bluuebunny/crossref_metadata_2025 huggingface dataset:
Sociohistorical Change in Urban Older Adults’ Perceived Speed of Time and Time Pressure
Authors: Löckenhoff Corinna E , Drewelies Johanna , Duezel Sandra , Steinhagen-Thiessen Elisabeth , Demuth Ilja , Freund Alexandra M , Staudinger Ursula M , Lindenberger Ulman , Wagner Gert G , Ram Nilam , Gerstorf Denis
Published: May 2021

Objectives

Perceptions of time are shaped by sociohistorical factors. Specifically, economic growth and modernization often engender a sense of acceleration. Research has primarily focused on one time perception dimension (perceived time pressure) in one subpopulation (working-age adults), but it is not clear whether historical changes extend to other dimensions (e.g., perceived speed of time) and other subpopulations, such as older adults who are no longer in the workforce and experience age-related shifts in time perception. We therefore examined sociohistorical and age-related trends in two dimensions of time perception in two cohorts of urban older adults.

Method

Using propensity score matching for age and education, samples were drawn from the Berlin Aging Study (1990–1993, n = 256, Mage = 77.49) and the Berlin Aging Study-II (2009–2014, n = 248, Mage = 77.49). Cohort differences in means, variances, covariance, and correlates of perceived speed of time and time pressure were examined using multigroup SEM.

Results

There were no cohort differences in the perceived speed of time, but later-born cohorts reported more time pressure than earlier-born cohorts. There were no significant age differences, but perceptions of speed of time were more heterogeneous in the 1990s than in the 2010s. Cohorts did not differ in how time perceptions were associated with sociodemographic, health, cognitive, and psychosocial correlates.

Discussion

These findings document sociohistorical trends toward greater perceived time pressure and reduced heterogeneity in perceived speed of time among later-born urban adults. Conceptualizations of social acceleration should thus consider the whole adult life span.
Economic and Social Rights, Reparations and the Aftermath of Widespread Violence: The African Human Rights System and Beyond
Authors: Torres Felix E
Published: May 2021

This article examines the dual responsibility of state authorities to repair past abuses and guarantee economic and social rights after episodes of widespread violence according to the jurisprudence of African human rights bodies. Two alternative frameworks underlying the practice of African bodies and human rights law more broadly are discussed. The first portrays the state as a threat to the individual, responsible for redressing the consequences of violations in breach of duties to respect and protect rights. The second understands the state as an active guarantor of rights in the aftermath of widespread abuses, responsible for improving the well-being of people affected and not affected by violence. In light of the possibilities and limitations that arise from both approaches in the African context, the article advocates the second.
The Epigenome and Beyond: How Does Non-genetic Inheritance Change Our View of Evolution?
Authors: Brodie Edmund D , Gregory Brian , Lisch Damon , Riddle Nicole C
Published: May 2021

Synopsis

Evidence from across the tree of life suggests that epigenetic inheritance is more common than previously thought. If epigenetic inheritance is indeed as common as the data suggest, this finding has potentially important implications for evolutionary theory and our understanding of how evolution and adaptation progress. However, we currently lack an understanding of how common various epigenetic inheritance types are, and how they impact phenotypes. In this perspective, we review the open questions that need to be addressed to fully integrate epigenetic inheritance into evolutionary theory and to develop reliable predictive models for phenotypic evolution. We posit that addressing these challenges will require the collaboration of biologists from different disciplines and a focus on the exploration of data and phenomena without preconceived limits on potential mechanisms or outcomes.
Behaviour in a bottom trawl: moving forward to limit catches of Atlantic cod
Authors: Pol M , Eayrs S
Published: May 2021

The iconic Atlantic cod (Gadus morhua Linnaeus, 1758) has inspired a substantial body of fishing-gear research across its geographical range, with recent efforts predominately to reduce catches of this species in fisheries where their populations are fragile. Despite their iconic status and long history of study compared to other species, our understanding of cod behaviour during the capture process in a bottom trawl remains frustratingly limited. Much of our understanding is derived indirectly through catch results, supported to a limited extent by direct observations of cod in situ or held in laboratories. In this paper, we describe four research challenges and directions that we consider critical to advance our knowledge of cod behaviour, and ultimately, to improve the selectivity of bottom trawls to reduce catches of cod. These include the resurrection of behavioural research to directly observe and measure their reaction and sensory capabilities, and improved interpretation of their behaviour in response to a bottom trawl. It is also our view that progress in limiting catches of cod should emphasize stimulating avoidance in advance or at the mouth of an approaching bottom trawl, rather than retrospectively attempting to do so after they have entered the trawl mouth.
Respiratory Viral Infections and Infection Prevention Practices Among Women With Acute Respiratory Illness During Delivery Hospitalizations During the 2019–2020 Influenza Season
Authors: Dawood Fatimah S , Varner Michael , Munoz Flor , Stockwell Melissa S , Suyama Joe , Li De-Kun , Tita Alan , Mathias Leigh , Shakib Julie H , Piedra Pedro A , Gyamfi-Bannerman Cynthia , Weissman Alexandra , Ferber Jeannette , Battarbee Ashley N , Wesley Meredith G , Vorwaller Kelly , Powers Emily , Gibson Marie , Bond Nanette , Santarcangelo Patricia , Avadhanula Vasanthi , Newes-Adeyi Gabriella , Hunt Danielle Rentz , Subramaniam Akila , Sanusi Ayodeji , Boone Amy , Ogokeh Constance , Macio Ingrid , Odouli Roxana , Thind Priyam , Vargas Celibell Y , Almonte Casandra , Galang Romeo R , Shapiro-Mendoza Carrie , Campbell Angela P
Published: May 2021

Background

We conducted a cross-sectional study of pregnant women with acute respiratory illness during delivery hospitalizations during influenza season to describe clinical testing for respiratory viruses and infection prevention practices.

Methods

Women had nasal swabs tested for influenza and other respiratory viruses. Among 91 enrolled women, 22 (24%) had clinical testing for influenza.

Results

Based on clinical and study testing combined, 41 of 91 (45%) women had samples positive for respiratory viruses. The most common virus was influenza (17 of 91, 19%); 53% (9 of 17) of influenza virus infections were identified through study testing alone. Only 16% of women were on droplet precautions.

Conclusions

Peripartum respiratory infections may be underrecognized.
Ruminal degradation kinetics, intake, digestibility, and feeding behavior of beef steers offered annual or perennial grass-hay with or without supplementation
Authors: Sugg Joel D , Sarturi Jhones O , Henry Darren D , Ciriaco Francine M , West Charles P , Ballou Michael A , Hoffmann Carly A
Published: May 2021

Effects of dried distillers grains plus solubles (DDGS) on ruminal fermentation, degradation kinetics, and feeding behavior of steers offered annual (Eragrostis tef; TEFF) or perennial (Bothriochloa bladhii; OWB) grass hay were evaluated. Ruminally cannulated Angus crossbred steers (n = 6; body weight [BW] = 304 ± 11 kg) were assigned to a 4 × 6 unbalanced Latin square design with four treatments arranged as a 2 × 2 factorial: hay type (OWB or TEFF) and DDGS supplementation (0% or 0.5% BW [dry matter {DM} basis]). Steers had ad libitum access to hay. Periods consisted of a 14-d adaptation followed by 7 d of collection. Residues from the in situ incubations (0, 3, 6, 12, 24, 36, 48, 72, and 96 h post-feeding) were fitted to a first-order kinetics model using the NLIN procedure of SAS. The DDGS decreased (P < 0.01) TEFF DM intake (DMI) by 11.3%, while not affecting DMI of OWB. The greatest DMI was observed for steers supplemented with DDGS, regardless of forage, and least in steers consuming OWB without DDGS (hay type × DDGS; P = 0.03). Non-supplemented steers spent more (P < 0.01) time eating hay. Digestibility of DM tended (P = 0.06) to increase with DDGS supplementation. A hay type × DDGS interaction was observed (P ≤ 0.05) on ruminal effective degradable fractions. The rate of degradation, soluble fraction, and the potentially degradable fraction of organic matter (OM), neutral detergent fiber, and acid detergent fiber (ADF) increased (P ≤ 0.05), while the undegradable fraction of all components decreased (P ≤ 0.01) when steers were offered TEFF compared to OWB. Ruminal DM, OM, and ADF degradation lag-time increased (P ≤ 0.02) in steers offered OWB. Ruminal degradation kinetics were not (P ≥ 0.17) independently affected by DDGS supplementation. Average ruminal pH of steers offered TEFF (P < 0.01) and those offered DDGS (P < 0.01) were lower than OWB and non-supplemented steers. Total concentration of VFA tended (P = 0.09) to increase when DDGS was provided with OWB, while decreasing when TEFF was offered. The acetate:propionate increased (P < 0.01) with DDGS supplementation due to a decrease (P = 0.03) in propionate. Ruminal NH3-N was greater (P = 0.03) in steers offered TEFF compared to OWB, and those supplemented with DDGS (P = 0.03). An annual, in place of a conventional, perennial hay improved intake and digestion of nutrients, without affecting feeding behavior. The supplementation with DDGS appears to affect forage intake, ruminal degradation, and feeding behavior, although not independent of forage quality.
Comparative Efficacy of Commercial Liquid and Mat-Type Electric Vaporizer Insecticides Against Asian Tiger Mosquito (Diptera: Culicidae)
Authors: Jung Hun , An Huijun , Lee Minjin , Lee Jieun , Tak Jun-Hyung
Published: May 2021

Mat and liquid-type electric insecticide vaporizers continuously emit insecticides into the surrounding air. Because both the target insects, mostly mosquitoes, and humans are exposed to those insecticides, it is crucial to understand and monitor their deposition and spatial distribution in treated areas. In the current study, we examined the evaporation of insecticides from seven commercial liquid and mat vaporizers and measured their knock-down and insecticidal activity against the adult females of the Asian tiger mosquito, Aedes albopictus (Skuse). Electric vaporizers from three manufactures had differences in their heaters and active ingredients. Most had continued evaporation during hourly and daily monitoring; however, some liquid vaporizers failed to continue emission to their designated end periods. Overall, mosquitoes located at the upper position in a Peet-Grady chamber and in a field-simulation room exhibited faster knock-down activity than did mosquitoes in other areas, indicating that the insecticides accumulated on the ceiling area. Although most of mat and liquid vaporizers had <60 min of average KT90 values when tested in the Peet-Grady chamber (1.8 × 1.8 × 1.8 m), they failed to have any knock-down in 2 h of observation in the field-simulation room (6.8 × 3.4 × 2.7 m) but showed 72. 8 ± 11.7% and 56. 7 ± 7.3% knock-down in the mat and liquid vaporizers, respectively, in 3 h of operation. Further study will be required to examine whether this relatively limited efficacy can be compensated by other physiological and behavioral effects, including disruption in host-seeking or blood-sucking activities.
First Findings and Molecular Data of Phlebotomus mascittii (Diptera: Psychodidae) in the Cantabrian Cornice (Northern Spain)
Authors: Alarcón-Elbal P M , González M A , Delacour-Estrella S , Bravo-Barriga D , Estrada Peña R , Goiri F , García- Pérez A L , Lucientes J
Published: May 2021

Phlebotomus (Transphlebotomus) mascittii Grassi, 1908 (Diptera: Psychodidae) has been found in several European countries. In Spain, sporadic records were reported in the early ’80s in Catalonia (Northeast Spain), and it was never detected again. Recent entomological surveys carried out between 2004 and 2020 revealed the presence of several specimens of P. mascittii in Spain. The species identification was confirmed by both morphological and molecular analyses. The analyzed specimens belonged to the haplotype (COI_2) defined by one polymorphic site compared to other European specimens. Phlebotomus mascittii was found in low population densities in rural areas associated with livestock farms and in an urban cemetery during the summer season. This study provides the first records of this species in various localities along the Cantabrian cornice (Northern Spain) and represents its westernmost observation in the Palearctic region. The implications of the finding of this uncommon species are discussed at different levels, with emphasis on its suspected role in the transmission of leishmaniosis.
Relationship Between Caregiver Uncertainty, Problem-Solving, and Psychological Adjustment in Pediatric Cancer
Authors: Basile Nathan L , Chardon Marie L , Peugh James , Edwards Clayton S , Szulczewski Lauren , Morrison Caroline F , Nagarajan Rajaram , El-Sheikh Ayman , Chaney John M , Pai Ahna L H , Mullins Larry L
Published: May 2021

Objective

The current study examined the roles of constructive and dysfunctional problem-solving strategies in the relationships between illness uncertainty and adjustment outcomes (i.e., anxious, depressive, and posttraumatic stress symptoms) in caregivers of children newly diagnosed with cancer.

Methods

Two hundred thirty-eight caregivers of children (0–19 years of age) newly diagnosed with cancer (2–14 weeks since diagnosis) completed measures of illness uncertainty, problem-solving strategies, and symptoms of anxiety, depression, and posttraumatic stress.

Results

A mediation model path analysis assessed constructive and dysfunctional problem-solving strategies as mediators between illness uncertainty and caregiver anxious, depressive, and posttraumatic stress symptoms. Dysfunctional problem-solving scores partially mediated the relationships between illness uncertainty and anxious, depressive, and posttraumatic stress symptoms. Constructive problem-solving scores did not mediate these relationships.

Conclusions

The current findings suggest that illness uncertainty and dysfunctional problem-solving strategies, but not constructive problem-solving strategies, may play a key role in the adjustment of caregivers of children newly diagnosed with cancer. Interventions aimed at managing illness uncertainty and mitigating the impact of dysfunctional problem-solving strategies may promote psychological adjustment.
Liposarcoma of the pelvic fossa masquerading as hematoma: a rare case report and its surgical management
Authors: Zarokosta Maria , Foutsitzi Aikaterini , Roditis Spyridon , Karanasiou Vasilissa , Nannou Eirini , Mariolis-Sapsakos Theodoros
Published: May 2021

Liposarcomas constitute rare malignant tumors of the soft tissue, with wide anatomical distribution. The prompt diagnosis of a liposarcoma is extremely challenging since these tumors tend to remain asymptomatic, until they grow enough to displace adjacent anatomical structures. In the presented case, a 55-year-old Caucasian male proceeded to our institution complaining about irreducible swelling of the right iliac fossa and constant discomfort, over the course of a year. His medical history revealed injury of the right groin and pelvis a year ago. The diagnosis was ilioinguinal liposarcoma masquerading as hematoma, due to the previous injury. The patient underwent primary complete tumor resection, and the operation was uneventful. The essential diagnostic and surgical steps for the management of a liposarcoma, mimicking a hematoma are meticulously described.
Regulation of alternative splicing in response to temperature variation in plants
Authors: John Sheeba , Olas Justyna Jadwiga , Mueller-Roeber Bernd
Published: May 2021

Plants have evolved numerous molecular strategies to cope with perturbations in environmental temperature, and to adjust growth and physiology to limit the negative effects of extreme temperature. One of the strategies involves alternative splicing of primary transcripts to encode alternative protein products or transcript variants destined for degradation by nonsense-mediated decay. Here, we review how changes in environmental temperature—cold, heat, and moderate alterations in temperature—affect alternative splicing in plants, including crops. We present examples of the mode of action of various temperature-induced splice variants and discuss how these alternative splicing events enable favourable plant responses to altered temperatures. Finally, we point out unanswered questions that should be addressed to fully utilize the endogenous mechanisms in plants to adjust their growth to environmental temperature. We also indicate how this knowledge might be used to enhance crop productivity in the future.
ANT and AIL6: masters of the master regulators during flower development
Authors: Juárez-Corona Ángela G , de Folter Stefan
Published: May 2021

This article comments on:

Krizek BA, Bantle AT, Heflin JM, Han H, Freese NH, Loraine AE. 2021. AINTEGUMENTA and AINTEGUMENTA-LIKE6 directly regulate floral homeotic, growth, and vascular development genes in young Arabidopsis flowers. Journal of Experimental Botany 72, 5478–5493.
Evolutionary and biochemical characterization of a Chromochloris zofingiensis MBOAT with wax synthase and diacylglycerol acyltransferase activity
Authors: Xu Yang , Pan Xue , Lu Junhao , Wang Juli , Shan Qiyuan , Stout Jake , Chen Guanqun
Published: May 2021

Wax synthase (WS) catalyzes the last step in wax ester biosynthesis in green plants. Two unrelated sub-families of WS, including the bifunctional acyltransferase and plant-like WS have been reported, but the latter is largely uncharacterized in microalgae. Here, we functionally characterized a putative plant-like WS (CzWS1) from the emerging model green microalga Chromochloris zofingiensis. Our results showed that plant-like WS evolved under different selection constraints in plants and microalgae, with positive selection likely contributing to functional divergence. Unlike jojoba with high amounts of wax ester in seeds and a highly active WS enzyme, C. zofingiensis has no detectable wax ester but a high abundance of WS transcripts. Co-expression analysis showed that C. zofingiensis WS has different expression correlation with lipid biosynthetic genes from jojoba, and may have a divergent function. In vitro characterization indicated that CzWS1 had diacylglycerol acyltransferase activity along with WS activity, and overexpression of CzWS1 in yeast and Chlamydomonas reinhardtii affected triacylglycerol accumulation. Moreover, biochemical and bioinformatic analyses revealed the relevance of the C-terminal region of CzWS1 in enzyme function. Taken together, our results indicated a functional divergence of plant-like WS in plants and microalgae, and the importance of its C-terminal region in specialization of enzyme function.
Sphingolipid Δ4-desaturation is an important metabolic step for glycosylceramide formation in Physcomitrium patens
Authors: Gömann Jasmin , Herrfurth Cornelia , Zienkiewicz Krzysztof , Haslam Tegan M , Feussner Ivo
Published: May 2021

Glycosylceramides are abundant membrane components in vascular plants and are associated with cell differentiation, organogenesis, and protein secretion. Long-chain base (LCB) Δ4-desaturation is an important structural feature for metabolic channeling of sphingolipids into glycosylceramide formation in plants and fungi. In Arabidopsis thaliana, LCB Δ4-unsaturated glycosylceramides are restricted to pollen and floral tissue, indicating that LCB Δ4-desaturation has a less important overall physiological role in A. thaliana. In the bryophyte Physcomitrium patens, LCB Δ4-desaturation is a feature of the most abundant glycosylceramides of the gametophyte generation. Metabolic changes in the P. patens null mutants for the sphingolipid Δ4-desaturase (PpSD4D) and the glycosylceramide synthase (PpGCS), sd4d-1 and gcs-1, were determined by ultra-performance liquid chromatography coupled with nanoelectrospray ionization and triple quadrupole tandem mass spectrometry analysis. sd4d-1 plants lacked unsaturated LCBs and the most abundant glycosylceramides. gcs-1 plants lacked all glycosylceramides and accumulated hydroxyceramides. While sd4d-1 plants mostly resembled wild-type plants, gcs-1 mutants were impaired in growth and development. These results indicate that LCB Δ4-desaturation is a prerequisite for the formation of the most abundant glycosylceramides in P. patens. However, loss of unsaturated LCBs does not affect plant viability, while blockage of glycosylceramide synthesis in gcs-1 plants causes severe plant growth and development defects.
Confirmation of ξ1 CMa’s ultra-slow rotation: magnetic polarity reversal and a dramatic change in magnetospheric UV emission lines
Authors: Erba C , Shultz M E , Petit V , Fullerton A W , Henrichs H F , Kochukhov O , Rivinius T , Wade G A
Published: May 2021

The magnetic β Cep pulsator ξ1 CMa has the longest rotational period of any known magnetic B-type star. It is also the only magnetic B-type star with magnetospheric emission that is known to be modulated by both rotation and pulsation. We report here the first unambiguous detection of a negative longitudinal magnetic field in ξ1 CMa (〈Bz〉 = −87 ± 2 G in 2019 and 〈Bz〉 = −207 ± 3 G in 2020), as well as the results of ongoing monitoring of the star’s H α variability. We examine evidence for deviation from a purely dipolar topology. We also report a new HST UV spectrum of ξ1 CMa obtained near magnetic null that is consistent with an equatorial view of the magnetosphere, as evidenced by its similarity to the UV spectrum of β Cep obtained near maximum emission. The new UV spectrum of ξ1 CMa provides additional evidence for the extremely long rotation period of this star via comparison to archival data.
Enhanced delivery of peptide-morpholino oligonucleotides with a small molecule to correct splicing defects in the lung
Authors: Dang Yan , van Heusden Catharina , Nickerson Veronica , Chung Felicity , Wang Yang , Quinney Nancy L , Gentzsch Martina , Randell Scott H , Moulton Hong M , Kole Ryszard , Ni Aiguo , Juliano Rudolph L , Kreda Silvia M
Published: May 2021

Pulmonary diseases offer many targets for oligonucleotide therapeutics. However, effective delivery of oligonucleotides to the lung is challenging. For example, splicing mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) affect a significant cohort of Cystic Fibrosis (CF) patients. These individuals could potentially benefit from treatment with splice switching oligonucleotides (SSOs) that can modulate splicing of CFTR and restore its activity. However, previous studies in cell culture used oligonucleotide transfection methods that cannot be safely translated in vivo. In this report, we demonstrate effective correction of a splicing mutation in the lung of a mouse model using SSOs. Moreover, we also demonstrate effective correction of a CFTR splicing mutation in a pre-clinical CF patient-derived cell model. We utilized a highly effective delivery strategy for oligonucleotides by combining peptide-morpholino (PPMO) SSOs with small molecules termed OECs. PPMOs distribute broadly into the lung and other tissues while OECs potentiate the effects of oligonucleotides by releasing them from endosomal entrapment. The combined PPMO plus OEC approach proved to be effective both in CF patient cells and in vivo in the mouse lung and thus may offer a path to the development of novel therapeutics for splicing mutations in CF and other lung diseases.
Structure of the mammalian adenine DNA glycosylase MUTYH: insights into the base excision repair pathway and cancer
Authors: Nakamura Teruya , Okabe Kohtaro , Hirayama Shogo , Chirifu Mami , Ikemizu Shinji , Morioka Hiroshi , Nakabeppu Yusaku , Yamagata Yuriko
Published: May 2021

Mammalian MutY homologue (MUTYH) is an adenine DNA glycosylase that excises adenine inserted opposite 8-oxoguanine (8-oxoG). The inherited variations in human MUTYH gene are known to cause MUTYH-associated polyposis (MAP), which is associated with colorectal cancer. MUTYH is involved in base excision repair (BER) with proliferating cell nuclear antigen (PCNA) in DNA replication, which is unique and critical for effective mutation-avoidance. It is also reported that MUTYH has a Zn-binding motif in a unique interdomain connector (IDC) region, which interacts with Rad9–Rad1–Hus1 complex (9–1–1) in DNA damage response, and with apurinic/apyrimidinic endonuclease 1 (APE1) in BER. However, the structural basis for the BER pathway by MUTYH and its interacting proteins is unclear. Here, we determined the crystal structures of complexes between mouse MUTYH and DNA, and between the C-terminal domain of mouse MUTYH and human PCNA. The structures elucidated the repair mechanism for the A:8-oxoG mispair including DNA replication-coupled repair process involving MUTYH and PCNA. The Zn-binding motif was revealed to comprise one histidine and three cysteine residues. The IDC, including the Zn-binding motif, is exposed on the MUTYH surface, suggesting its interaction modes with 9–1–1 and APE1, respectively. The structure of MUTYH explains how MAP mutations perturb MUTYH function.
A large-scale comparative study on peptide encodings for biomedical classification
Authors: Spänig Sebastian , Mohsen Siba , Hattab Georges , Hauschild Anne-Christin , Heider Dominik
Published: May 2021

Owing to the great variety of distinct peptide encodings, working on a biomedical classification task at hand is challenging. Researchers have to determine encodings capable to represent underlying patterns as numerical input for the subsequent machine learning. A general guideline is lacking in the literature, thus, we present here the first large-scale comprehensive study to investigate the performance of a wide range of encodings on multiple datasets from different biomedical domains. For the sake of completeness, we added additional sequence- and structure-based encodings. In particular, we collected 50 biomedical datasets and defined a fixed parameter space for 48 encoding groups, leading to a total of 397 700 encoded datasets. Our results demonstrate that none of the encodings are superior for all biomedical domains. Nevertheless, some encodings often outperform others, thus reducing the initial encoding selection substantially. Our work offers researchers to objectively compare novel encodings to the state of the art. Our findings pave the way for a more sophisticated encoding optimization, for example, as part of automated machine learning pipelines. The work presented here is implemented as a large-scale, end-to-end workflow designed for easy reproducibility and extensibility. All standardized datasets and results are available for download to comply with FAIR standards.
A map of the SARS-CoV-2 RNA structurome
Authors: Andrews Ryan J , O’Leary Collin A , Tompkins Van S , Peterson Jake M , Haniff Hafeez S , Williams Christopher , Disney Matthew D , Moss Walter N
Published: May 2021

SARS-CoV-2 has exploded throughout the human population. To facilitate efforts to gain insights into SARS-CoV-2 biology and to target the virus therapeutically, it is essential to have a roadmap of likely functional regions embedded in its RNA genome. In this report, we used a bioinformatics approach, ScanFold, to deduce the local RNA structural landscape of the SARS-CoV-2 genome with the highest likelihood of being functional. We recapitulate previously-known elements of RNA structure and provide a model for the folding of an essential frameshift signal. Our results find that SARS-CoV-2 is greatly enriched in unusually stable and likely evolutionarily ordered RNA structure, which provides a large reservoir of potential drug targets for RNA-binding small molecules. Results are enhanced via the re-analyses of publicly-available genome-wide biochemical structure probing datasets that are broadly in agreement with our models. Additionally, ScanFold was updated to incorporate experimental data as constraints in the analysis to facilitate comparisons between ScanFold and other RNA modelling approaches. Ultimately, ScanFold was able to identify eight highly structured/conserved motifs in SARS-CoV-2 that agree with experimental data, without explicitly using these data. All results are made available via a public database (the RNAStructuromeDB: https://structurome.bb.iastate.edu/sars-cov-2) and model comparisons are readily viewable at https://structurome.bb.iastate.edu/sars-cov-2-global-model-comparisons.
Assessing the functional relevance of splice isoforms
Authors: Pozo Fernando , Martinez-Gomez Laura , Walsh Thomas A , Rodriguez José Manuel , Di Domenico Tomas , Abascal Federico , Vazquez Jesús , Tress Michael L
Published: May 2021

Alternative splicing of messenger RNA can generate an array of mature transcripts, but it is not clear how many go on to produce functionally relevant protein isoforms. There is only limited evidence for alternative proteins in proteomics analyses and data from population genetic variation studies indicate that most alternative exons are evolving neutrally. Determining which transcripts produce biologically important isoforms is key to understanding isoform function and to interpreting the real impact of somatic mutations and germline variations. Here we have developed a method, TRIFID, to classify the functional importance of splice isoforms. TRIFID was trained on isoforms detected in large-scale proteomics analyses and distinguishes these biologically important splice isoforms with high confidence. Isoforms predicted as functionally important by the algorithm had measurable cross species conservation and significantly fewer broken functional domains. Additionally, exons that code for these functionally important protein isoforms are under purifying selection, while exons from low scoring transcripts largely appear to be evolving neutrally. TRIFID has been developed for the human genome, but it could in principle be applied to other well-annotated species. We believe that this method will generate valuable insights into the cellular importance of alternative splicing.
IgG Antibody Responses Are Preferential Compared With IgM for Use as Serological Markers for Detecting Recent Exposure to Plasmodium vivax Infection
Authors: Longley Rhea J , White Michael T , Brewster Jessica , Liu Zoe S J , Bourke Caitlin , Takashima Eizo , Harbers Matthias , Tham Wai-Hong , Healer Julie , Chitnis Chetan E , Monteiro Wuelton , Lacerda Marcus , Sattabongkot Jetsumon , Tsuboi Takafumi , Mueller Ivo
Published: May 2021

To achieve malaria elimination, new tools are required to explicitly target Plasmodium vivax. Recently, a novel panel of P. vivax proteins were identified and validated as serological markers for detecting recent exposure to P. vivax within the last 9 months. In order to improve the sensitivity and specificity of these markers, immunoglobulin M (IgM) in addition to immunoglobulin G (IgG) antibody responses were compared with a down-selected panel of 20 P. vivax proteins. IgM was tested using archival plasma samples from observational cohort studies conducted in malaria-endemic regions of Thailand and Brazil. IgM responses to these proteins generally had poorer classification performance than IgG.
Infra-Occipital Supra-Tentorial Approach for Resection of Low-Grade Tumor of the Left Lingual Gyrus: 2-Dimensional Operative Video
Authors: De Benedictis Alessandro , de Palma Luca , Herur-Raman Aalap , Pepi Chiara , Colafati Giovanna Stefania , Carboni Alessia , Randi Franco , Savioli Alessandra , Ricci Giuseppe , Mastronuzzi Angela , Carai Andrea , Specchio Nicola , Marras Carlo Efisio
Published: May 2021

Surgical treatment of lesions involving the postero-medial occipito-temporal region is challenging because of high risk of morbidity due to damage or excessive retraction of critical neuro-vascular structures, especially within the dominant hemisphere.
1-3

 Here, we describe the case of a 17-yr-old patient who underwent resection of an epileptogenic low-grade tumor located within the left-dominant lingual gyrus. Seizures were characterized, as a first symptom, by right-sided simple visual hallucination that pointed to the left pericalcarine region, corresponding to the lesion location. No signs of primary involvement of anterior temporo-mesial structures (hippocampus/amygdala) were found. As the anatomo-electroclinical correlation was concordant, direct tumor removal was indicated through an infra-occipital supratentorial approach.

 This route allowed direct access to the target through a safe extra-axial corridor, which limits intraparenchymal dissection until the tumor margin is identified and avoids critical vascular structures, such as the vein of Labbé.
4,5
An external cerebrospinal fluid (CSF) drainage was used to facilitate brain relaxation, minimizing brain and venous retraction and, consequently, reducing the risk of postoperative neurological complications, especially for vision. Postoperative magnetic resonance imaging (MRI) demonstrated no surgical complications. Pathological examination revealed a ganglioglioma. At 9-mo follow-up, the neurological examination was normal, antiepileptic therapy was stopped, and the patient was seizure-free.

 The video describes the main surgical steps, using both intraoperative videos and advanced 3-dimensional modeling of neuroimaging pictures.

 Informed consent was obtained for surgery and video recording.
Lymphoid stromal cells—more than just a highway to humoral immunity
Authors: Cinti Isabella , Denton Alice E
Published: May 2021

The generation of high-affinity long-lived antibody responses is dependent on the differentiation of plasma cells and memory B cells, which are themselves the product of the germinal centre (GC) response. The GC forms in secondary lymphoid organs in response to antigenic stimulation and is dependent on the coordinated interactions between many types of leucocytes. These leucocytes are brought together on an interconnected network of specialized lymphoid stromal cells, which provide physical and chemical guidance to immune cells that are essential for the GC response. In this review we will highlight recent advancements in lymphoid stromal cell immunobiology and their role in regulating the GC, and discuss the contribution of lymphoid stromal cells to age-associated immunosenescence.
The history and future of AI
Authors: Russell Stuart
Published: May 2021

The standard model for developing AI systems assumes a fixed, known objective that the AI system is required to optimize through its actions. Systems developed within the standard model have been increasingly successful. I briefly summarize the state of the art and its likely evolution over the next decade. Substantial breakthroughs leading to general-purpose AI are much harder to predict, but they will have an enormous impact on the global economy and on human roles therein. At the same time, I expect that the standard model will become increasingly untenable in real-world applications because of the difficulty of specifying objectives completely and correctly. I propose a new model for AI development in which the machine’s uncertainty about the true objective leads to qualitatively new modes of behaviour that are more robust, controllable, and deferential.
A time to act: Anti-racist paediatric research
Authors: Smile Sharon , Williams Alison
Published: May 2021

Research offers the potential for new treatments, programs and services, and underlies decisions about funding that can have profound implications for people’s lives. When racism in research is not addressed, children and their families will be unjustly impacted by systemic discrimination, exclusion, and inequity. With a growing acknowledgement that racism is a social determinant of health, and as COVID-19 reveals staggering racial disparities, we believe now is the time for intentional anti-racism initiatives throughout the research ecosystem to prevent further harms in patient care and the lives and futures of children. We aim to highlight this need for justice, and conclude with a series of practical recommendations, ranging from the collection and use of race-based data, to equity, diversity, and inclusion (EDI) education, to mentorship opportunities.
Back So Soon? A Community Hospital Creates New Ways to Prevent Readmission
Authors: Wrotny Cathy
Published: May 2021

Purpose/Objectives:

Readmission prevention is part of the hospital's strategic plan. Why? Reducing hospital readmissions decreases patient suffering. It also reduces the Centers for Medicare & Medicaid Services financial penalty. But how do you do it? The hospital received a 2-year grant/“investment” from the Massachusetts Health Policy Commission to develop and implement creative, innovative ways of reducing readmissions. The goal was to reduce the 30-day readmission rate for two groups by 20%—adult high utilizers (4 or more admissions within a 12-month period) and adult discharges to post-acute care (PAC) services (skilled nursing facilities and home care agencies).

Primary Practice Settings:

The primary practice settings for the initiative were the hospital, skilled nursing facilities, a short-term rehabilitation hospital, and the patients' homes. The patients were initially selected according to risk criteria determined by the hospital and then followed in the post-acute venue via telephone call and/or visit.

Findings/Conclusions:

Enrollment consisted of 2,860 patients. The readmission rate for adult high utilizers fell from 40.1% to 24.6% (a 39% reduction). The PAC readmissions for both skilled nursing facilities and home health agencies fell from 12.9% to 12.5%—a small decrease. However, the overall PAC readmission rate for the CHART (Community Hospital Acceleration, Revitalization, and Transformation) program is significantly lower than the state's—the rate for home health agencies is 17.2% and for skilled nursing facilities is 20.0%—making the effort to reduce the readmission rate all the more challenging. The significant reduction in hospital readmissions is attributed to the work of the Readmission Prevention Team, which met daily to discuss patients. Team members shared perceptions on patient education, medication management, communication, and end-of-life care. The team developed innovative practices and protocols, which were then applied to the patients' care.

Implications for Readmission Specialists Practice/Case Management:
Back So Soon? Part 2
Authors: Wrotny Cathy , Bradley Dona , Brulé Maurice
Published: May 2021

Purpose/Objectives:

Readmission prevention strategies are the focus of many hospitals, but despite these efforts, unplanned, all-payer hospital readmission rates are increasing. The purpose of this study was to use root cause analysis (RCA) to explore the main cause (medical, behavioral health, and/or social) for the unplanned 30-day readmissions that the Readmission Prevention Team followed up and then to use this data to change and/or refine discharge planning interventions.

Primary Practice Setting:

The primary practice setting was the 229-bed study hospital where subjects with 30-day unplanned readmissions who were followed up by the Readmission Prevention Team were admitted. The venues that subjects were readmitted from were noted as home without services, home with home care, skilled nursing facility (SNF), acute rehab, physician office, hospice/palliative care, and refused care.

Methodology and Sample:

Using a descriptive, correlational, qualitative design, demographic data (age, gender, days between discharge and readmission, and the venue from which the patient was readmitted) were collected from the RCA worksheets of each subject with an unplanned hospital readmission within 30 days.

Results:

Among the 150 subjects, the main cause for readmission was medical (92%), with 19 of the subjects (13%) demonstrating multiple root causes. Women were readmitted more frequently than men, and the prominent age range was the 70s and 80s. The two main readmission venues were home with home care (54.7%) and skilled nursing facilities (23.3%).

Implications for Case Management:

Medical was the chief cause of readmissions in this study, with many case management interventions noted in the literature to address these issues. Behavioral health and social issues were responsible for 13% of the readmissions. These issues are more complex, and hospitals should review the interventions that they have in place and develop others that are needed to decrease these types of readmissions.

Home with home care was the main venue of readmission, with return from a skilled nursing facility (SNF) being the second. Potential interventions to decrease these unplanned hospital readmissions might include developing a backup discharge plan (Option B) and developing improved communication avenues between the hospital emergency department and the SNF that might lead to the patient returning to the SNF versus being admitted.
Real-time SARS-CoV-2 diagnostic and variants tracking over multiple candidates using nanopore DNA sequencing
Authors: Stüder François , Petit Jean-Louis , Engelen Stefan , Mendoza-Parra Marco Antonio
Published: May 2021

Since December 2019, the emergence of a novel coronavirus responsible for a severe acute respiratory syndrome (SARS-CoV-2) is accountable for a major pandemic situation. As consequence, a major effort worldwide has been performed for the development of viral diagnostics strategies aiming at (i) reducing the diagnostics time, (ii) decrease the costs per assay, and (iii) providing population-scale solutions.

Beyond the diagnostics requirements, the description of the B.1.1.7 strain, originated in the south of England, as a highly transmissible variant has strongly accelerated the world-wide interest in tracking SARS-CoV-2 variants’ occurrence. Since then, other extremely infectious variants, were described and unsurprisingly further others are expected to be discovered, notably due to the long period of time on which the pandemic situation is lasting.

Interestingly, all currently described SARS-CoV-2 variants present systematically several mutations within the gene encoding the Spike protein, involved in host receptor recognition and entry into the cell. Hence, instead of sequencing the whole viral genome for variants’ tracking, our proposed strategy focuses on the SPIKE region, as a way to increase the number of candidate samples to screen at once; an essential aspect to accelerate SARS-CoV-2 diagnostics, but also improve variants’ emergence and progression surveillance.

Herein we present a proof of concept study, for performing both at once, population-scale SARS-CoV-2 diagnostics and variants’ tracking. This strategy relies on (i) the use of the portable and affordable MinION DNA sequencer; (ii) a DNA barcoding strategy and a SPIKE gene-centered variant’s tracking, for largely increasing the number of candidates per assay; and (iii) a real-time diagnostics and variant’s tracking monitoring thanks to our software RETIVAD.

As a whole, this strategy represents an optimal solution for addressing the current needs on SARS-CoV-2 progression surveillance, notably due to its affordable implementation, allowing its implantation even in remote places over the world.
Neuroprotective effect of vitamin B6 and vitamin B12 against vincristine- induced peripheral neuropathy: A randomized, double- blind, placebo controlled, multicenter trial
Authors: Jeenia Fatiha Tasmin , Sojib Ferdaush Ahmed , Rahman Md Sayedur , Ara Tasneem , Khan Rafiquzzaman , Tanin Md Jamal Uddin
Published: May 2021

Background

Vincristine leads to development of debilitating neuropathy in 40-45% patients with resultant compromised efficacy of chemotherapy, suboptimal treatment and worse prognostic outcome. Vitamin B6 and vitamin B12 improves non-oncological neuropathies. Therefore, this study investigated vitamin B6 and vitamin B12 to prevent vincristine- induced peripheral neuropathy (VIPN) by reducing incidence, absolute risk, relative risk, severity as well as delaying the onset.

Methods

Patients with ALL undergoing induction phase were randomly assigned into intervention or placebo arm in a double- blind manner. Vitamin B6 (25 mg Pyridoxine) two tablets were given three times daily for 5 weeks. Vitamin B12 (500 μg/ml Methylcobalamin) was administered intravenously on day 1, 3 and 5 of every week for 5 weeks during induction period. Placebo arm received oral and intravenous placebo for same duration. Patients were evaluated on the outset of every week by FACT/GOG-NTX questionnaire. Severity was assessed per NCI-CTCAE grading scale.

Results

102 patients were enrolled. Among them 81 completed the study, where 42 received vitamin B6 and B12 and 39 received placebo. There was significant difference in incidence of neuropathy between arms (26.19% intervention arm, 56.41% placebo; P-0.01). Relative risk of neuropathy was significantly (RR-0.46) lower in intervention arm. Besides, absolute risk reduction (ARR) was 30% and relative risk reduction (RRR) was 54%. NNT was 3.33. Significant trend was observed in difference of severity of VIPN between groups (P-0.03). No significant difference observed in between arms for time to onset of neuropathy.

Conclusion

Vitamin B6 and vitamin B12 significantly reduced the incidence, relative risk and severity of VIPN. NNT was encouraging too. Henceforth, the status of vitamin B6 and vitamin B12 as neuroprotective agent against VIPN can be recommended as a promising one. Clinicaltrials.gov ID: NCT02923388
Mechanistic model calibration and the dynamics of the COVID-19 epidemic in the UK (the past, the present and the future)
Authors: Conn Harry , Taylor Robyn , Willis Mark J. , Wright Allen , Bramfitt Victoria
Published: May 2021

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We augment the well-known susceptible – infected – recovered – deceased (SIRD) epidemiological model to include vaccination dynamics, implemented as a piecewise continuous simulation. We calibrate this model to reported case data in the UK at a national level,

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Our modelling approach decouples the inherent characteristics of the infection from the degree of human interaction (as defined by the effective reproduction number,Re). This allows us to detect and infer a change in the characteristic of the infection, for example the emergence of the Kent variant,

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We find that that the infection rate constant (k) increases by around 89% as a result of the B.1.1.7 (Kent) COVID-19 variant in England,

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Through retrospective analysis and modelling of early epidemic case data (between March 2020 and May 2020) we estimate that ∼1.2M COVID-19 infections were unreported in the early phase of the epidemic in the UK. We also obtain an estimate of the basic reproduction number as,R0= 3.23,

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We use our model to assess the UK Government’s roadmap for easing the third national lockdown as a result of the current vaccination programme. To do this we use our estimated model parameters and a future forecast of the daily vaccination rates of the next few months,

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Our modelling predicts an increased number of daily cases as NPIs are lifted in May and June 2021,

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We quantify this increase in terms of the vaccine rollout rate and in particular the percentage vaccine uptake rate of eligible individuals, and show that a reduced take up of vaccination by eligible adults may lead to a significant increase in new infections.