bluuebunny/crossref_metadata_2025 huggingface dataset:
A Critical Evaluation of “The Ear that Hears Badly” in the Ebers Papyrus
Authors: Mudry Albert , Young John Riddington
Published: June 2021

Objective:

The Ebers papyrus (1,550 BC) is one of the most complete medical papyri of Ancient Egypt. It contains a few paragraphs about otology, about both treatments of the external ear and ideas concerning the ears and deafness. Over the years, many scholarly interpretations of these paragraphs have been made by learned Egyptologists and academic historians of otology. They do not always agree and have often been critical of each other. This historical review compares and contrasts all the main published academic translations of the Ebers papyrus by looking at the original document and their interpretations.

Methodology:

Historical research, based on the various translations of the Ebers papyrus.

Results:

Eight complete translations of the whole Ebers manuscript have been analyzed. Four of these contain transliteration of the hieroglyphics. The hieroglyph associated with the ear is a pictogram of a cow's ear. It has two possible interpretations. It can mean the ear itself but it can also be used to denote either deafness or hearing.

Conclusion:

Insights into the early Egyptians perception of the ear may be obtained, but study of primary references shows that there is scant evidence of knowledge of anatomical details in the Ebers papyrus.
Inflammatory Pseudotumor of the Temporal Bone Leading to Atypical Superior Semicircular Canal Dehiscence Syndrome: A Novel Case Report
Authors: Smith Blaine D. , Cunningham Calhoun D.
Published: June 2021

Objective:

Inflammatory pseudotumor of the temporal bone is a benign idiopathic inflammatory process that is rarely encountered in clinical practice. We describe a novel case of a patient who developed superior semicircular canal dehiscence syndrome in the setting of active inflammatory pseudotumor of the temporal bone.

Patient:

One female patient found to have inflammatory pseudotumor of the temporal bone. After treatment with mastoidectomy and steroids, she subsequently developed superior semicircular canal dehiscence syndrome.

Intervention(s):

The patient initially underwent myringotomy and pressure equalization tube placement for a unilateral effusion. Imaging with computed tomography and magnetic resonance imaging revealed a lytic mastoid mass. A complete mastoidectomy was diagnostic for inflammatory pseudotumor and the patient was treated with adjuvant long-term corticosteroids. After this procedure, she was discovered to have new development of symptomatic superior semicircular canal dehiscence syndrome. She eventually underwent a trans-mastoid repair of her superior semicircular canal dehiscence.

Main Outcome Measure(s):

The patient's clinical course is described with emphasis on the development of superior semicircular canal dehiscence syndrome in the setting of active inflammatory pseudotumor of the temporal bone.

Results:

The patient's radiographic and clinical history were found to be consistent with inflammatory pseudotumor of the temporal bone. She underwent a therapeutic mastoidectomy with long-term post-operative corticosteroids. During her post-operative course, she developed symptoms of vertigo, hearing loss, and autophony. She was subsequently diagnosed with superior semicircular canal dehiscence and treated with a trans-mastoid repair of the dehiscence. Her symptoms satisfactorily resolved after this surgery.

Conclusions:

Inflammatory pseudotumor of the temporal bone is a rare benign inflammatory process. We present what is to our knowledge the first description of superior semicircular canal dehiscence syndrome developing in the setting of inflammatory pseudotumor.
Nurse Burnout Syndrome and Work Environment Impact Patient Safety Grade
Authors: Montgomery Aoyjai P. , Patrician Patricia A. , Azuero Andres
Published: June 2021

Background:

Burnout impacts nurses' health as well as brain structures and functions including cognitive function, which could lead to work performance and patient safety issues. Yet, few organization-level factors related to patient safety have been identified.

Purpose:

This study examined nurse-reported patient safety grade and its relationship to both burnout and the nursing work environment.

Methods:

A cross-sectional electronic survey was conducted among nurses (N = 928) in acute care Alabama hospitals.

Results:

In multilevel ordinal mixed-effects models with nurses nested within hospitals, all burnout dimensions of the Copenhagen Burnout Inventory (OR for +1 SD ranging 0.63-0.78; P < .05) and work environment (OR for +1 SD ranging 4.35-4.89; P < .001) were related to the outcome of patient safety grade after controlling for nurse characteristics.

Conclusions:

Results indicate that health care organizations may reduce negative patient safety ratings by reducing nurse burnout and improving the work environment at the organization level.
Preparing Adipogenic Hydrogel with Neo-Mechanical Isolated Adipose-Derived Extracellular Vesicles for Adipose Tissue Engineering
Authors: Nie Jia-ying , Zhu Yuan-zheng , Wang Jiang-wen , Hu Xuan , Wang Zhao-hui , Wu Shu , Yi Yang-yan
Published: June 2021

Background:

Subcutaneous transplantation of decellularized adipose tissue was capable of recellularization during soft tissue repair. However, further improvements are required to promote angiogenesis and adipogenesis. Here, the authors proposed a neo-mechanical protocol to isolate adipose tissue–derived extracellular vesicles (ATEVs) through lipoaspirate as a mediator for both angiogenesis and adipogenesis, and prepared ATEV-rich decellularized adipose tissue hydrogel for adipose tissue engineering.

Methods:

Adipose liquid extract and lipid-devoid adipose tissue were extracted through homogenization and repeated freeze and thaw cycles. ATEVs were isolated from adipose liquid extract by ultracentrifugation. Decellularized adipose tissue hydrogel was prepared by optimized decellularization of lipid-devoid adipose tissue. The optimum dose of ATEVs for angiogenesis and adipogenesis was estimated by co-culturing with vascular endothelial cells and 3T3-L1 cells, then mixed with the hydrogel. ATEV-enriched hydrogel was injected subcutaneously into the back of severe combined immunodeficiency mice, and then subjected to supplementary injection of ATEVs on postoperative day 14. ATEV-free decellularized adipose tissue hydrogel was injected as control. The newly formed tissue samples were harvested at postoperative weeks 2, 4, and 8 and subjected to volume measurement, hematoxylin and eosin staining, and immunofluorescence (CD31 and perilipin) staining.

Results:

The optimum dose of ATEVs for promoting angiogenesis and adipogenesis was 50 μg/ml. The newly formed tissue mediated by ATEV-enriched hydrogel had increased volume well as improved angiogenesis and adipogenesis at postoperative week 4 and 8.

Conclusion:

ATEV-enriched adipogenic hydrogel promotes enhanced angiogenesis and adipogenesis and could serve as a promising biomaterial for adipose tissue engineering.
Barriers and Facilitators to Engagement in Rehabilitation Among Stroke Survivors
Authors: Forgea Mary C. , Lyons Amy G. , Lorenz Rebecca A.
Published: June 2021

Background

Approximately 795,000 Americans experience a new or recurrent stroke every year, and it remains one of the leading causes of disability worldwide. Patient engagement in rehabilitation and physical activity has been associated with improvements in functional outcomes during inpatient rehabilitation. There is limited knowledge of the barriers and facilitators to patients’ engagement in stroke rehabilitation.

Methods

An integrative review with a systematic approach was conducted to explore the current available literature on barriers and facilitators to patient engagement in stroke inpatient rehabilitation.

Results

Twenty-five studies were included in the final review. Four major themes described the identified barriers and facilitators: (1) stroke impact, (2) self-efficacy, (3) therapeutic relationship, and (4) motivating factors. Individualized patient-centered goal setting was a commonly studied intervention found to successfully increase engagement.

Conclusion

Engagement in stroke rehabilitation is associated with improved patient outcomes. Using the identified themes from this review, nurses can develop focused interventions aimed at reducing barriers and increasing stroke patient engagement.
Validity and Reliability of the Home Enteral Nutrition Caregiver Task Checklist
Authors: Sezer Ceren Rana Elcin , Talas Melek Serpil , Goksuluk Dincer
Published: June 2021

The aim of this study was to establish validity and reliability of “the Home Enteral Nutrition Caregiver Task Checklist” for the Turkish population. The study sample consisted of 70 caregivers of patients with percutaneous endoscopic gastrostomy (PEG) tubes discharged from a hospital. The language and content validity and reliability stages were completed, respectively. The content validity index was 0.98, Cronbach's α 0.75, and Pearson correlation test r = 0.86 for the checklist. This checklist is a reliable and valid tool for caregivers of patients with a PEG. Using this checklist in the care of patients with a PEG can help identify caregivers' training needs, the challenges they may have once home, and allow for more thorough and precise education to be provided prior to discharge.
Real-time Alerting System for COVID-19 Using Wearable Data
Authors: Alavi Arash , Bogu Gireesh K , Wang Meng , Rangan Ekanath Srihari , Brooks Andrew W , Wang Qiwen , Higgs Emily , Celli Alessandra , Mishra Tejaswini , Metwally Ahmed A. , Cha Kexin , Knowles Peter , Alavi Amir A , Bhasin Rajat , Panchamukhi Shrinivas , Celis Diego , Aditya Tagore , Honkala Alexander , Rolnik Benjamin , Hunting Erika , Dagan-Rosenfeld Orit , Chauhan Arshdeep , Li Jessi W , Li Xiao , Bahmani Amir , Snyder Michael P
Published: June 2021

Early detection of infectious disease is crucial for reducing transmission and facilitating early intervention. We built a real-time smartwatch-based alerting system for the detection of aberrant physiological and activity signals (e.g. resting heart rate, steps) associated with early infection onset at the individual level. Upon applying this system to a cohort of 3,246 participants, we found that alerts were generated for pre-symptomatic and asymptomatic COVID-19 infections in 78% of cases, and pre-symptomatic signals were observed a median of three days prior to symptom onset. Furthermore, by examining over 100,000 survey annotations, we found that other respiratory infections as well as events not associated with COVID-19 (e.g. stress, alcohol consumption, travel) could trigger alerts, albeit at a lower mean period (1.9 days) than those observed in the COVID-19 cases (4.3 days). Thus this system has potential both for advanced warning of COVID-19 as well as a general system for measuring health via detection of physiological shifts from personal baselines. The system is open-source and scalable to millions of users, offering a personal health monitoring system that can operate in real time on a global scale.
The relative strength and timing of innate immune and CD8 T-cell responses underlie the heterogeneous outcomes of SARS-CoV-2 infection
Authors: Chatterjee Budhaditya , Sandhu Harshbir Singh , Dixit Narendra M.
Published: June 2021

SARS-CoV-2 infection results in highly heterogeneous outcomes, from cure without symptoms to acute respiratory distress and death. While immunological correlates of disease severity have been identified, how they act together to determine the outcomes is unknown. Here, using a new mathematical model of within-host SARS-CoV-2 infection, we analyze diverse clinical datasets and predict that a subtle interplay between innate and CD8 T-cell responses underlies disease heterogeneity. Our model considers essential features of these immune arms and immunopathology from cytokines and effector cells. Model predictions provided excellent fits to patient data and, by varying the strength and timing of the immune arms, quantitatively recapitulated viral load changes in mild, moderate, and severe disease, and death. Additionally, they explained several confounding observations, including viral recrudescence after symptom loss, prolonged viral positivity before cure, and mortality despite declining viral loads. Together, a robust conceptual understanding of COVID-19 outcomes emerges, bearing implications for interventions.

Teaser

Modeling explains how a subtle interplay between innate immune and CD8 T-cell responses determines the severity of COVID-19.
Endonuclease-based genotyping of the RBM, a first-line method for the surveillance of emergence or evolution of SARS-CoV-2 Variants
Authors: Lopez Eva , Barthélémy Margot , Baronti Cécile , Masse Shirley , Falchi Alessandra , Durbesson Fabien , Vincentelli Renaud , de Lamballerie Xavier , Charrel Rémi , Coutard Bruno
Published: June 2021

Since the beginning of the Covid-19 pandemics, variants have emerged. Whereas most of them have no to limited selective advantage, some display increased transmissibility and/or resistance to immune response. To date, most of the mutations involved in the functional adaptation are found in the Receptor Binding Module (RBM), close to the interface with the human receptor ACE2. In this study, we thus developed and validated a fast and simple molecular assay allowing the detection and partial identification of the mutations in the RBM coding sequence. After the amplification of the region of interest, the amplicon is heat-denatured and hybridized with an amplicon of reference. The presence of a mutation in the heteroduplex can be cleaved by a mismatch-specific endonuclease and the cleavage pattern is analysed by capillary electrophoresis. The approach was first validated on viral RNA purified different SARS-CoV-2 variants produced in the lab before being implemented for clinical samples. The results highlighted the performance of the assay for the detection of mutations in the RBM from clinical samples. The procedure can be easily set up for high throughput identification of the presence of mutations and serve as a first-line screening to select the samples for full genome sequencing.
Seroprevalence of anti–SARS-CoV-2 antibodies in women attending antenatal care in eastern Ethiopia
Authors: Assefa Nega , Demissie Lemma , Teklemariam Zelalem , Oundo Joseph , Madrid Lola , Kebede Addisu , Dessie Yadeta , Scott J. Anthony G.
Published: June 2021

Information on the cumulative incidence of SARS-CoV-2 in East Africa is scarce. We conducted serosurveillance of anti–SARS-CoV-2 antibodies among pregnant women attending their first antenatal care visit in three health facilities in eastern Ethiopia.

We collected data using questionnaire and a blood sample from 3,312 pregnant women between April 1, 2020 and March 31, 2021 at health facilities in Haramaya, Aweday and Harar. We selected 1,447 blood samples at random and assayed these for anti-SARS-CoV-2 antibodies at Hararghe Health Research laboratory using WANTAI® SARS-CoV-2 Rapid Test for total immunoglobulin. Temporal trends in seroprevalence were analysed with a χ2 test for trend and multivariable binomial regression.

Among 1,447 sera tested, 83 were positive for anti–SARS-CoV-2 antibodies giving a crude seroprevalence of 5.7% (95% CI 4.6%, 7.0%). Of 160 samples tested in April-May, 2020, none was seropositive; the first seropositive sample was identified in June and seroprevalence rose steadily thereafter (χ2 test for trend, p=0.003) reaching a peak of 11.8% in February, 2021. In the multivariable model, seroprevalence was approximately 3% higher in first-trimester mothers compared to later presentations, and rose by 0.75% (95% CI 0.31%, 1.20%) per month of calendar time.

This clinical convenience sample illustrates the dynamic of the SARS-CoV-2 epidemic in young adults in eastern Ethiopia; infection was rare before June 2020 but it spread in a linear fashion thereafter, rather than following intermittent waves, and reached 10% by the beginning of 2021. After one year of surveillance, most pregnant mothers remained susceptible.
Public health relevant consequences of the COVID-19 pandemic on malaria in sub-Saharan Africa: A scoping review
Authors: Heuschen Anna-Katharina , Lu Guangyu , Razum Oliver , Abdul-Mumin Alhassan , Sankoh Osman , Seidlein Lorenz von , D’Alessandro Umberto , Müller Olaf
Published: June 2021

Background

The COVID-19 pandemic has resulted in unprecedented challenges to health systems worldwide, including the control of non-COVID-19 diseases. Malaria cases and deaths may increase due to the direct and indirect effects of the pandemic in malaria endemic countries, particularly in sub-Saharan Africa (SSA).

Objectives

This scoping review aims to summarize information on public health relevant effects of the COVID-19 pandemic on the malaria situation in SSA.

Methods

Review of publications and manuscripts on preprint servers, in peer-reviewed journals and in grey literature documents from December 1, 2019, to June 9, 2021. A structured search was conducted on different databases using predefined eligibility criteria for the selection of articles.

Results

A total of 51 papers have been included in the analysis. Modeling papers have predicted a significant increase in malaria cases and malaria deaths in SSA due to the effects of the COVID-19 pandemic. Many papers provided potential explanations for expected COVID-19 effects on the malaria burden; these ranged from relevant diagnostical and clinical aspects, to reduced access to health care services, impaired availability of curative and preventive commodities and medications, and effects on malaria prevention campaigns. Compared to previous years, fewer country reports provided data on the actual number of malaria cases and deaths in 2020, with mixed results. While highly endemic countries reported evidence of decreased malaria cases in health facilities, low endemic countries reported overall higher numbers of malaria cases and deaths in 2020.

Conclusions

The findings from this review provide evidence for a significant but diverse impact of the COVID-19 pandemic on malaria in SSA. There is the need to further investigate the public health consequences of the COVID-19 pandemic on the malaria burden.
Development of an index to assess Covid-19 hospital care installed capacity in the 450 Brazilian Health Regions
Authors: Pereira Claudia C. A. , Soares Fernando , Frio Gustavo , Machado Carla , Alves Layana , Herkrath Fernando , Lima Rodrigo , Barreto Ivana , Silva Everton , Andrade Anny , Santos Leonor
Published: June 2021

Objective: We assessed the Brazilian health system's ability to respond to the challenges imposed by the Covid-19 pandemic considering hospital capacity in the 450 Health Regions of the country in 2020. Hospital capacity referred to the availability of hospital beds, equipment, and human resources.
Methods: Data came from National Register of Health Facilities on the availability of Covid-19 resources in inpatient facilities from January to December,2020. Assessed resources were health professionals, hospital beds, and medical equipment. A synthetic indicator, Installed Capacity Index (ICI) was calculated using Principal Component Analysis.
Results: There was an increase in all selected indicators between January and December 2020. We observed differences between the Northeast, North regions, and the other regions of the country. Most Health Regions presented low ICI. The ICI increased especially in regions with considerably high baseline capacity in January 2020. The Northeast and North had a higher concentration of low ICI regions.
Conclusion: The information here provided may be used by health authorities, providers, and managers in planning and adjusting for future Covid-19 care and in dimensioning the adequate supply of hospital beds, health care professionals, and devices in Health Regions to reduce associated morbidity and mortality.
3D structure and in situ arrangements of CatSper channel in the sperm flagellum
Authors: Zhao Yanhe , Wang Huafeng , Wiesehoefer Caroline , Shah Naman B. , Reetz Evan , Hwang Jae Yeon , Huang Xiaofang , Lishko Polina V. , Davies Karen M. , Wennemuth Gunther , Nicastro Daniela , Chung Jean-Ju
Published: June 2021

The sperm calcium channel CatSper plays a central role in successful fertilization as a primary Ca2+ gateway into the sperm flagellum. However, CatSper’s complex subunit composition has impeded its reconstitution in vitro and structural elucidation. Here, we applied cryo-electron tomography to visualize the macromolecular organization of the native CatSper channel complex in intact mammalian sperm, as well as identified three additional CatSper-associated proteins. The repeating CatSper units form long zigzag-rows in four nanodomains along the flagella. In both mouse and human sperm, each CatSper repeat consists of a tetrameric pore complex. Murine CatSper contains an additional outwardly directed wing-structure connected to the tetrameric channel. The majority of the extracellular domains form a canopy above each pore-forming channel that interconnects to a zigzag-shaped roof. The intracellular domains link two neighboring channel complexes to a diagonal array. The loss of this intracellular link in Efcab9-/- sperm distorts the longitudinally aligned zigzag pattern and compromises flagellar movement. This work offers unique insights into the mechanisms underlying the assembly and transport of the CatSper complex to generate the nanodomains and provides a long-sought structural basis for understanding CatSper function in the regulation of sperm motility.
A tripartite cytolytic toxin formed by Vibrio cholerae proteins with flagellum-facilitated secretion
Authors: Nadeem Aftab , Nagampalli Raghavendra , Toh Eric , Alam Athar , Myint Si Lhyum , Heidler Thomas V. , Dongre Mitesh , Zlatkov Nikola , Pace Hudson , Bano Fouzia , Sjöstedt Anders , Bally Marta , Uhlin Bernt Eric , Wai Sun Nyunt , Persson Karina
Published: June 2021

The protein MakA was discovered as a motility-associated secreted toxin from Vibrio cholerae, Here, we show that MakA is part of a gene cluster encoding four additional proteins: MakB, MakC, MakD and MakE. The MakA, MakB and MakE proteins were readily detected in culture supernatants of wild type V. cholerae whereas secretion was very much reduced from a flagellum deficient mutant. Crystal structures of MakA, MakB and MakE revealed structural relationship to a superfamily of bacterial pore-forming proteins. Cloning and expression of MakA/B/E in Escherichia coli resulted in toxicity of the bacteria towards Caenorhabditis elegans used as a predatory organism model. None of these Mak proteins alone or in pairwise combinations were cytolytic but an equimolar mixture of MakA, MakB and MakE acted as a tripartite cytolytic toxin in vitro causing lysis of erythrocytes and cytotoxicity on cultured human colon carcinoma cells. Formation of oligomeric complexes on liposomes was observed by electron microscopy. Oligomer interaction with membranes was initiated by MakA membrane binding followed by MakB and MakE joining in formation of a pore structure. A predicted membrane insertion domain of MakA was shown by site-directed mutagenesis to be essential for toxicity towards C. elegans. Bioinformatic analyses revealed that the makCDBAE gene cluster is present as a novel genomic island in the vast majority of sequenced genomes of V. cholerae and the fish pathogen V. anguillarum. We suggest that the hitherto unrecognized cytolytic MakA/B/E toxin can contribute to Vibrionaceae fitness and virulence potential in different host environments and organisms.

Significance Statement

Vibrio cholerae, responsible for outbreaks and pandemics of cholera disease, is a highly motile organism by virtue of a single flagellum. We describe that the flagellum facilitates the secretion of three V. cholerae proteins encoded by a hitherto unrecognized novel genomic island. The proteins MakA/B/E can form a tripartite cytolytic toxin that lyses erythrocytes and is cytotoxic to cultured human cells. A structural basis for the Mak protein cytolytic activity was obtained by X-ray crystallography. Flagellum-facilitated secretion, remarkably ensuring spatially co-ordinated delivery of Mak proteins, revealed a new role for the V. cholerae flagellum considered of particular significance for the bacterial environmental persistence. Our findings will pave the way for the development of new diagnostics and therapeutic strategies against pathogenic Vibrionaceae.
Determinants of Murine Skin Microbiota Composition in Homeostasis and Wound Healing
Authors: Galbraith Jack , Legrand Julien M. D. , Muller Nicholas , Baz Betoul , Togher Katie , Matigian Nicholas , Kang Seungha , Young Sylvia , Mortlock Sally , Roy Edwige , Morahan Grant , Walker Graeme , Morrison Mark , Khosrotehrani Kiarash
Published: June 2021

Animal microbiota have complex interactions with hosts and environment that determines its composition. Yet the ability of hosts to determine their microbiota composition is less well studied. In this study, to investigate the role host genetics in determining skin microbiota, we used 30 different mouse strains from the recombinant inbred panel, the Collaborative Cross. Murine skin microbiota composition was strongly dependent on murine strain with > 50% of the variation explained by murine strain. In particular, a quantitative trait locus on chromosome 4 associates both with Staphylococcus abundance and principal-component multi-trait analyses. Additionally, excisional wound associated changes in microbiota composition were not uniform across mouse strains and were host-specific, the genetic background accounting for about 40% of the variation in microbiota. Genetic background also had the highest effect on the healing speed of wounds accounting for over 50% of the variation while mouse age and microbiota composition change accounted only for 20% and 5% of the healing speed despite reaching statistical significance. In conclusion, host genetics has a significant impact on the skin microbiota composition during both homeostasis and wound healing. These findings have long reaching implications in our understanding of associations between microbiota dysbiosis and disease.
Population inter-connectivity over the past 120,000 years explains distribution and diversity of Central African hunter-gatherers
Authors: Padilla-Iglesias Cecilia , Atmore Lane M. , Olivero Jesús , Lupo Karen , Manica Andrea , Isaza Epifanía Arango , Vinicius Lucio , Migliano Andrea Bamberg
Published: June 2021

The evolutionary history of African hunter-gatherers holds key insights into modern human diversity. Here we combine ethnographic and genetic data on Central African hunter-gatherers (CAHG) to show that their current distribution and density is explained by ecology rather than by a displacement to marginal habitats due to recent farming expansions, as commonly assumed. We also predict hunter-gatherer presence across Central Africa over the past 120,000 years using paleoclimatic reconstructions, which were statistically validated by dated archaeological sites. Finally, we show that genomic estimates of separation times between CAHG groups match our ecological estimates of periods favouring population splits, and that recoveries of connectivity would have facilitated subsequent gene-flow. Our results reveal that CAHG stem from a deep history of partially connected populations. This form of sociality allowed the coexistence of relatively large effective population sizes and local differentiation, with important implications for the evolution of genetic and cultural diversity in Homo sapiens.
Reliable in silico ranking of engineered therapeutic TCR binding affinities with MMPB/GBSA
Authors: Crean Rory M. , Pudney Christopher R. , Cole David K. , van der Kamp Marc W.
Published: June 2021

Accurate and efficient in silico ranking of protein-protein binding affinities is useful for protein design with applications in biological therapeutics. One popular approach to rank binding affinities is to apply the molecular mechanics Poisson Boltzmann/generalized Born surface area (MMPB/GBSA) method to molecular dynamics trajectories. Here, we identify protocols that enable the reliable evaluation of T-cell receptor (TCR) variants binding to their target, peptide-human leukocyte antigens (pHLAs). We suggest different protocols for variant sets with few (≤4) or many mutations, with entropy corrections important for the latter. We demonstrate how potential outliers could be identified in advance and that just 5-10 replicas of short (4 ns) MD simulations may be sufficient for reproducible and accurate ranking of TCR variants. The protocols developed here can be applied towards in silico screening during the optimization of therapeutic TCRs, potentially reducing both the cost and time taken for biologic development.
Adaptation of Drosophila larva foraging in response to changes in food distribution
Authors: Wosniack Marina E. , Hu Nan , Gjorgjieva Julijana , Berni Jimena
Published: June 2021

When foraging, animals combine internal cues and sensory input from their environment to guide sequences of behavioral actions. Drosophila larva executes crawls, turns, and pauses to explore the substrate and find food sources. This exploration has to be flexible in the face of changes in the quality of food so that larvae feed in patches with favorable food and look for another source when the current location does not fulfill their nutritional needs. But which behavioral elements adapt, and what triggers those changes remain elusive. Using experiments and modeling, we investigate the foraging behavior of larvae in homogeneous environments with different food types and in environments where the food sources are patchy. Our work indicates that the speed of larval crawling and frequency of pauses is modulated by the food quality. Interestingly, we found that the genetic dimorphism in the foraging gene influences the exploratory behavior only when larvae crawl on yeast patches. While in a homogeneous substrate larvae maintain a turning bias in a specific orientation, in a patchy substrate larvae orient themselves towards the food when the patch border is reached. Therefore, by adapting different elements in their foraging behavior, larvae either increase the time inside nutritious food patches or continue exploring the substrate in less nutritious environments.
Assessing the utility of CASP14 models for molecular replacement
Authors: Millán Claudia , Keegan Ronan M. , Pereira Joana , Sammito Massimo D. , Simpkin Adam J. , McCoy Airlie J. , Lupas Andrei N. , Hartmann Marcus D. , Rigden Daniel J. , Read Randy J.
Published: June 2021

The assessment of CASP models for utility in molecular replacement is a measure of their use in a valuable real-world application. In CASP7, the metric for molecular replacement assessment involved full likelihood-based molecular replacement searches; however, this restricted the assessable targets to crystal structures with only one copy of the target in the asymmetric unit, and to those where the search found the correct pose. In CASP10, full molecular replacement searches were replaced by likelihood-based rigid-body refinement of models superimposed on the target using the LGA algorithm, with the metric being the refined likelihood (LLG) score. This enabled multi-copy targets and very poor models to be evaluated, but a significant further issue remained: the requirement of diffraction data for assessment. We introduce here the relative-expected-LLG (reLLG), which is independent of diffraction data. This reLLG is also independent of any crystal form, and can be calculated regardless of the source of the target, be it X-ray, NMR or cryo-EM. We calibrate the reLLG against the LLG for targets in CASP14, showing that it is a robust measure of both model and group ranking. Like the LLG, the reLLG shows that accurate coordinate error estimates add substantial value to predicted models. We find that refinement by CASP groups can often convert an inadequate initial model into a successful MR search model. Consistent with findings from others, we show that the AlphaFold2 models are sufficiently good, and reliably so, to surpass other current model generation strategies for attempting molecular replacement phasing.
Changes in dynamic transitions between integrated and segregated states underlie visual hallucinations in Parkinson’s disease
Authors: Zarkali Angeliki , Luppi Andrea I. , Stamatakis Emmanuel A. , Reeves Suzanne , McColgan Peter , Leyland Louise-Ann , Lees Andrew J. , Weil Rimona S.
Published: June 2021

Background

Visual hallucinations in Parkinsons disease (PD) are transient, suggesting a change in dynamic brain states. However, the causes underlying these dynamic brain changes are not known.

Methods

Focusing on fundamental network properties of integration and segregation, we used rsfMRI to examine alterations in temporal dynamics in PD patients with hallucinations (n=16) compared to those without hallucinations (n=75) and a group of normal controls (n=32). We used network control theory to examine how structural connectivity guides transitions between functional states. We then studied the brain regions most involved in these state transitions, and examined corresponding neurotransmitter density profiles and receptor gene expression in health.

Results

There were significantly altered temporal dynamics in PD with hallucinations, with an increased proportion of time spent in the Segregated state compared to non-hallucinators and controls; less between-state transitions; and increased dwell time in the Segregated state. The energy cost needed to transition from integrated-to-segregated state was lower in PD-hallucinators compared to non-hallucinators. This was primarily driven by subcortical and transmodal cortical brain regions, including the thalamus and default mode network regions. The regional energy needed to transition from integrated-to-segregated state was significantly correlated with regional neurotransmitter density and gene expression profiles for serotoninergic (including 5HT2A), GABAergic, noradrenergic and cholinergic but not dopaminergic density profiles.

Conclusions

We describe the patterns of temporal functional dynamics in PD-hallucinations, and link these with neurotransmitter systems involved in early sensory and complex visual processing. Our findings provide mechanistic insights into visual hallucinations in PD and highlighting potential therapeutic targets.
Negative online reviews, brand equity and emotional contagion
Authors: Ahmad Fayez , Guzmán Francisco
Published: June 2021

Purpose

Despite the growing consensus that consumers extensively use online reviews and that negative reviews can significantly damage brand equity, it remains uncertain whether negative online reviews that focus on different aspects of a service have a similar or differential effect on brand equity. This study aims to fill this gap and explores the mediating role of emotional contagion and what kind of response helps better deter their negative effect.

Design/methodology/approach

This research is conducted through a one-panel study and three experimental studies. SAS enterprise miner is used for text mining analysis and Analysis of variance (ANOVA) and Process macro models are used to analyze the experimental data.

Findings

Negative reviews related to the tangibility, responsiveness and empathy dimensions have a more detrimental effect on brand equity than negative reviews related to the assurance and reliability dimensions. The results also provide evidence that emotional contagion is more prevalent when consumers read reviews that are specific to the empathy and responsiveness dimensions. Finally, accommodative responses from the service provider are more effective in deterring the effect of a negative online review on brand equity.

Research limitations/implications

The generalizability of this study is limited to the restaurant and hotel industry.

Practical implications

The findings will also help the brand manager in understanding the comparative effect of service quality-specific negative reviews on brand equity and also the type of responses that brand managers should give to negative reviews.

Originality/value

Despite online reviews receiving increased attention in academic research, Service quality (SERVQUAL) dimension-specific reviews have not been studied until now. This study contributes to the service quality-related literature by providing evidence that not all negative online reviews related to different Service quality (SERVQUAL) dimensions equally affect brand equity.
Financial support services for beekeepers: a case study of development interventions in Fiji's Northern Division
Authors: Hinton Jordanna , Schouten Cooper , Stimpson Kerrie , Lloyd David
Published: June 2021

Purpose

This paper analyses financial support services (loans and grants) from the perspective of beekeepers in Fiji's Northern Division.

Design/methodology/approach

A mixed-method, case study approach was used with key informant interviews, focus groups, semi-structured interviews and questionnaires.

Findings

Financial support was found to be an appropriate intervention. While beekeepers have access to loans, matching grants or small business grants to assist the establishment and growth of their activities, the appropriateness of these services varies based on the experience and skill of beekeepers. Capacity building was an important shortcoming in all financial services. It is recommended beekeeping clients undertake outcome-based, practical and/or mentorship-styled training to ensure beekeepers have the appropriate skills to maintain a viable enterprise.

Research limitations/implications

This study was limited by a small sample size. Further research is needed to understand long-term impacts of financial support services and the availability and appropriateness of these within and between regions.

Social implications

Recommendations are provided to encourage effective financial support for beekeepers to improve the productivity, profitability and sustainability of their activities. This can impact beekeepers' livelihoods by increasing household income and income security.

Originality/value

There is a paucity of literature on the effectiveness of financial interventions to support beekeeping enterprises. This is the first study to compare financial support services from the perspective of beekeepers in the Pacific region.
A robust sequencing assay of a thousand amplicons for the high‐throughput population monitoring of Alpine ibex immunogenetics
Authors: Kessler Camille , Brambilla Alice , Waldvogel Dominique , Camenisch Glauco , Biebach Iris , Leigh Deborah M. , Grossen Christine , Croll Daniel
Published: June 2021

Polymorphism for immune functions can explain significant variation in health and reproductive success within species. Drastic loss in genetic diversity at such loci constitutes an extinction risk and should be monitored in species of conservation concern. However, effective implementations of genome‐wide immune polymorphism sets into high‐throughput genotyping assays are scarce. Here, we report the design and validation of a microfluidics‐based amplicon sequencing assay to comprehensively capture genetic variation in Alpine ibex (Capra ibex). This species represents one of the most successful large mammal restorations recovering from a severely depressed census size and a massive loss in diversity at the major histocompatibility complex (MHC). We analysed 65 whole‐genome sequencing sets of the Alpine ibex and related species to select the most representative markers and to prevent primer binding failures. In total, we designed ~1,000 amplicons densely covering the MHC, further immunity‐related genes as well as randomly selected genome‐wide markers for the assessment of neutral population structure. Our analysis of 158 individuals shows that the genome‐wide markers perform equally well at resolving population structure as RAD‐sequencing or low‐coverage genome sequencing data sets. Immunity‐related loci show unexpectedly high degrees of genetic differentiation within the species. Such information can now be used to define highly targeted individual translocations. Our design strategy can be realistically implemented into genetic surveys of a large range of species. In conclusion, leveraging whole‐genome sequencing data sets to design targeted amplicon assays allows the simultaneous monitoring of multiple genetic risk factors and can be translated into species conservation recommendations.
Application of 3D Static Modelling in Reservoir Characterization: A Case Study from the Qishn Formation in Sharyoof Oil Field, Masila Basin, Yemen
Authors: ABDULLAH Emad A. , ABDELMAKSOUD Ahmed , HASSAN Musab A.
Published: June 2021

Three‐dimensional (3D) static modelling techniques are applied to the characterization of the Qishn Formation (Fm.) in the Sharyoof oil field locating within the Masila basin, southeastern Yemen. The present study was initiated by the seismic structural interpretation, followed by building a 3D structural framework, in addition to analysing well log data and from these, 3D facies and petrophysical models are constructed. In the Sharyoof oil field, the Qishn Fm. exhibits depth values within the range of 400–780 m below sea level, with a general increase towards the SSE. A set of high dip angle normal faults with a general ENE–WSW trend dissect the rocks. The strata are also folded as a main anticline with an axis that is parallel to the fault trend, formed as a result of basement uplift. According to the facies models, the Qishn Fm. comprises 43.83% limestone, 21.53% shale, 21.26% sandstone, 13.21% siltstone and 0.17% dolomite. The Qishn Carbonates Member has low porosity values making it a potential seal for the underlying reservoirs whereas the Upper Qishn Clastics S1A and C have good reservoir quality and S1B has fair reservoir quality. The Upper Qishn Clastics S2 and S3 also have fair reservoir quality, while the Lower Qishn Clastics zone has good reservoir quality. The water saturation decreases towards the west and east and increases towards north and south. The total original oil in‐place (OOIP) of the Upper Qishn clastics is 106 million STB within the S1A, S1C and S2 zones. Drilling of development wells is recommended in the eastern study area, where good trapping configuration is exhibited in addition to the presence of a potential seal (Upper Qishn Carbonates Member) and reservoir (Qishn Clastics Member) with high porosity and low water saturation.
Prediction of Shale Gas Pressure based on Multi‐channel Seismic Inversion in Fuling
Authors: XING Lei , LI Yu , LI Qianqian , LIU Yaowen , WAN Yunqiang , YANG Huiliang
Published: June 2021

The accurate prediction of formation pressure is important in oil/gas exploration and development. However, the achievement of this goal remains challenging, due to insufficient logging data and the low predictive data accuracy from seismic data. In this work, a case study was carried out in the Baima area of Wulong, in order to develop a workflow for accurately predicting shale gas formation pressure. The multi‐channel stack method was first used, as well as the inversion of single‐channel seismic data, to construct velocity and density models of the formation. Combined with the existing well‐logging data, the velocity and density models of the whole well section were established. The shale gas formation pressure was then estimated using the Eaton method. The results show that the multi‐channel seismic stacking method has a higher accuracy than the inversion of the formation velocity obtained by the single‐channel seismic method. The discrepancies between our predicted formation pressure and the actual formation pressure measurement are within an acceptable range, indicating that our workflow is effective.
First Record ofPetalodusOwen, 1840 (Chondrichthyes, Petalodontidae) in the Lower Permian (Cisuralian) of China
Authors: GAI Zhikun , BAI Zhijun , LIN Xianghong , MENG Xinyuan , ZHANG Junwen
Published: June 2021

The Petalodontiformes are a small intriguing group of Permo–Carboniferous chondrichthyans.Petalodusis the longest known petalodont genus generally considered representative of the order. The first definite fossil record of seven well‐preservedPetalodusteeth has been found in the Qianshi limestone in the Lower Permian (Cisuralian) middle–upper Taiyuan Formation in Yangquan City, Shanxi Province, North China. The specimens are characterized by petal‐shaped teeth with a spade‐like crown, and a long, tongue‐shaped root; the crown is circled with a band or cingulum composed of imbricated ridges at the base. All seven teeth are assigned to the speciesP. ohioenesisbecause of their vertically narrow cingulum and much longer root.Petalodusis a worldwide genus, with fossil localities mainly concentrated in the Laurussia supercontinent. The occurrence ofPetalodusteeth in Yangquan not only is the first fossil record in China, but also only the second record in Asia. The Yangquan fossil site was part of the paleoequatorial North China Craton during the Early Permian, and was isolated from Laurusia and East Gondwana by the Paleo‐Tethys Ocean. The successful dispersal ofPetalodusfrom Laurusia to the North China Block along Paleo‐Tethys may support the possibility thatPetalodustaxa were active free‐swimmers rather than bottom dwellers. The new finding increases the petalodont diversity in eastern Asia, and also sheds new light on the distribution and stratigraphic range.
Making Unequal Democracy Work? The Effects of Income on Voter Turnout in Northern Italy
Authors: Schafer Jerome , Cantoni Enrico , Bellettini Giorgio , Berti Ceroni Carlotta
Published: June 2021

In many democracies, voter turnout is higher among the rich than the poor. But do changes in income lead to changes in electoral participation? We address this question with unique administrative data matching a decade of individual tax records with voter rolls in a large municipality in northern Italy. We document several important findings. First, levels of income and turnout both dropped disproportionately among relatively poor citizens following the Great Recession. Second, we show that within‐individual changes in income have an effect on participation, which is modest on average due to diminishing returns, but can be consequential among the poor. Third, we find that declining turnout of voters facing economic insecurity has exacerbated the income skew in participation, suggesting that income inequality and turnout inequality may reinforce each other. We discuss the theoretical implications of these results, set in a context with strong civic traditions and low barriers to voting.
Change We Can Believe In: Structural and Content Dynamics within Belief Networks
Authors: Fishman Nic , Davis Nicholas T.
Published: June 2021

Scholars have used network analysis to explore the structural properties of mass ideology. This article incorporates two important, though ignored features in past research by investigating howtimeshapes the properties of belief networksfor different populations of people—those who exhibit high and low levels of political knowledge. We find that (1) belief network density increases asymmetrically among people with high relative to low knowledge; (2) symbolic preferences are more central to belief networks irrespective of survey timing or population; in contrast, policy beliefs exhibit some increase in centrality over time among the politically knowledgeable; and (3) a belief's centrality is unrelated to the amount of change it explains in other beliefs. Troublingly, this latter finding presents problems for describing belief networks using the vernacular of Conversian belief systems—a disconnect that seems grounded in the mismatch between Converse's individual‐level theory and network analysis' population‐based properties.