bluuebunny/crossref_metadata_2025 huggingface dataset:
The Frequency and Perceived Effectiveness of Pain Self-Management Strategies Used by Individuals With Migraine
Authors: CHANG Hao-Yuan , YANG Chih-Chao , JENSEN Mark P. , LAI Yeur-Hur
Published: April 2021

Background

Migraine is ranked among the most important causes of disability worldwide. Some effective migraine treatments have been identified. However, little is known regarding the treatment strategies used by patients with migraine to manage pain or their efficacy.

Purpose

This study was designed to (a) investigate the pain management strategies used by migraineurs and their perceived effectiveness and (b) evaluate the association between the number of strategies used and their overall perceived effectiveness.

Methods

A cross-sectional design with consecutive sampling was used in a medical center in Taiwan. Individuals with migraine (N = 174) completed self-administered questionnaires and in-depth interviews to assess the frequency and perceived effectiveness of a variety of pain management strategies.

Results

Most participants reported using prescription medications (56%) and over-the-counter medications (51%), which were rated as having good efficacy rates of 78% and 81%, respectively. Traditional Chinese medicine (17%) and folk remedies (13%) were used less frequently and rated as relatively less effective at 65% and 48%, respectively. About half (47%) reported using more than one pain management strategy. Significantly more of those who reported using multiple pain management strategies reported at least “some effect” than those who reported using one strategy only (73% vs. 27%, p = .001).

Conclusions

Prescription medications showed good usage rate and good perceived efficacy. However, about half of the participants used multiple pain management strategies, supporting the need for further research to evaluate the efficacy of combination treatments and to identify those combinations that may have the most additive and/or synergistic effects. Furthermore, the findings indicate that continued use of medications for migraine management is appropriate for many individuals because of the relatively high rates of perceived efficacy for this strategy found in this study.
Family Members' Knowledge and Attitude Toward Life-Sustaining Treatment Decisions for Patients in the Intensive Care Unit
Authors: Kim Sunjung , Tak Sunghee H.
Published: April 2021

The decision to withhold or withdraw life-sustaining treatment (LST) lies sometimes in the hands of intensive care unit patients' families. Since 2018, family members of dying patients in South Korea have had the legal right to make decisions for the patients. This study aimed to examine knowledge and attitude toward LST among the family members of patients under intensive care since the foundation of the new legislation. Their perceptions of the roles of nurses were also explored. In this cross-sectional study, 89 participants completed survey questionnaires on demographic characteristics, relationship to patient, reason for admission, length of stay, awareness of the new legislation, knowledge and attitude toward LST, and perception of the role of nurses. The results indicated that knowledge was significantly associated with attitude and was, in fact, the only predictor of attitude toward LST (P = .021). Explaining the disease and prognosis in detail and relieving patients of their physical pain were the roles of nurses most valued by family members. The findings suggest that it is crucial for nurses to support family members and provide information about critical changes and medical options for collaborative decision making according to the patients' wishes during the dying process.
The Relationship Between Dental Agenesis and Maxillary Hypoplasia in Patients With Cleft Lip and Palate
Authors: Janes Lindsay E. , Bazina Mohamed , Morcos Sherif S. , Ukaigwe Angelica , Valiathan Manish , Jacobson Ronald , Gosain Arun K.
Published: April 2021

Both dental agenesis and maxillary growth restriction are well-recognized sequelae in patients with unilateral cleft lip and palate, but their etiology remains controversial. The aim of this study was to evaluate the relationship between hypodontia and maxillary volume. A retrospective review of patients age 6 to 9 with Veau III (unilateral) cleft palate who underwent Cone Beam Computer Tomography in preparation for alveolar bone grafting at 2 major Children's Hospitals between 2010 and 2016 was conducted and serial panoramic radiographs were reviewed. Thirty-eight patients were identified that met inclusion criteria and had adequate imaging. Group 1 (“poor growers”) consisted of the bottom 50% of Sella-Nasion-A point minus Sella-Nasion-B point (ANB) angles and Group 2 (“good growers”) consisted of the top 50% of ANB angles. Group 1 had a significantly higher mean number of missing teeth (1.58 ± 0.28 missing teeth) compared to Group 2 (0.74 ± 0.23 missing teeth), and significantly lower maxillary volume (12.88 ± 0.61 cm3 versus 15.24 ± 0.88 cm3, respectively). The severity of maxillary hypoplasia in cleft patients increases with increased dental agenesis. These data indicate that intrinsic factors play a significant role in maxillary growth restriction in cleft patients, independent of the sequelae of surgical intervention.
Endoscopic Surgical Treatment of Maxillary Sinus Organized Hematoma
Authors: Jeong Se Hyun , Lee Dong Hoon , Lim Sang Chul
Published: April 2021

Objective:

The purpose of this study was to analyze the clinical characteristics and treatment outcomes of patients who underwent endoscopic surgery for a maxillary sinus organized hematoma during a 15-year period in our hospital.

Methods:

The authors analyzed 25 patients who underwent endoscopic surgery for a maxillary sinus organized hematoma from January 2004 to December 2019.

Results:

Twenty-five patients with a maxillary sinus organized hematoma underwent endoscopic surgical treatment and complete removal of the maxillary sinus organized hematoma was achieved in all cases. The main symptoms were nasal bleeding in 14 patients, followed by a nasal obstruction in nine, and facial swelling in 2. Of the 25 patients, 13 underwent endoscopic medial maxillectomy and 12 underwent endoscopic sinus surgery. There were no major surgical complications or recurrences.

Conclusion:

The authors demonstrated that endoscopic surgery is a safe and reliable treatment method for a maxillary sinus organized hematoma.
Fascicular Turnover Flap: An Approach for Facial Nerve Reconstruction
Authors: Ferry Andrew M. , Manfro Gabriel , Dias Fernando Luiz , Teixeira Gilberto Vaz , Cernea Claudio Roberto , Abu-Ghname Amjed , Maricevich Marco
Published: April 2021

Facial nerve injuries are a common complication associated with parotidectomy. These functionally debilitating injuries are conventionally treated with nonvascularized nerve grafting; however, this reconstructive modality produces moderate donor site morbidity and has limited efficacy for repairing large defects. In addition, nonvascularized nerve grafts are highly susceptible to radiotherapy and require a well-vascularized wound bed to produce adequate therapeutic results. The fascicular turnover flap, described by Koshima et al, utilizes a single fascicle to bridge two nerve endings that are in series with no donor site morbidity. Although studies have demonstrated this technique's efficacy, there is a paucity of data regarding its use in patients undergoing facial nerve reconstruction. Herein, we describe our early clinical experience using the fascicular turnover flap to reconstruct branches of the facial nerve in patients undergoing extensive parotidectomy. Our patients underwent successful reconstruction of the nerve defects produced by parotidectomy using the fascicular turnover flap. Despite postoperative radiotherapy, both patients demonstrated complete functional recovery at six months postoperatively. Although formal head-to-head studies are needed to compare the outcomes of this technique versus conventional nerve grafting for facial nerve reconstruction, our preliminary experiences suggest that the fascicular turnover flap is a viable modality of reconstruction with great potential.
Comparison of Magnetic Resonance Imaging and Computed Tomography in the Evaluation of the Olfactory Cleft and Ethmoidal Cells
Authors: Hemmi Tomotaka , Nomura Kazuhiro , Suzuki Jun , Kobayashi Yuta , Kakuta Risako , Sugawara Mitsuru , Katori Yukio
Published: April 2021

No study has examined whether magnetic resonance imaging (MRI) alone can be used for evaluating olfactory cleft and ethmoidal sinus in patients with olfactory disorders. Therefore, we analyzed the discrepancies between computed tomography (CT) and MRI in the imaging of the olfactory cleft and ethmoidal sinus. Patients who underwent CT and MRI within 30 days were evaluated. Age, sex, diagnosis, presence of bronchial asthma (BA), peripheral blood eosinophil percentage, and CT and MRI findings were retrospectively reviewed, and the sinuses were assessed on a scale of 0 to 3. Overall, 146 patients with 292 sinuses were enrolled. The ethmoid sinus score and the olfactory cleft score had 77.1% and 72.6% image similarity in CT and MRI. Sex and BA status were not associated with olfactory cleft score discrepancies (sex: P = 0.52, BA: P = 0.41). Magnetic resonance imaging scores tended to be rated higher than the CT scores as age increased, although this difference was not statistically significant (P = 0.09). The higher the peripheral blood eosinophil percentage, the more the magnitude by which the CT score tended to exceed the MRI score; however, this finding was also not statistically significant (P = 0.11). Magnetic resonance imaging scans should be limited to the evaluation of intracranial regions. Scans of olfactory cleft and ethmoid cells are not accurate for the assessment of olfactory dysfunction.
Prognosis and Risk Factors of Sepsis Patients in Chinese ICUs: A Retrospective Analysis of a Cohort Database
Authors: Qu Zeyu , Zhu Yibing , Wang Meiping , Li Wen , Zhu Bo , Jiang Li , Xi Xiuming
Published: April 2021

Background:

Sepsis-3 proposed a new definition of septic shock that excluded patients without hyperlactacidemia. The data from China might help to elucidate the prognosis of this special patient group.

Objective:

To study the clinical prognosis and factors affecting patients with sepsis based on data from Chinese intensive care units (ICUs).

Methods:

We conducted a retrospective, multicentre observational study in a larger Chinese cohort from January 1, 2014 to August 31, 2015. The patients were divided into four groups according to the presence or absence of hypotension/vasopressor delivery and hyperlactacidemia after fluid resuscitation. Descriptive statistics for the clinical characteristics were presented. The differences between groups were assessed. A survival curve was then plotted using the Kaplan-Meier method. Finally, to better understand the risk factors for the 28-day hospital mortality rates, Cox regression analysis was performed.

Results:

In total, 1,194 patients with sepsis were included: 282 with hypotension and hyperlactacidemia, 250 with hypotension but without hyperlactacidemia, 161 with hyperlactacidemia but without hypotension, and 501 without hypotension and hyperlactacidemia. The 28-day mortality rates of the four groups were 48.2%, 43.2%, 26.1%, and 24.8%, respectively. Age, the Acute Physiology And Chronic Health Evaluation (APACHE) II score, hyperlactacidemia, hypotension, intra-abdominal infection, and cancer increased the risk of the 28-day mortality, while soft tissue infection and coming from the operating room were associated with a decreased risk of mortality.

Conclusions:

Patients with hypotension but without hyperlactacidemia in the ICU also show a high 28-day mortality, and some clinical factors may affect their prognosis and must be treated carefully in the future.
Targets for migraine treatment: beyond calcitonin gene-related peptide
Authors: Moreno-Ajona David , Villar-Martínez María Dolores , Goadsby Peter J.
Published: April 2021

Purpose of review

Despite the development of several medications for the acute and preventive treatment of migraine, there are still many patients in whom lack of efficacy, tolerability, interactions or contraindications make other options necessary. CGRP-based drugs have opened the door to a new era of migraine-targeted treatments. Beyond CGRP, there are other promising targets covered here.

Recent findings

For the acute treatment of migraine, 5-HT1Freceptor agonists, ditans, are now available. Unlike triptans, 5-HT1B/1Dreceptor agonists, cardiovascular disease is not a contraindication for the use of ditans. The first study on a monoclonal antibody targeting PAC1 receptor was negative, although this may not be the end for the pituitary adenylate cyclase-activating polypeptide (PACAP) pathway as a target.

Following positive phase-III clinical trials, lasmiditan is the first ditan to be FDA-approved. PACAP has experimental evidence suggesting a role in migraine pathophysiology. As for CGRP, the presence of PACAP in key migraine structures along with positive provocative tests for both PACAP-38 and PACAP-27 indicate this pathway may still be a pharmacological target. Glutamate-based targets have long been considered in migraine. Two clinical trials with memantine, an NMDA-R antagonist, for the preventive treatment of migraine have now been published. The hypothalamus has also been implicated in migraine pathophysiology: the potential role of orexins in migraine is discussed. Acid-sensing ion channels, as well as amylin-blocking drugs, may also become migraine treatments in the future: more research is warranted.
Highly effective disease-modifying treatment as initial MS therapy
Authors: Schmierer Klaus , Sørensen Per S. , Baker David
Published: April 2021

Purpose of review

Using highly effective (HE) compounds right from the beginning of disease-modifying immunotherapy (DMT) in people with multiple sclerosis (pwMS) has gained popularity among clinicians and pwMS alike. We discuss the most recent evidence supporting this approach, and whether any of the associated risks should stop us adopting it as a default strategy.

Recent findings

With the addition of injectable ofatumumab, and the two oral sphingosine one phosphate modulators siponimod and ozanimod, ten HE DMTs are now available for pwMS, though variation in licensing status and cost may limit their use in some healthcare environments. Real World evidence based on large MS registry data suggests the superiority of early HE DMT over a slow treatment escalation approach; delaying HE DMT leads to more rapid and often irreversible disability accrual. Mechanistically, B-cell depletion, particularly memory B-cell suppression, is a common denominator closely associated with DMT efficacy.

The concept that HE DMTs are necessarily associated with a high risk of adverse effects, is no longer supported by the evidence. The rather predictable and manageable risk profile of most HE DMTs should lower the threshold for clinicians to discuss such treatment with pwMS as a first line approach.
A Randomized, Double-Blind, Sham-Controlled Study of Transcranial Direct Current Stimulation as an Augmentation Intervention for the Attenuation of Motor Deficits in Patients With Stroke
Authors: Pinto Ekta Franscina , Gupta Anupam , Kulkarni Girish Baburao , Andrade Chittaranjan
Published: April 2021

Introduction

Most studies of transcranial direct current stimulation (tDCS) for motor deficits in patients with stroke administered few sessions of tDCS and with low current amplitude.

Methods

During 2015 to 2019, we randomized 60 inpatients with ischemic/hemorrhagic stroke and motor deficits to true or sham tDCS. Transcranial direct current stimulation was administered at 2- to 3-mA current strength, twice daily, 6 days a week, for 2 weeks; anode and cathode were placed over ipsilesional and contralesional motor cortices, respectively. All patients received individualized motor and cognitive rehabilitation. Motor outcomes were assessed 1 day before and 1 day after the tDCS course using the Fugl-Meyer Assessment, the Jebson-Taylor Hand Function Test, and the Barthel index (all coprimary outcomes). Mood and cognition were also assessed. Motor outcomes were compared between groups using age, baseline scores, and latency to treatment as covariates. The study was prospectively registered (CTRI/2017/01/007733).

Results

The mean age of the patients was 46.9 years. The sample was 73.3% male. Six patients did not complete the study. The covariates were significantly related to motor outcomes. Although all patients showed motor improvements, after adjusting for covariates, tDCS was not superior to sham treatment on any motor, mood, or cognitive outcome. Laterality of hemispheric lesion influenced spatial but not motor outcomes with tDCS. One true tDCS patient developed blistering under the anode and was withdrawn from the study; 3 more reported transient itching during sessions.

Conclusions

An intensive course of tDCS, as delivered in this study, does not improve motor, mood, and cognitive outcomes in ischemic/hemorrhagic stroke in patients undergoing individualized rehabilitation. The study provides important leads for directions for future research.
The infectivity of progeny adenovirus in the presence of neutralizing antibody
Authors: Hirai Takamasa , Sato Anna , Koizumi Naoya , Kurioka Yoh , Suzuki Yui , Kano Junpei , Yamakawa Makie , Nomura Tetsuya , Fujii Makiko , Sakurai Fuminori , Mizuguchi Hiroyuki , Watanabe Yoshiteru , Utoguchi Naoki
Published: April 2021

Human adenoviruses (Ads), common pathogens that cause upper respiratory and gastrointestinal infections, are blocked by neutralizing antibodies (nAbs). However, Ads are not fully eliminated even in hosts with nAbs. In this study, we assessed the infectivity of progeny Ad serotype 5 (Ad5) in the presence of nAb. The infectivity of Ad5 was evaluated according to the expression of the Ad genome and reporter gene. Infection by wild-type Ad5 and Ad5 vector continued to increase until 3 days after infection even in the presence of nAb. We established an assay for determining the infection levels of progeny Ad5 using a sorting system with magnetic beads and observed little difference in progeny Ad5 counts in the presence and absence of nAb 1 day after infection. Moreover, progeny Ad5 in the presence of nAb more effectively infected coxsackievirus and adenovirus receptor (CAR)-positive cells than CAR-negative cells. We investigated the function of fiber proteins, which are the binding partners of CAR, during secondary infection, observing that fibre proteins spread from infected cells to adjacent cells in a CAR-dependent manner. In conclusion, this study revealed that progeny Ad5 could infect cells even in the presence of nAb, differing from the common features of the Ad5 infection cycle. Our findings may be useful for developing new therapeutic agents against Ad infection.
Measuring Salivary Cortisol in Wild Carnivores
Authors: Montgomery Tracy M. , Greenberg Julia R. , Gunson Jessica L. , John Kecil , Laubach Zachary M. , Nonnamaker Emily , Person Erin S. , Rogers Heidi , Ronis Emily , Smale Laura , Steinfield Katherine , Strong Robyn , Holekamp Kay E. , Beehner Jacinta C.
Published: April 2021

Salivary hormone analyses provide a useful alternative to fecal and urinary hormone analyses in non-invasive studies of behavioral endocrinology. Here, we use saliva to assess cortisol levels in a wild population of spotted hyenas (Crocuta crocuta), a gregarious carnivore living in complex social groups. We first describe a novel, non-invasive method of collecting saliva from juvenile hyenas and validate a salivary cortisol assay for use in this species. We then analyze over 260 saliva samples collected from nearly 70 juveniles to investigate the relationships between cortisol and temporal and social variables in these animals. We obtain evidence of a bimodal daily rhythm with salivary cortisol concentrations dropping around dawn and dusk, times at which cub activity levels are changing substantially. We also find that dominant littermates have lower cortisol than either subordinate littermates or singletons, but that cortisol does not vary with age, sex, or maternal social rank. Finally, we examine how social behaviors such as aggression or play affect salivary cortisol concentrations. We find that inflicting aggression on others was associated with lower cortisol concentrations. We hope that the detailed description of our methods provides wildlife researchers with the tools to measure salivary cortisol in other wild carnivores.

HIGHLIGHTS

We validated methods for collecting and analyzing saliva from wild carnivores.

We documented a bimodal daily rhythm in juvenile spotted hyena salivary cortisol.

Cortisol varied among juvenile hyenas based on litter size and intra-litter rank.

Inflicting aggression on others was associated with lower cortisol concentrations.
Lower promoter activity of theST8SIA2gene has been favored in evolving human collective brains
Authors: Hayakawa Toshiyuki , Terahara Masahiro , Fujito Naoko T. , Matsunaga Takumi , Teshima Kosuke , Hane Masaya , Kitajima Ken , Sato Chihiro , Takahata Naoyuki , Satta Yoko
Published: April 2021

ST8SIA2 is the main factor regulating expression of the phenotype involved in schizophrenia. Lowered promoter activity of theST8SIA2gene is considered to be protective against schizophrenia by conferring tolerance to psychosocial stress. Here, we examined the promoter type composition of anatomically modern humans (AMHs) and archaic humans (AHs; Neanderthals and Denisovans), and compared the promoter activity at the population level (population promoter activity; PPA) between them. In AMHs, the TCT-type, showing the second lowest promoter activity, was most prevalent in the ancestral population of non-Africans. However, the detection of only the CGT-type from AH samples and recombination tracts in AH sequences showed that the CGT- and TGT-types, exhibiting the two highest promoter activities, were common in AH populations. Furthermore, interspecies gene flow occurred into AMHs from AHs and into Denisovans from Neanderthals, influencing promoter-type compositions independently in both AMHs and AHs. The difference of promoter-type composition makes PPA unique in each population. East and Southeast Asian populations show the lowest PPA. This results from the selective increase of the CGC-type, showing the lowest promoter activity, in these populations. Every non-African population shows significantly lower PPA than African populations, resulting from the TCT-type having the highest prevalence in the ancestral population of non-Africans. In addition, PPA reduction is also found among subpopulations within Africa via a slight increase of the TCT-type. These findings indicate a trend toward lower PPA in the spread of AMHs, interpreted as a continuous adaptation to psychosocial stress arising in migration. This trend is considered as genetic tuning for the evolution of collective brains. The inferred promoter-type composition of AHs differed markedly from that of AMHs, resulting in higher PPA in AHs than in AMHs. This suggests that the trend toward lower PPA is a unique feature in AMH spread.
Targeting cancer glycosylation repolarizes tumor-associated macrophages allowing effective immune checkpoint blockade
Authors: Stanczak Michal A. , Mantuano Natalia Rodrigues , Kirchhammer Nicole , Sanin David E. , Wang Jinyu , Trefny Marcel P. , Monaco Gianni , Gray Melissa A. , Petrone Adam , Kashyap Abhishek S. , Glatz Katharina , Kasenda Benjamin , Normington Karl , Broderick James , Peng Li , Pearce Oliver M.T. , Pearce Erika L. , Bertozzi Carolyn R. , Zippelius Alfred , Läubli Heinz
Published: April 2021

Immune checkpoint blockade (ICB) has significantly improved the prognosis of cancer patients, but the majority experience limited benefit, evidencing the need for new therapeutic approaches. Upregulation of sialic acid-containing glycans, termed hypersialylation, is a common feature of cancer-associated glycosylation, driving disease progression and immune escape via the engagement of Siglec-receptors on tumor-infiltrating immune cells. Here, we show that tumor sialylation correlates with distinct immune states and reduced survival in human cancers. The targeted removal of Siglec-ligands in the tumor microenvironment, using an antibody-sialidase conjugate, enhances anti-tumor immunity and halts tumor progression in several mouse tumor models. Using single-cell RNA sequencing, we reveal desialylation mechanistically to repolarize tumor-associated macrophages (TAMs) and identify Siglec-E on TAMs as the main receptor for hypersialylation. Finally, we show genetic and therapeutic desialylation, as well as loss of Siglec-E, to synergize with ICB. Thus, therapeutic desialylation represents a novel immunotherapeutic approach, shaping macrophage phenotypes and augmenting the adaptive anti-tumor immune response.
An evidence-based 3D reconstruction of Asteroxylon mackiei the most complex plant preserved from the Rhynie chert
Authors: Hetherington Alexander J. , Bridson Siobhán L. , Jones Anna Lee , Hass Hagen , Kerp Hans , Dolan Liam
Published: April 2021

The 407-million-year-old Rhynie chert preserves the earliest terrestrial ecosystem and informs our understanding of early life on land. However, our knowledge of the 3D structure, and development of these plants is still rudimentary. Here we used digital 3D reconstruction techniques to produce the first complete reconstruction of the lycopsid Asteroxylon mackiei, the most complex plant in the Rhynie chert. The reconstruction reveals the organisation of the three distinct axes types – leafy shoot axes, root-bearing axes and rooting axes – in the body plan. Combining this reconstruction with developmental data from fossilised meristems, we demonstrate that the A. mackiei rooting axis – a transitional lycophyte organ between the rootless ancestral state and true roots – developed from root-bearing axes by anisotomous dichotomy. Our discovery demonstrates how this unique organ developed, and highlights the value of evidence-based reconstructions for understanding the development and evolution of the first complex plants on Earth.
Analysis of Conformational Exchange Processes using Methyl-TROSY-Based Hahn Echo Measurements of Quadruple-Quantum Relaxation
Authors: Waudby Christopher A. , Christodoulou John
Published: April 2021

Transverse nuclear spin relaxation can be a sensitive probe of chemical exchange on timescales on the order of microseconds to milliseconds. Here we present an experiment for the simultaneous measurement of the relaxation rates of two four-spin transitions in selectively protonated methyl groups within perdeuterated biomacromolecules, alongside control experiments for measurement of1H and13C chemical shift anisotropies. We show that analysis of the static magnetic field dependence of zero-, double- and quadruple-quantum Hahn echo relaxation rates provides a robust indication of chemical exchange and determines the signed relative magnitudes of proton and carbon chemical shift differences between ground and excited states. The analysis can be combined with CPMG relaxation dispersion measurements to provide improved precision, particularly in the determination of1H chemical shift differences.
Cell Surface Multimeric Assemblies Regulate Canonical and Noncanonical EphA2 Receptor Tyrosine Kinase Signaling
Authors: Shi Xiaojun , Lingerak Ryan , Herting Cameron J. , Ge Yifan , Kim Soyeon , Toth Paul , Cuizon Carmelle , Zheng Ji , Chao Luke , Sossey-Alaoui Khalid , Buck Matthias , Singh Salendra , Varadan Vinay , Himanen Juha , Hambardzumyan Dolores , Nikolov Dimitar , Smith Adam W. , Wang Bingcheng
Published: April 2021

The EphA2 receptor tyrosine kinase mediates ligand-induced canonical signaling associated with tumor suppression and ligand-independent noncanonical signaling implicated in tumor progression. Using time-resolved fluorescence spectroscopy in live cells, we find that unliganded EphA2 receptors pre-assemble into multimers, which is mediated by two symmetric and one asymmetric interfaces in the ectodomain. Upon ligand binding, EphA2 receptors are further assemble into large clusters that also requires the three interfaces. Functionally, disrupting either the symmetric or asymmetric contacts individually blocks the autorecycling of the EphA2 apo receptor. However, only symmetric contact disruption promotes noncanonical signaling and inhibits ligand-induced catalytic activation and endocytosis, which are associated with increased cell migrationin vitroand reduced survival in a syngeneic murine glioblastoma model. Our results reveal the pivotal role of EphA2 assembly in dictating canonical vs. noncanonical signaling, and identify the precise molecular interfaces that mediate the formation of the EphA2 signaling clusters.
Genetic Basis for Lentil Adaptation to Summer Cropping in Northern Temperate Environments
Authors: Haile Teketel A. , Stonehouse Robert , Weller James L. , Bett Kirstin E.
Published: April 2021

The continued success of lentil (Lens culinarisMedik.) genetic improvement relies on the availability of broad genetic diversity and new alleles need to be identified and incorporated into the cultivated gene pool. Availability of robust and predictive markers greatly enhances the precise transfer of genomic regions from unadapted germplasm. Quantitative trait loci (QTLs) for key phenological traits in lentil were located using a recombinant inbreed line (RIL) population derived from a cross between an Ethiopian landrace (ILL 1704) and a northern temperate cultivar (CDC Robin). Field experiments were conducted at Sutherland research farm in Saskatoon and at Rosthern, Saskatchewan, Canada during 2018 and 2019. A linkage map was constructed using 21,634 SNPs located on seven linkage groups (LGs) which correspond to the seven haploid chromosomes of lentil. Eight QTL were identified for six phenological traits. Flowering related QTL were identified at two regions on LG6.FLOWERING LOCUS T(FT) genes were annotated within the flowering time QTL interval based on the lentil reference genome. Similarly, a major QTL for post-flowering developmental processes was located on LG5 with several senescence-associated genes annotated within the QTL interval. The flowering time QTL was validated in a different genetic background indicating the potential use of the identified markers for marker-assisted selection to precisely transfer genomic regions from exotic germplasm into elite crop cultivars without disrupting adaptation.

Core Ideas

Stable QTL were located for key phenological traits in lentil that lead to regional adaptation.

FTgenes are candidates for controlling flowering time in lentil grown in temperate environments.

A major locus controlling post-flowering developmental processes was located on lentil LG5 with several senescence-associated genes annotated within the QTL interval.

Markers identified in this study can be useful for marker-assisted selection to precisely transfer genomic regions from exotic germplasm into elite lentil cultivars without disrupting adaptation.
Vacuole phase-partitioning boosts mitochondria activity and cell lifespan through an inter-organelle lipid pipeline
Authors: Seo AY , Sarkleti F , Budin I , Chang C , King C , Kohlwein S-D , Sengupta P , Lippincott-Schwartz J
Published: April 2021

Functional linkage between mitochondria and lysosomes is crucial for survival under starvation and lifespan extension. Despite such co-dependency, the supportive pathways connecting mitochondria and lysosomes remain unclear. Here, we identify an inter-organelle lipid trafficking pathway linking yeast vacuole and mitochondria that results in increased mitochondria growth and respiratory activity under glucose starvation. The pathway depends on vacuolar phase-separated, lipid domains, which provide zones for: activation of the vacuolar proton pump; lipid droplet (LD) docking and internalization; and, lipid transfer from vacuole-to-ER-to-mitochondria. Partitioned vacuolar domains form through a specialized type of macro-autophagy, triggered only under acute glucose starvation, that delivers sterol-rich, endosomal-derived lipids to the vacuole. To balance this lipid influx, the vacuole reroutes lipids back to the ER to support both LD biogenesis and mitochondria growth and activity. Energy produced by enhanced mitochondrial activity then feeds back to support the inter-organelle lipid trafficking pathways to ensure survival under nutrient stress.
Direct and indirect pathway neurons in ventrolateral striatum differentially regulate licking movement and nigral responses
Authors: Chen Zhaorong , Zhang Zhi-Yu , Zhang Wen , Xie Taorong , Li Yaping , Xu Xiao-Hong , Yao Haishan
Published: April 2021

Drinking behavior in rodents is characterized by stereotyped, rhythmic licking movement, which is regulated by the basal ganglia. It is unclear how direct and indirect pathways control the lick bout and individual spout contact. We find that inactivating D1 and D2 receptors-expressing medium spiny neurons (MSNs) in the ventrolateral striatum (VLS) oppositely alters the number of licks in a bout. D1- and D2-MSNs exhibit different patterns of lick sequence-related activity and different phases of oscillation time-locked to the lick cycle. On timescale of a lick cycle, transient inactivation of D1-MSNs during tongue protrusion reduces spout contact probability, whereas transiently inactivating D2-MSNs has no effect. On timescale of a lick bout, inactivation of D1-MSNs (D2-MSNs) causes rate increase (decrease) in a subset of basal ganglia output neurons that decrease firing during licking. Our results reveal the distinct roles of D1- and D2-MSNs in regulating licking at both coarse and fine timescales.
Gauge your phage: Benchmarking of bacteriophage identification tools in metagenomic sequencing data
Authors: Ho Siu Fung Stanley , Wheeler Nicole , Millard Andrew D. , van Schaik Willem
Published: April 2021

Background

The prediction of bacteriophage sequences in metagenomic datasets has become a topic of considerable interest, leading to the development of many novel bioinformatic tools. A comparative analysis of ten state-of-the-art phage identification tools was performed to inform their usage in microbiome research.

Methods

Artificial contigs generated from complete RefSeq genomes representing phages, plasmids, and chromosomes, and a previously sequenced mock community containing four phage species, were used to evaluate the precision, recall and F1-scores of the tools. We also generated a dataset of randomly shuffled sequences to quantify false positive calls. In addition, a set of previously simulated viromes was used to assess diversity bias in each tool’s output.

Results

VirSorter2 achieved the highest F1 score (0.92) in the RefSeq artificial contigs dataset, with several other tools also performing well. Kraken2 had the highest F1 score (0.86) in the mock community benchmark by a large margin (0.3 higher than DeepVirFinder in second place), mainly due to its high precision (0.96). Generally, k-mer based tools performed better than reference similarity tools and gene-based methods. Several tools, most notably PPR Meta, called a high number of false positives in the randomly shuffled sequences. When analysing the diversity of the genomes that each tool predicted from a virome set, most tools produced a viral genome set that had similar alpha and beta diversity patterns to the original population, with Seeker being a notable exception.

Conclusions

This study provides key metrics used to assess performance of phage detection tools, offers a framework for further comparison of additional viral discovery tools, and discusses optimal strategies for using these tools. We highlight that the choice of tool for identification of phages in metagenomic datasets, as well as their parameters, can bias the results and provide pointers for different use case scenarios. We have also made our benchmarking dataset available for download in order to facilitate future comparisons of phage identification tools.
Ahead of Maturation: Enhanced Speech Envelope Training Boosts Rise Time Discrimination in Pre-Readers at Cognitive Risk for Dyslexia
Authors: Van Herck Shauni , Bempt Femke Vanden , Economou Maria , Vanderauwera Jolijn , Glatz Toivo , Dieudonné Benjamin , Vandermosten Maaike , Ghesquière Pol , Wouters Jan
Published: April 2021

Dyslexia has frequently been related to atypical auditory temporal processing and speech perception. Results of studies emphasizing speech onset cues and reinforcing the temporal structure of the speech envelope, i.e. envelope enhancement, demonstrated reduced speech perception deficits in individuals with dyslexia. The use of this strategy as an auditory intervention might thus reduce some of the deficits related to dyslexia. Importantly, interventions are most effective when they are provided during kindergarten and first grade. Hence, we provided a tablet-based 12-week preventive auditory and phonics-based intervention to pre-readers at cognitive risk for dyslexia and investigated the effect on auditory temporal processing with a rise time discrimination task. Ninety-one pre-readers at cognitive risk for dyslexia (aged 5-6) were assigned to two groups receiving a phonics-based intervention and playing a story listening game either with (n= 31) or without (n= 31) envelope enhancement or a third group playing control games and listening to non-enhanced stories (n= 29). Rise time discrimination was measured directly before, directly after and one year after the intervention. While the groups listening to non-enhanced stories mainly improved after the intervention during first grade, the group listening to enhanced stories improved during the intervention in kindergarten and subsequently remained stable during first grade. Hence, an envelope enhancement intervention improves auditory processing skills important for the development of phonological skills. This occurred before the onset of reading instruction, preceding the maturational improvement of these skills, hence giving at risk children a head start when learning to read.

Research highlights

The first investigation of speech envelope enhancement as a potential preventive intervention strategy in pre-readers at cognitive risk for dyslexia

Speech envelope enhancement increases the rise time sensitivity of children at cognitive risk for dyslexia

Rise time discrimination can be enhanced before formal reading instruction, a crucial period in development
Human Fronto-Striatal Connectivity is Organized into Discrete Functional Subnetworks
Authors: Gordon Evan M. , Laumann Timothy O. , Marek Scott , Newbold Dillan J. , Hampton Jacqueline M. , Seider Nicole A. , Montez David F. , Nielsen Ashley M. , Van Andrew N. , Zheng Annie , Miller Ryland , Siegel Joshua S. , Kay Benjamin P. , Snyder Abraham Z. , Greene Deanna J. , Schlaggar Bradley L. , Petersen Steven E. , Nelson Steven M. , Dosenbach Nico U.F.
Published: April 2021

The striatum is interconnected with the cerebral cortex via multiple recurrent loops that play a major role in many neuropsychiatric conditions. Primate cortico-striatal connections can be precisely mapped using invasive tract-tracing. However, noninvasive human research has not mapped these connections with anatomical precision, limited by the practice of averaging neuroimaging data across individuals. Here we utilized highly-sampled resting-state functional connectivity MRI for individually-specific precision functional mapping of cortico-striatal connections. We identified ten discrete, individual-specific subnetworks linking cortex—predominately frontal cortex—to striatum. These subnetworks included previously unknown striatal connections to the human language network. The discrete subnetworks formed a stepped rostral-caudal gradient progressing from nucleus accumbens to posterior putamen; this organization was strongest for projections from medial frontal cortex. The stepped gradient organization fit patterns of fronto-striatal connections better than a smooth, continuous gradient. Thus, precision subnetworks identify detailed, individual-specific stepped gradients of cortico-striatal connectivity that include human-specific language networks.
Revealing the threat of emerging SARS-CoV-2 mutations to antibody therapies
Authors: Chen Jiahui , Gao Kaifu , Wang Rui , Wei Guo-Wei
Published: April 2021

The ongoing massive vaccination and the development of effective intervention offer the long-awaited hope to end the global rage of the COVID-19 pandemic. However, the rapidly growing SARS-CoV-2 variants might compromise existing vaccines and monoclonal antibody (mAb) therapies. Although there are valuable experimental studies about the potential threats from emerging variants, the results are limited to a handful of mutations and Eli Lilly and Regeneron mAbs. The potential threats from frequently occurring mutations on the SARS-CoV-2 spike (S) protein receptor-binding domain (RBD) to many mAbs in clinical trials are largely unknown. We fill the gap by developing a topology-based deep learning strategy that is validated with tens of thousands of experimental data points. We analyze 261,348 genome isolates from patients to identify 514 non-degenerate RBD mutations and investigate their impacts on 16 mAbs in clinical trials. Our findings, which are highly consistent with existing experimental results about variants from the UK, South Africa, Brazil, US-California, and Mexico shed light on potential threats of 95 high-frequency mutations to mAbs not only from Eli Lilly and Regeneron but also from Celltrion and Rockefeller University that are in clinical trials. We unveil, for the first time, that high-frequency mutations R346K/S, N439K, G446V, L455F, V483F/A, E484Q/V/A/G/D, F486L, F490L/V/S, Q493L, and S494P/L might compromise some of mAbs in clinical trials. Our study gives rise to a general perspective about how mutations will affect current vaccines.
Cryptocurrency bubble risk and the FOMC announcements during COVID-19 black swan event
Authors: Jarboui Anis , Mnif Emna
Published: April 2021

Purpose

After the COVID-19 outbreak, the Federal Reserve has undertaken several monetary policies to alleviate the pandemic consequences on the markets. This paper aims to evaluate the effects of the Federal Reserve monetary policy on the cryptocurrency dynamics during the COVID19 pandemic.

Design/methodology/approach

We examine the response and feedback effects via an event study methodology. For this purpose, abnormal returns (AR) and cumulative abnormal returns (CARs) around the first FOMC (Federal Open Market Committee) announcement related to the COVID-19 pandemic for the top five cryptocurrencies are explored. We, further investigate the effect of the eight FOMC statement announcements during the COVID19 pandemic on these cryptocurrencies (Bitcoin, Ethereum, Tether, Litecoin, and Ripple). In the above-mentioned crypto-currency markets, we investigate the presence of bubbles by using the PSY test. We then examine the concordance of the dates of these bubbles with the dates of the FOMC announcements.

Findings

The empirical results show that the first FOMC event has a negative significant effect after 4 days of the announcement date for all studied cryptocurrencies except Tether. The results also indicate that cumulative abnormal returns are significant during the event windows of (−3,8), (−3,9), and (−3,10). Besides, we find that Bitcoin, Ethereum and, Litecoin lived short bubbles lasting for a few days. However, Ripple and Tether markets present no bubbles and no explosive periods.

Research limitations/implications

This paper presents trained proof that FOMC announcements have a positive effect on volatility's predictive capacity. This work therefore promotes the study of the data quality of volatility in future research as well.

Practical implications

The justified effect of the FOMC announcements on cryptocurrency as a speculative asset has practical implications for investors in building their trading strategies in anticipation of the next FOMC announcement. Therefore, this study implies that the FOMC announcements contain very relevant information for investors in the cryptocurrency market. This research may not only encourage a better understanding of the evolution of the expectations of policymakers, but also facilitate a better understanding of how these expectations are developed.

Originality/value

The COVID-19 pandemic has disturbed the stability of financial markets, inciting the Fed to take some monetary regulations. To the best of our knowledge, this study is the first one that analyses the response of five major cryptocurrencies to FOMC announcements during COVID 19 pandemic and associates these dates with bubble occurrences.
Safari tourism and its role in sustainable poverty eradication in East Africa: the case of Kenya
Authors: Maingi Shem Wambugu
Published: April 2021

Purpose

Globally, poverty has been a persistent problem despite decades of unprecedented growth. The purpose of this paper is to deliberate on a sustainable livelihoods and poverty eradication approach in an African context.

Design/methodology/approach

The paper aims to bridge the gaps in poverty eradication strategies in East Africa by examining recent literature on livelihoods approaches and poverty eradication approaches.

Findings

Safari tourism is one way of connecting poor communities in Kenya to the tourism industry. The development of community conservancies in Kenya presents yet more opportunities for communities to be integrated with the sector. The Africanization of the tourism sector in Kenya is a priority, as communities embrace tourism and poverty eradication measures.

Practical implications

There is a need for the Safari tourism sector to integrate the local community’s indigenous knowledge systems, community social capital and the community’s natural capital with tourism product development and diversification.

Originality/value

The paper draws on applied research and technical analysis of the unique opportunities for enhancing sustainable poverty eradication through the tourism sector in East Africa and, more particularly, a Kenyan context.