be explained by their unique genetic endowment.
Relationships of Cerebral Perfusion With Gait Speed Across Systolic Blood Pressure Levels and Age: A Cohort Study
Authors: Windham B Gwen , Griswold Michael E , Ranadive Radhikesh , Sullivan Kevin J , Mosley Thomas H , Mielke Michelle M , Jack Clifford R , Knopman Dave , Petersen Ron , Vemuri Prashanthi
Published: May 2022

Background

This study aimed to examine if the association of cerebral perfusion with gait speed differs across systolic blood pressure (SBP) and age.

Methods

Cerebral perfusion was measured via arterial spin labeled (ASL)-MRI among community-dwelling adults aged 31–94 years in the population-based Mayo Clinic Study of Aging. Usual gait speed was assessed over 5.6 meters on an electronic mat. Sex- and body mass index (BMI)-adjusted linear regression models estimated cross-sectional gait speed associations with ASL and modifying effects of age and SBP using 3-way and 2-way interaction terms between continuous age, SBP, and ASL. Results report estimated differences in gait speed per standard deviation (SD) lower ASL for exemplar SBPs and ages.

Results

Among 479 participants (mean age 67.6 years; 44% women; mean gait speed 1.17 m/s), ASL relations to gait speed varied by age (ASL-x–age interaction: p = .001) and SBP (ASL-x–SBP interaction: p = .009). At an SBP of 120 mmHg, each SD lower ASL was associated with a 0.04 m/s (95% confidence interval [CI]: 0.01, 0.07) slower gait speed at 65 years, 0.07 m/s (0.04, 0.10) at 75 years, and 0.09 m/s (0.05, 0.13) at 85 years. At an SBP of 140 mmHg, ASL associations with gait speed were attenuated to 0.01 (−0.01, 0.04), 0.04 (0.02, 0.06), and 0.06 (0.04, 0.09) m/s slower gait speed at ages 65, 75, and 85, respectively.

Conclusion

Poorer cerebral perfusion is associated with clinically meaningful slower gait speeds, particularly with older age, while higher perfusion markedly attenuates age differences in gait speed.
Targeting the high affinity receptor, FcγRI, in autoimmune disease, neuropathy, and cancer
Authors: Holtrop Tosca , Budding Kevin , Brandsma Arianne M , Leusen Jeanette H W
Published: May 2022

The Fc gamma receptor I (FcγRI or CD64) is the only human Fc receptor with a high affinity for monomeric IgG. It plays a crucial role in immunity, as it mediates cellular effector functions of antibodies including phagocytosis, antigen presentation, and cytokine production. FcγRI is constitutively saturated with monomeric IgG and this feeds the dogma that it has no role in immune responses. However, recent findings have implicated a role for FcγRI in various autoimmune disorders, neuropathies, and antibody therapy in tumor models. By a process known as ‘inside-out’ signaling, stimulation of myeloid cells with cytokines such as tumor necrosis factor alpha (TNF-α) and interferon-gamma (IFN-γ) enhances FcγRI binding to immune complexes (ICs), including antibody-opsonized pathogens or tumor cells.

This review focuses on the current knowledge on interaction of FcγRI with IgG and ICs and the effect of inside-out signaling on FcγRI functioning. Additionally, this review will address potential clinical applications of targeting FcγRI, and the tools that can be used to overcome IC-mediated autoimmune diseases on the one hand, and to enhance antibody-based anti-cancer therapy on the other.
Using the biomarker cotinine and survey self-report to validate smoking data from United States Veterans Health Administration electronic health records
Authors: McGinnis Kathleen A , Skanderson Melissa , Justice Amy C , Tindle Hilary A , Akgün Kathleen M , Wrona Aleksandra , Freiberg Matthew S , Goetz Matthew Bidwell , Rodriguez-Barradas Maria C , Brown Sheldon T , Crothers Kristina A
Published: May 2022

Objective

Tobacco use/smoking for epidemiologic studies is often derived from electronic health record (EHR) data, which may be inaccurate. We previously compared smoking from the United States Veterans Health Administration (VHA) EHR clinical reminder data with survey data and found excellent agreement. However, the smoking clinical reminder items changed October 1, 2018. We sought to use the biomarker salivary cotinine (cotinine ≥30) to validate current smoking from multiple sources.

Materials and Methods

We included 323 Veterans Aging Cohort Study participants with cotinine, clinical reminder, and self-administered survey smoking data from October 1, 2018 to September 30, 2019. We included International Classification of Disease (ICD)-10 codes F17.21 and Z72.0. Operating characteristics and kappa statistics were calculated.

Results

Participants were mostly male (96%), African American (75%) and mean age was 63 years. Of those identified as currently smoking based on cotinine, 86%, 85%, and 51% were identified as currently smoking based on clinical reminder, survey, and ICD-10 codes, respectively. Of those identified as not currently smoking based on cotinine, 95%, 97%, and 97% were identified as not currently smoking based on clinical reminder, survey, and ICD-10 codes. Agreement with cotinine was substantial for clinical reminder (kappa = .81) and survey (kappa = .83), but only moderate for ICD-10 (kappa = .50).

Discussion

To determine current smoking, clinical reminder, and survey agreed well with cotinine, whereas ICD-10 codes did not. Clinical reminders could be used in other health systems to capture more accurate smoking information.

Conclusions

Clinical reminders are an excellent source for self-reported smoking status and are readily available in the VHA EHR.
Feeding a high-energy finishing diet upon arrival to high-risk feedlot calves: effects on health, performance, ruminal pH, rumination, serum metabolites, and carcass traits
Authors: Crawford David M , Richeson John T , Perkins Thomas L , Samuelson Kendall L
Published: May 2022

This study evaluated the impacts of feeding a high-energy finishing diet during both the receiving and finishing period compared with a lower-energy receiving diet with adaptation to the finishing diet on health, performance, serum chemistry, ruminal pH, rumination, and carcass characteristics of high-risk feedlot cattle. Five truck-load blocks of steers (n = 101) and bulls (n = 299) were used in a generalized complete block design and randomly assigned to receive: 1) finishing diet for the entire feeding period (FIN) or 2) receiving diet for the first 56 d, followed by a transition to the finishing diet (REC). All cattle were fed ad libitum and consumed the same diet by day 74. A subset of cattle (n = 48) was randomly selected to quantify ruminal pH, temperature, and rumination time. Ultrasound images were collected on days 0, 74, and 146 to determine fat thickness over the 12th rib and rump, and carcass characteristics were determined after slaughter. Cattle fed FIN had less (P < 0.01) dry matter intake (DMI) from days 0 to 74, but DMI did not differ (P = 0.80) after day 74. From days 0 to final, DMI was 0.26 kg less for FIN compared with REC (P = 0.01). However, calculated metabolizable energy intake was not different from days 0 to 74 (P = 0.19), days 74 to final (P = 0.80), or overall (P = 0.78). Body weight (BW) on day 74 was greater (P < 0.01) and final BW tended to be greater (P = 0.10) for FIN compared with REC. Cattle consuming FIN had greater (P < 0.01) average daily gain and increased (P < 0.01) gain:feed from days 0 to 74. There were no differences (P ≥ 0.31) in health outcomes. On day 74, FIN had greater (P = 0.04) fat thickness over the rump and rib but did not differ (P ≥ 0.52) on day 146. Carcasses of FIN had greater (P = 0.04) hot carcass weight with no difference (P ≥ 0.11) in ribeye area, 12th rib fat thickness, yield grade, or quality grade. There was no difference (P = 0.18) in liver abscess rate. There was a diet × day interaction for blood urea nitrogen (P = 0.02) such that concentration decreased from days 0 to 28 in both treatments, but was less on day 28 for FIN. Ruminal pH was greater on days 2 and 61 and rumination time was less from days 0 to 28 for FIN (diet × day interaction; P < 0.01). Overall, these results suggest that providing a finishing diet fed ad libitum to high-risk calves upon arrival may be a viable alternative to a low-energy receiving diet.
Same Same but Different? Why War-Sustaining Objects Can Be Destroyed but Not Targeted
Authors: Reetz Niklas S
Published: May 2022

Fighting wars is expensive. Parties to an armed conflict therefore face incentives to take military action against an enemy’s ability to finance warfare. Disputes about the lawfulness of targeting economic objects that contribute to an adversary’s war-sustaining capability reach back as far as the American Civil War. The debate has recently regained attention with conflicts such as the fight against ISIS, where the international coalition carried out attacks against oil fields and money depots. In contrast to the argument of military necessity that states and scholars raise in favour of a broad interpretation of the definition of military objectives, this article finds that the purpose and extraordinary structure of Article 52(2) of Additional Protocol I to the Geneva Conventions preclude the targeting of war-sustaining economic objects. The article then explores a different, less-discussed mode of action against war-sustaining objects, namely their destruction. The so-called ‘cotton claims’ of the American Civil War are often invoked as a historical example of the lawful targeting of economic objects. A close analysis, however, shows that the facts underlying the cotton claims differ categorically from modern targeting practice. At the same time, the analysis reveals destruction as a potentially lawful alternative mode of action against economic objects. The cotton claims ultimately demonstrate that the destruction of economic objects outside the context of an attack can reconcile the argument of military necessity with the protection of civilian life, which is an insight equally relevant for modern warfare.
Bayesian methods for ancestral state reconstruction in morphosyntax: Exploring the history of argument marking strategies in a large language family
Authors: Phillips Joshua , Bowern Claire
Published: May 2022

Bayesian phylogenetic methods have been gaining traction and currency in historical linguistics, as their potential for uncovering elements of language change is increasingly understood. Here, we demonstrate a proof of concept for using ancestral state reconstruction methods to reconstruct changes in morphology. We use a simple Brownian motion model of character evolution to test how splits in ergative marking evolve across Pama-Nyungan, a large family of Australian languages. We are able to recover linguistically plausible paths of change, as well as rejecting implausible paths. The results of these analyses elucidate constraints on changes that have led to extensive synchronic variation in an interlocking morphological system. They further provide evidence of an ergative–accusative split traceable to Proto-Pama-Nyungan.
A nationwide prospective cohort study on safety of the 17D-204 yellow fever vaccine during a vaccine shortage in Japan
Authors: Miyazato Yusuke , Terada Mari , Ujiie Mugen , Saito Sho , Moriya Akinari , Ando Masao , Ohmagari Norio
Published: May 2022

In response to the vaccine shortage of yellow fever vaccine (YF-VAX) due to manufacturing delays, the unapproved 17D-204 YF-VAX was used as an investigator-initiated clinical trial in Japan. The vaccine was administered to 11 279 participants in 19 YF vaccination centres in Japan, and few serious adverse events were observed.
Humbug and a ‘Welsh Hindoo’: A Small History of Begging, Race and Language in Mid-nineteenth Century Liverpool
Authors: Johnes Martin
Published: May 2022

In 1849, a Liverpool newspaper printed a letter about an encounter with a lascar who was selling hymn sheets. The same newspaper had recently reported the arrest of someone similar for drunkenness and the letter writer, a migrant from Wales, confronted the hymn seller angrily in Welsh. To his surprise, the man responded in the same language and eventually confessed to being from Anglesey rather than Bombay. Much about the incident is unclear. Had the hymn seller coloured his skin? Why did he regard passing as an Indian as a useful sales technique? Why was the letter writer angry and why did he confront the man in Welsh? Did the incident even happen? Attempting to answer such questions can provide pointers to much wider historical issues. A ‘small history’ of this incident offers an opportunity to explore the dynamics of class, language and race in the middle of the nineteenth century. The incident reveals the anxieties the middle classes had around their position and whether their goodwill was being exploited by the poor. It points towards the impact of racism on people of colour and the significance of ethnicity for white migrants too. The incident also illustrates how the working classes and people of colour were not without agency, however they were thought about by those whose attitudes and power shaped their lives. Yet all these interpretations rest on a degree of supposition and the article concludes that historians too can engage in a degree of deception in their writings.
PHACT: Phylogeny-Aware Computing of Tolerance for Missense Mutations
Authors: Kuru Nurdan , Dereli Onur , Akkoyun Emrah , Bircan Aylin , Tastan Oznur , Adebali Ogun
Published: May 2022

Evolutionary conservation is a fundamental resource for predicting the substitutability of amino acids and the loss of function in proteins. The use of multiple sequence alignment alone—without considering the evolutionary relationships among sequences—results in the redundant counting of evolutionarily related alteration events, as if they were independent. Here, we propose a new method, PHACT, that predicts the pathogenicity of missense mutations directly from the phylogenetic tree of proteins. PHACT travels through the nodes of the phylogenetic tree and evaluates the deleteriousness of a substitution based on the probability differences of ancestral amino acids between neighboring nodes in the tree. Moreover, PHACT assigns weights to each node in the tree based on their distance to the query organism. For each potential amino acid substitution, the algorithm generates a score that is used to calculate the effect of substitution on protein function. To analyze the predictive performance of PHACT, we performed various experiments over the subsets of two datasets that include 3,023 proteins and 61,662 variants in total. The experiments demonstrated that our method outperformed the widely used pathogenicity prediction tools (i.e., SIFT and PolyPhen-2) and achieved a better predictive performance than other conventional statistical approaches presented in dbNSFP. The PHACT source code is available at https://github.com/CompGenomeLab/PHACT.
Standard clinical approaches and emerging modalities for glioblastoma imaging
Authors: Bernstock Joshua D , Gary Sam E , Klinger Neil , Valdes Pablo A , Ibn Essayed Walid , Olsen Hannah E , Chagoya Gustavo , Elsayed Galal , Yamashita Daisuke , Schuss Patrick , Gessler Florian A , Paolo Peruzzi Pier , Bag Asim K , Friedman Gregory K
Published: May 2022

Glioblastoma (GBM) is the most common primary adult intracranial malignancy and carries a dismal prognosis despite an aggressive multimodal treatment regimen that consists of surgical resection, radiation, and adjuvant chemotherapy. Radiographic evaluation, largely informed by magnetic resonance imaging (MRI), is a critical component of initial diagnosis, surgical planning, and post-treatment monitoring. However, conventional MRI does not provide information regarding tumor microvasculature, necrosis, or neoangiogenesis. In addition, traditional MRI imaging can be further confounded by treatment-related effects such as pseudoprogression, radiation necrosis, and/or pseudoresponse(s) that preclude clinicians from making fully informed decisions when structuring a therapeutic approach. A myriad of novel imaging modalities have been developed to address these deficits. Herein, we provide a clinically oriented review of standard techniques for imaging GBM and highlight emerging technologies utilized in disease characterization and therapeutic development.
Combination Therapy With Casirivimab/Imdevimab and Remdesivir for Protracted SARS-CoV-2 Infection in B-cell-Depleted Patients
Authors: Dioverti M Veronica , Gaston David C , Morris C Paul , Huff Carol Ann , Jain Tania , Jones Richard , Anders Viki , Lederman Howard , Saunders Jacqueline , Mostafa Heba H , Avery Robin K
Published: May 2022

Profoundly B-cell-depleted patients can have prolonged severe acute respiratory syndrome coronavirus 2 infections with evidence of active viral replication, due to inability to mount an adequate humoral response to clear the virus. We present 3 B-cell-depleted patients with prolonged coronavirus disease 2019 infection who were successfully treated with a combination of casirivimab/imdevimab and remdesivir.
Patient triage to specialist outpatient clinics—time to standardize terminology
Authors: Belostotsky Vladimir , Roy Madan , Mikrogianakis Angelo
Published: May 2022

Objectives

The objectives of this study were to evaluate existing nomenclature used for outpatient referrals triage and propose a system, which meets the needs of McMaster Children’s Hospital and can be modified for use in other hospitals.

Methods

We reviewed triage practices in the Department of Pediatrics, McMaster Children Hospital, Hamilton, Ontario and conducted a literature search to assess terminology used for outpatient referrals triage at other institutions.

Results

There is lack of unified terminology for triaging outpatient referrals. Existing systems are not widely accepted, lack uniformity, and often miss recording the true acuity of the referral. We developed a system that covers most outpatient triage scenarios, allocates either flexible or precise visit timelines to referrals and plans for logistics of the patient’s visit. Triage categories are iMMediate (MM), Acute (A) (1 to 14 days), Semi-Acute (S) (1 to 3 months), Timetabled (T) (next available appointment slot), Evaluated (E) (used for either forwarding to another provider or requesting additional information), and Rejected (R) categories—McMASTER triage system. Several numbered subcategories are used in each category to define precise timelines, if needed. Visit logistics categories are the following: Hub (H) (place to see the patient), How to notify patient and referring provider (HP) and (HD), need to Start with tests prior to appointment (S), and need to Complete (C) other relevant local processes—HHSC logistics system. Both these systems may be adapted for local use in other institutions.

Conclusion

This is the first publication that proposes terminology standardization in triaging outpatient referrals for specialist paediatric services.
Ustilaginoidea virens secretes a family of phosphatases that stabilize the negative immune regulator OsMPK6 and suppress plant immunity
Authors: Zheng Xinhang , Fang Anfei , Qiu Shanshan , Zhao Guosheng , Wang Jiyang , Wang Shanzhi , Wei Junjun , Gao Han , Yang Jiyun , Mou Baohui , Cui Fuhao , Zhang Jie , Liu Jun , Sun Wenxian
Published: May 2022

Rice false smut caused by Ustilaginoidea virens is emerging as a devastating disease of rice (Oryza sativa) worldwide; however, the molecular mechanisms underlying U. virens virulence and pathogenicity remain largely unknown. Here we demonstrate that the small cysteine-rich secreted protein SCRE6 in U. virens is translocated into host cells during infection as a virulence factor. Knockout of SCRE6 leads to attenuated U. virens virulence to rice. SCRE6 and its homologs in U. virens function as a novel family of mitogen-activated protein kinase phosphatases harboring no canonical phosphatase motif. SCRE6 interacts with and dephosphorylates the negative immune regulator OsMPK6 in rice, thus enhancing its stability and suppressing plant immunity. Ectopic expression of SCRE6 in transgenic rice promotes pathogen infection by suppressing the host immune responses. Our results reveal a previously unidentified fungal infection strategy in which the pathogen deploys a family of tyrosine phosphatases to stabilize a negative immune regulator in the host plant to facilitate its infection.
Ethylene augments root hypoxia tolerance via growth cessation and reactive oxygen species amelioration
Authors: Liu Zeguang , Hartman Sjon , van Veen Hans , Zhang Hongtao , Leeggangers Hendrika A C F , Martopawiro Shanice , Bosman Femke , de Deugd Florian , Su Peng , Hummel Maureen , Rankenberg Tom , Hassall Kirsty L , Bailey-Serres Julia , Theodoulou Frederica L , Voesenek Laurentius A C J , Sasidharan Rashmi
Published: May 2022

Flooded plants experience impaired gas diffusion underwater, leading to oxygen deprivation (hypoxia). The volatile plant hormone ethylene is rapidly trapped in submerged plant cells and is instrumental for enhanced hypoxia acclimation. However, the precise mechanisms underpinning ethylene-enhanced hypoxia survival remain unclear. We studied the effect of ethylene pretreatment on hypoxia survival of Arabidopsis (Arabidopsis thaliana) primary root tips. Both hypoxia itself and re-oxygenation following hypoxia are highly damaging to root tip cells, and ethylene pretreatments reduced this damage. Ethylene pretreatment alone altered the abundance of transcripts and proteins involved in hypoxia responses, root growth, translation, and reactive oxygen species (ROS) homeostasis. Through imaging and manipulating ROS abundance in planta, we demonstrated that ethylene limited excessive ROS formation during hypoxia and subsequent re-oxygenation and improved oxidative stress survival in a PHYTOGLOBIN1-dependent manner. In addition, we showed that root growth cessation via ethylene and auxin occurred rapidly and that this quiescence behavior contributed to enhanced hypoxia tolerance. Collectively, our results show that the early flooding signal ethylene modulates a variety of processes that all contribute to hypoxia survival.
Auxin-driven ecophysiological diversification of leaves in domesticated tomato
Authors: Moreira Juliene d R , Rosa Bruno L , Lira Bruno S , Lima Joni E , Correia Ludmila N F , Otoni Wagner C , Figueira Antonio , Freschi Luciano , Sakamoto Tetsu , Peres Lázaro E P , Rossi Magdalena , Zsögön Agustin
Published: May 2022

Heterobaric leaves have bundle sheath extensions (BSEs) that compartmentalize the parenchyma, whereas homobaric leaves do not. The presence of BSEs affects leaf hydraulics and photosynthetic rate. The tomato (Solanum lycopersicum) obscuravenosa (obv) mutant lacks BSEs. Here, we identify the obv gene and the causative mutation, a nonsynonymous amino acid change that disrupts a C2H2 zinc finger motif in a putative transcription factor. This mutation exists as a polymorphism in the natural range of wild tomatoes but has increased in frequency in domesticated tomatoes, suggesting that the latter diversified into heterobaric and homobaric leaf types. The obv mutant displays reduced vein density, leaf hydraulic conductance and photosynthetic assimilation rate. We show that these and other pleiotropic effects on plant development, including changes in leaf insertion angle, leaf margin serration, minor vein density, and fruit shape, are controlled by OBV via changes in auxin signaling. Loss of function of the transcriptional regulator AUXIN RESPONSE FACTOR 4 (ARF4) also results in defective BSE development, revealing an additional component of a genetic module controlling aspects of leaf development important for ecological adaptation and subject to breeding selection.
0002 Go to bed! A systematic review and meta-analysis of bedtime procrastination determinants and sleep outcomes
Authors: Hill Vanessa , Ferguson Sally , Rebar Amanda , Shriane Alexandra , Vincent Grace
Published: May 2022

Introduction

Bedtime procrastination, the volitional delay of going to bed without any external circumstances causing the delay, is associated with poor sleep outcomes. Alleviating bedtime procrastination is an important target for interventions to promote adequate sleep, yet the social cognitive, biological, and behavioural determinants of bedtime procrastination are poorly understood. The present study aimed to conduct a systematic review, narrative synthesis, and meta-analysis of (1) the underlying determinants of bedtime procrastination, and (2) the strength and direction of the relationship between bedtime procrastination and sleep outcomes.

Methods

A database search was conducted through CINAHL, EMBASE, PsychINFO, PubMed, Scopus and Web of Science, using keywords related to procrastination, delay, bedtime and sleep.

Results

A total of 2087 records were identified, and 38 publications met the inclusion criteria. Random-effects meta-analysis for bedtime procrastination and sleep outcomes is ongoing. Preliminary findings suggest self-regulation, self-control and chronotype are the most prominent determinants.

Conclusion

Future research should expand focus to identify a broader range of determinants. Given that there are multiple benefits to a theory-based approach to behaviour change interventions, further research exploring determinants will be able to guide the development of interventions targeting bedtime procrastination.

Support (If Any):
0003 On the Same Wavelength? Quantifying the Associations between Eating Timing and Rest-Activity Rhythms in Free-Living Adults
Authors: Hoopes Elissa , D'Agata Michele , Brookstein-Burke Talia , Robson Shannon , Witman Melissa , Malone Susan , Patterson Freda
Published: May 2022

Introduction

Misalignment between the central circadian clock and daily behaviors increases cardiometabolic morbidity and mortality risk, likely due to internal misalignment between central and peripheral circadian rhythms. Experimental studies suggest food intake may act as a time cue (‘zeitgeber’) for resetting circadian rhythms, representing a potential behavioral target to ameliorate circadian misalignment and associated health consequences. However, the extent to which eating timing relates to circadian rhythms in free-living adults is unclear. Therefore, we tested the associations between eating timing with 24-h rest-activity-rhythms (RAR), a free-living proxy for endogenous circadian rhythms, in non-shift-working adults.

Methods

Adults without chronic health conditions or sleep disorders completed 14 days of 24/7 wrist accelerometry to evaluate RAR variables of interdaily stability (IS; day-to-day stability in RAR), intradaily variability (IV; within-day fragmentation of RAR), relative amplitude (RA; difference between peak vs. trough activity), L5 onset time (5-h period with lowest activity), and M10 onset time (10-h period with highest activity). Concurrently, time-stamped image-assisted diet records were obtained to generate average eating timing variables, including daily eating onset (time of first caloric intake after awakening), offset (last caloric intake time), duration (time elapsed between eating onset and offset), and caloric midpoint (time at which 50% of daily kcals were consumed), and variables illustrating irregularity in eating timing (standard deviation of eating timing variables). Pearson’s correlations quantified the associations between RAR and eating timing variables.

Results

Participants (N=30) were 28.0±6.6 years, 57% female, with a BMI of 23.8±2.5 kg/m2. Higher IS was correlated with lower irregularity in both eating onset (r=-0.55, p<0.01) and duration (r=-0.51, p<0.01). Higher RA correlated with earlier eating onset (r=-0.47, p<0.01), longer eating duration (r=0.53, p<0.01), and lower eating onset irregularity (r=-0.37, p<0.05). Later L5 correlated with later eating onset (r=0.67, p<0.001), offset (r=0.58, p<0.001), caloric midpoint (r=0.56, p<0.01), and greater eating offset irregularity (r=0.53, p<0.01). Later M10 correlated with later eating offset (r=0.40, p<0.05).

Conclusion

Preliminary findings indicate that eating timing and RAR are moderately correlated in free-living adults. Earlier eating timing, increased eating regularity, and longer daily eating duration may represent behavioral targets for improving circadian rhythms and subsequent cardiometabolic outcomes.

Support (If Any): Support provided by the American Heart Association (#831488) and a University of Delaware Research Fund-Strategic Initiative Award.
0004 Sleep, Team and Social Processes, and Health, Performance, and Safety in Naval Operational Environments
Authors: Roma Peter , Jameson Jason , Kubala Andrew , Markwald Rachel , Russell Dale
Published: May 2022

Introduction

Sleep disruption and teamwork are inherent features of 24/7 operational environments, yet little is known about how sleep and team/social processes interact to affect crew readiness and endurance.

Methods

We analyzed data of 3,434 active duty US sailors (80% male) from the Afloat Safety Climate Assessment Survey. Using structural equation modeling, we specified latent factors of Sleep Health (typical hours of sleep per day and sleep disturbances in shipboard environment); crew team and social factors of Team Transition Processes, Team Action Processes, Team Interpersonal Processes, Unit Cohesion, Psychological Safety, and Social Support; and operational outcome risks of Physical Health (no. days in previous 30 with physical illness or injury), Mental Health (no. days with stress, depression, or emotional problems), Performance (frequency of fatigue-induced functional impairments on duty), and Safety (individual and crew noncompliance, and rate of observed near misses).

Results

Higher Sleep Health reduced impairments in Physical Health, Mental Health, Performance, and Safety (standardized βs = −0.096 to −0.542, ps < 0.0001, CFI/TLI > 0.980, RMSEA = 0.033). Higher Sleep Health improved Team Transition, Action, and Interpersonal Processes, Unit Cohesion, Psychological Safety, and Social Support (βs = 0.178 to 0.380, ps < 0.0001, CFI/TLI > 0.982, RMSEA = 0.029). Social Support reduced risks to Physical Health, Mental Health, and Performance; Team Interpersonal Processes reduced Metal Health risk; Psychological Safety reduced Performance and Safety risks; Unit Cohesion reduced Safety risk (βs = −0.053 to −0.709, ps < 0.05, CFI/TLI > 0.979, RMSEA = 0.027). Mediation models indicated good Sleep Health enhances Social Support’s beneficial impact on Physical Health, Mental Health, and Performance; Psychological Safety’s impact on Performance and Safety; Team Interpersonal Processes’ impact on Physical Health; and Unit Cohesion’s impact on Safety (indirect effect βs = −0.032 to −0.127, ps < 0.0001, CFI/TLI > 0.967, RMSEAs < 0.051).

Conclusion

Sleep health improves team/social functioning, which serves an additive protective function and enhancement to crew operational health, performance, and safety. Future work should closely examine these interrelationships to identify mechanisms as targets for policy and procedures to help optimize crew readiness and endurance.

Support (If Any)

Military Operational Medicine Research Program under work unit N2010.
0006 An At-Home Evaluation of a Light Intervention to Mitigate Sleep Inertia Symptoms
Authors: Hilditch Cassie , Costedoat Gregory , Pradhan Sean , Bathurst Nicholas , Glaros Zachary , Gregory Kevin , Feick Nathan , Shattuck Nita , Flynn-Evans Erin
Published: May 2022

Introduction

Sleep inertia symptoms typically occur after waking from nocturnal sleep. Under laboratory settings, light exposure upon waking has been shown to improve alertness, mood, and vigilant attention. We investigated whether a field-deployable light-emitting device would help to improve alertness and working memory in a real-world setting.

Methods

Thirty-five participants (18 female; 26.4 ± 6.0 y) completed an at-home, within-subject, randomized crossover study. Participants wore actiwatches during their normal sleep-wake schedule for five nights ahead of the adaptation and experimental nights. On the experimental night, participants performed baseline testing before their self-selected bedtime. Forty-five minutes after bedtime, participants received a phone call and were instructed to perform test bouts while wearing light-emitting glasses with the light either on (light condition) or off (control). A 3-minute descending subtraction task (DST) and the Karolinska Sleepiness Scale (KSS) were performed at +7, +17, +27, and +37 minutes after the call. Participants were then instructed to go back to sleep and were called 45 minutes after lights out to repeat the test bouts in the opposite condition. A series of mixed-effects models were performed with fixed effects of condition, test bout, and their interaction, and a random effect of participant. Condition order, sex, and baseline were included as covariates.

Results

There was a significant effect of test bout for DST total responses (χ2 [3] = 17.42; p < .001) and total correct (χ2 [3] = 21.29; p < .001) with improved performance at +27 and +37 minutes compared to +7 minutes. Sex was a significant predictor for KSS (F1,30 = 10.26; p = .003), with females (8.20 ± 0.23) rating higher sleepiness than males (7.10 ± 0.25). There were no other significant effects for DST or KSS outcomes (p > .05).

Conclusion

These results suggest that the intervention was not able to improve working memory or alertness under naturalistic at-home settings. Further analysis is needed to determine whether these results are applicable to other cognitive performance domains.

Support (If Any)

Funded by the Naval Postgraduate School, via the Naval Medical Research Center's Naval Advanced Medical Development Department (MIPR N3239820WXHN007), with support from the NASA Airspace Operations and Safety Program, System-Wide Safety.
0009 Interindividual variation and extended wakefulness in sleepiness after acute and chronic sleep deprivation
Authors: Fernandes Guilherme , Araujo Paula , Tufik Sergio , Andersen Monica
Published: May 2022

Introduction

Sleepiness is a behavioural consequence of sleep pressure and is associated with negative outcomes with interindividual variation, possibly related to central sleep mechanisms. However, there is a lack of evidence linking progressive sleep need and sleepiness with factors of individual variability, which could be tested by total acute and chronic sleep deprivation. Thus, the objective of the study was to investigate the development of sleepiness in sleep deprived mice.

Methods

Male C57BL/6J mice were distributed in sleep deprivation, sleep rebound and control groups. Animals underwent acute sleep deprivation for 3, 6, 9 or 12 hours or chronic sleep deprivation for 6 hours for 5 consecutive days. Sleep rebound groups had a sleep opportunity for 1, 2, 3, or 4 hours after acute sleep deprivation or 24 hours after chronic sleep deprivation. During the protocols, sleep attempts were counted to calculate a sleepiness index. After euthanasia, blood was collected for corticosterone assessment.

Results

Using the average of group sleep attempts, it was possible to differentiate between sleepy (mean>group average) and resistant animals (mean<group average). Resistant mice were more frequent in all settings. Individual variation accounted for 52% of sleepiness variance during chronic sleep deprivation and extended wakefulness explained 68% of sleepiness variance during acute sleep deprivation. A normal corticosterone peak was observed at the start of the dark phase, independent of sleep deprivation.

Conclusion

Different profiles of sleepiness emerged in sleep deprived mice. Sleep deprivation was the main factor for sleepiness during acute sleep deprivation whereas in chronic deprivation individual variation was more relevant.

Support (If Any)

Our studies are supported by the following funding agencies: AFIP (Associação Fundo de Incentivo à Pesquisa), São Paulo Research Foundation (FAPESP #2017/18455-5 to GLF), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brasil (CAPES - Finance Code 001 to GLF), and CNPq (fellowships to MLA and ST; #169040/2017-8, and #141445/2021-1 to GLF). This study received indirect funding from AFIP and CNPq, which support the department in which the project was conducted.
0020 Investigation of Seasonal Changes in Self-Reported Sleep Quality and Psychomotor Vigilance Task Outcomes: Results From the Ultra Long-Term Sleep (ULTS) Study
Authors: Ahrens Esben , Hemmsen Martin Christian , Duun-Henriksen Jonas , Kjær Troels Wesenberg , Allen Luke , Cormack Francesca , Taptiklis Nick
Published: May 2022

Introduction

Although sleep is fundamental for human well-being, factors that contribute to an individual’s experience and report of sleep quality remain poorly understood. Utilizing that sleepiness is known to impact vigilance performance, this study sets out to explore how self-reported sleep quality changes with behavioral performance and how this variation is affected by seasonal changes.

Methods

This work is an interim analysis of self-reported sleep quality and behavioral performance data collected in the Ultra Long-term Sleep (ULTS) study (ClinicalTrials.gov Identifier: NCT04513743). In the study 20 healthy participants (average 33±13 years of age) were enrolled for 365 continuous days to observe the seasonal variation in sleep and cognitive performance. The outcome from the daily psychomotor vigilance task (PVT) and sleep questionnaire is analyzed and reported. The sleep questionnaire is a composite of questions from the Sleep Satisfaction Tool, the Karolinska Sleep Diary, questions regarding feelings of pain and outside disturbances, easiness of waking up, and the Karolinska Sleepiness Scale (KSS). The PVT was designed for self-administered high-frequency testing and has a short 3-minute test period. Monthly changes were examined from June to November. This period was chosen since all subjects were active.

Results

The first eight participants have now completed the study. Repeated measures correlations between KSS and mean PVT reaction time showed moderate but highly robust associations between the two measures over time (r=0.2; 95% CI 0.18-0.23). From the data collected thus far from the entire population, fastest PVT mean reaction times were found on Saturdays and slowest on Tuesdays. Similarly, KSS had best scores in weekends. There was an overall increase in mean PVT reaction time during the investigated period from June to November. This was also observed in KSS.

Conclusion

Our findings show a moderate correlation between the mean PVT reaction time and Karolinska Sleepiness Scale with up to 365 datapoints per subject with weekly and seasonal trends observed.

Support (If Any)

This research is supported by Innovation Fund Denmark.