bluuebunny/crossref_metadata_2025 huggingface dataset:
Eliminating accidental deviations to minimize generalization error and maximize replicability: Applications in connectomics and genomics
Authors: Bridgeford Eric W. , Wang Shangsi , Wang Zeyi , Xu Ting , Craddock Cameron , Dey Jayanta , Kiar Gregory , Gray-Roncal William , Colantuoni Carlo , Douville Christopher , Noble Stephanie , Priebe Carey E. , Caffo Brian , Milham Michael , Zuo Xi-Nian ,   Consortium for Reliability and Reproducibility, Vogelstein Joshua T.
Published: September 2021

Replicability, the ability to replicate scientific findings, is a prerequisite for scientific discovery and clinical utility. Troublingly, we are in the midst of a replicability crisis. A key to replicability is that multiple measurements of the same item (e.g., experimental sample or clinical participant) under fixed experimental constraints are relatively similar to one another. Thus, statistics that quantify the relative contributions of accidental deviations—such as measurement error—as compared to systematic deviations—such as individual differences—are critical. We demonstrate that existing replicability statistics, such as intra-class correlation coefficient and fingerprinting, fail to adequately differentiate between accidental and systematic deviations in very simple settings. We therefore propose a novel statistic, discriminability, which quantifies the degree to which an individual’s samples are relatively similar to one another, without restricting the data to be univariate, Gaussian, or even Euclidean. Using this statistic, we introduce the possibility of optimizing experimental design via increasing discriminability and prove that optimizing discriminability improves performance bounds in subsequent inference tasks. In extensive simulated and real datasets (focusing on brain imaging and demonstrating on genomics), only optimizing data discriminability improves performance on all subsequent inference tasks for each dataset. We therefore suggest that designing experiments and analyses to optimize discriminability may be a crucial step in solving the replicability crisis, and more generally, mitigating accidental measurement error.
On cross-ancestry cancer polygenic risk scores
Authors: Fritsche Lars G. , Ma Ying , Zhang Daiwei , Salvatore Maxwell , Lee Seunggeun , Zhou Xiang , Mukherjee Bhramar
Published: September 2021

Polygenic risk scores (PRS) can provide useful information for personalized risk stratification and disease risk assessment, especially when combined with non-genetic risk factors. However, their construction depends on the availability of summary statistics from genome-wide association studies (GWAS) independent from the target sample. For best compatibility, it was reported that GWAS and the target sample should match in terms of ancestries. Yet, GWAS, especially in the field of cancer, often lack diversity and are predominated by European ancestry. This bias is a limiting factor in PRS research. By using electronic health records and genetic data from the UK Biobank, we contrast the utility of breast and prostate cancer PRS derived from external European-ancestry-based GWAS across African, East Asian, European, and South Asian ancestry groups. We highlight differences in the PRS distributions of these groups that are amplified when PRS methods condense hundreds of thousands of variants into a single score. While European-GWAS-derived PRS were not directly transferrable across ancestries on an absolute scale, we establish their predictive potential when considering them separately within each group. For example, the top 10% of the breast cancer PRS distributions within each ancestry group each revealed significant enrichments of breast cancer cases compared to the bottom 90% (odds ratio of 2.81 [95%CI: 2.69,2.93] in European, 2.88 [1.85, 4.48] in African, 2.60 [1.25, 5.40] in East Asian, and 2.33 [1.55, 3.51] in South Asian individuals). Our findings highlight a compromise solution for PRS research to compensate for the lack of diversity in well-powered European GWAS efforts while recruitment of diverse participants in the field catches up.
Aedes albopictus bionomics data collection by citizen participation on Procida Island, a promising Mediterranean site for the assessment of innovative and community-based integrated pest management methods
Authors: Caputo Beniamino , Langella Giuliano , Petrella Valeria , Virgillito Chiara , Manica Mattia , Filipponi Federico , Varone Marianna , Primo Pasquale , Puggioli Arianna , Bellini Romeo , D’Antonio Costantino , Iesu Luca , Tullo Liliana , Rizzo Ciro , Longobardi Annalisa , Sollazzo Germano , Perrotta Maryanna Martina , Fabozzi Miriana , Palmieri Fabiana , Saccone Giuseppe , Rosà Roberto , della Torre Alessandra , Salvemini Marco
Published: September 2021

In the last decades, the colonization of Mediterranean Europe and of other temperate regions by Aedes albopictus created an unprecedented nuisance problem in highly infested areas and new public health threats due to the vector competence of the species. The Sterile Insect Technique (SIT) and the Incompatible Insect Technique (IIT) are insecticide-free mosquito-control methods, relying on mass release of irradiated/manipulated males, able to complement existing and only partially effective control tools. The validation of these approaches in the field requires appropriate experimental settings, possibly isolated to avoid mosquito immigration from other infested areas, and preliminary ecological and entomological data. We carried out a 4-year study in the island of Procida (Gulf of Naples, Italy) in strict collaboration with local administrators and citizens to estimate the temporal dynamics, spatial distribution, and population size of Ae. albopictus and the dispersal and survival of irradiated males. We applied ovitrap monitoring, geo-spatial analyses, mark-release-recapture technique, and a citizen-science approach. Results allow to predict the seasonal (from April to October, with peaks of 928–9,757 males/ha) and spatial distribution of the species, highlighting the capacity of Ae. albopictus population of Procida to colonize and maintain high frequencies in urban as well as in sylvatic inhabited environments. Irradiated males shown limited ability to disperse (mean daily distance travelled <60m) and daily survival estimates ranging between 0.80 and 0.95. Overall, the ecological characteristics of the island, the acquired knowledge on Ae. albopictus spatial and temporal distribution, the high human and Ae. albopictus densities and the positive attitude of the resident population in being active parts in innovative mosquito control projects provide the ground for evidence-based planning of the interventions and for the assessment of their effectiveness. In addition, the results highlight the value of creating synergies between research groups, local administrators, and citizens for affordable monitoring (and, in the future, control) of mosquito populations.
High prevalence of Schistosoma japonicum by perfusion in naturally exposed water buffalo in a region of the Philippines endemic for human schistosomiasis
Authors: Jiz Mario , Mingala Claro , Fu Zhi-Qiang , Adriatico Melika , Lu Ke , Jarilla Blanca , Sagliba Marianne , Moreno Ammabelle , Park Sangshin , Lin Jiao-Jiao , Olveda Remigio , Kurtis Jonathan D. , Wu Hannah W.
Published: September 2021

In the past decade, ecological surveys emphasized rats and dogs as the most significant animal reservoirs for Schistosoma japonicum (S.j) in the Philippines. However, recent studies demonstrated 51–91% prevalence of schistosomiasis among water buffalo using qPCR in the Sj endemic regions in the Philippines. In order to resolve the inconsistency of reported surveys regarding Sj endemicity among carabao, a domestic water buffalo that is the most important draught animal, we introduced 42 schistosome negative water buffalo to Macanip, Jaro municipality, Leyte, the Philippines, a subsistence rice-farming village that has been the focus of schistosomiasis japonica studies of our group for the past 20 years. We conducted perfusion to the remaining 34 buffalo that survived 10 months of nature exposure and Typhoon Haiyan. Thirty-three water buffalo were found to be positive with at least 1 pair of worms from the mesenteric vein. The infection rate is 97%, with the worm burden of 94 (95% confidence interval, 49–138 worms) worms. To our knowledge, this is the first report about S. japonicum worm burden in naturally infected water buffalo in the Philippines. The fact that with less than one-year of exposure, in this human schistosomiasis endemic area, only 1 out of 34 water buffalo was uninfected is striking. Urgent attention is needed for a cost-effective technique for monitoring Sj infection in animals and humans. Meanwhile, intervention implementation, including water buffalo treatment and vaccination, should be taken into consideration.
Erosion and deposition vulnerability of small (<5,000 km2) tropical islands
Authors: Browning Trevor N. , Sawyer Derek E.
Published: September 2021

The tropics are naturally vulnerable to watershed erosion. This region is rapidly growing (projected to be 50% of the global population by 2050) which exacerbates erosional issues by the subsequent land use change. The issue is particularly of interest on the many (~45,000) small tropical (<5,000 km2) islands, and their >115M residents, where ecotourism and sediment intolerant ecosystems such as coral reefs are the main driver of their economies. However, vulnerability to erosion and deposition is poorly quantified in these regions due to the misclassification or exclusion of small islands in coarse global analyses. We use the only vulnerability assessment method that connects watershed erosion and coastal deposition to compare locally sourced, high-resolution datasets (5 x 5 m) to satellite-collected, remotely sensed low-resolution datasets (463 x 463 m). We find that on the island scale (~52 km2) the difference in vulnerability calculated by the two methods is minor. On the watershed scale however, low-resolution datasets fail to accurately demonstrate watershed and coastal deposition vulnerability when compared to high-resolution analysis. Specifically, we find that anthropogenic development (roads and buildings) is poorly constrained at a global scale. Structures and roads are difficult to identify in heavily forested regions using satellite algorithms and the rapid, ongoing rate of development aggravates the issue. We recommend that end-users of this method obtain locally sourced anthropogenic development datasets for the best results while using low resolution datasets for the other variables. Fortunately, anthropogenic development data can be easily collected using community-based research or identified using satellite imagery by any level of user. Using high-resolution results, we identify a development trend across St. John and regions that are both high risk and possible targets for future development. Previously published modeled and measured sedimentation rates demonstrate the method is accurate when using low-resolution or high-resolution data but, anthropogenic development, watershed slope, and earthquake probability datasets should be of the highest resolution depending on the region specified.
Phase and power modulations on the amplitude of TMS-induced motor evoked potentials
Authors: Schilberg Lukas , Ten Oever Sanne , Schuhmann Teresa , Sack Alexander T.
Published: September 2021

The evaluation of transcranial magnetic stimulation (TMS)-induced motor evoked potentials (MEPs) promises valuable information about fundamental brain related mechanisms and may serve as a diagnostic tool for clinical monitoring of therapeutic progress or surgery procedures. However, reports about spontaneous fluctuations of MEP amplitudes causing high intra-individual variability have led to increased concerns about the reliability of this measure. One possible cause for high variability of MEPs could be neuronal oscillatory activity, which reflects fluctuations of membrane potentials that systematically increase and decrease the excitability of neuronal networks. Here, we investigate the dependence of MEP amplitude on oscillation power and phase by combining the application of single pulse TMS over the primary motor cortex with concurrent recordings of electromyography and electroencephalography. Our results show that MEP amplitude is correlated to alpha phase, alpha power as well as beta phase. These findings may help explain corticospinal excitability fluctuations by highlighting the modulatory effect of alpha and beta phase on MEPs. In the future, controlling for such a causal relationship may allow for the development of new protocols, improve this method as a (diagnostic) tool and increase the specificity and efficacy of general TMS applications.
Biomedical graduate student experiences during the COVID-19 university closure
Authors: Varadarajan Janani , Brown Abigail M. , Chalkley Roger
Published: September 2021

COVID-19-associated university closures moved classes online and interrupted ongoing research in universities throughout the US. In Vanderbilt University, first year biomedical sciences PhD students were in the middle of their spring semester coursework and in the process of identifying a thesis research lab, while senior students who had already completed the first year were at various stages of their graduate training and were working on their thesis research projects. To learn how the university closure and resulting interruptions impacted our students’ learning and well-being, we administered two surveys, one to the first year students and the other to the senior students. Our main findings show that the university closure negatively impacted the overall psychological health of about one-third of the survey respondents, time management was the aspect of remote learning that caused the highest stress for close to 50% of the students, and interaction with their peers and in-person discussions were the aspects of on-campus learning that students missed the most during the remote learning period. Additionally, survey responses also show that students experienced positive outcomes as a result of remote learning that included spending increased time on additional learning interests, with family, on self-care, and for dissertation or manuscript writing. Though a variety of supportive resources are already available to students in our institution, results from our survey suggest enhancing these measures and identifying new ones targeted to addressing the academic and emotional needs of PhD students would be beneficial. Such support measures may be appropriate for students in other institutions as well.
The role of local impedance drop in the acute lesion efficacy during pulmonary vein isolation performed with a new contact force sensing catheter—A pilot study
Authors: Szegedi Nándor , Salló Zoltán , Perge Péter , Piros Katalin , Nagy Vivien Klaudia , Osztheimer István , Merkely Béla , Gellér László
Published: September 2021

Introduction

Our pilot study aimed to evaluate the role of local impedance drop in lesion formation during pulmonary vein isolation with a novel contact force sensing ablation catheter that records local impedance as well and to find a local impedance cut-off value that predicts successful lesion formation.

Materials and methods

After completing point-by-point radiofrequency pulmonary vein isolation, the success of the applications was evaluated by pacing along the ablation line at 10 mA, 2 ms pulse width. Lesions were considered successful if loss of local capture was achieved.

Results

Out of 645 applications, 561 were successful and 84 were unsuccessful. Compared to the unsuccessful ablation points, the successful applications were shorter (p = 0.0429) and had a larger local impedance drop (p<0.0001). There was no difference between successful and unsuccessful applications in terms of mean contact force (p = 0.8571), force-time integral (p = 0.0699) and contact force range (p = 0.0519). The optimal cut-point for the local impedance drop indicating successful lesion formation was 21.80 Ohms on the anterior wall [AUC = 0.80 (0.75–0.86), p<0.0001], and 18.30 Ohms on the posterior wall [AUC = 0.77 (0.72–0.83), p<0.0001]. A local impedance drop larger than 21.80 Ohms on the anterior wall and 18.30 Ohms on the posterior wall was associated with an increased probability of effective lesion creation [OR = 11.21, 95%CI 4.22–29.81, p<0.0001; and OR = 7.91, 95%CI 3.77–16.57, p<0.0001, respectively].

Conclusion

The measurement of the local impedance may predict optimal lesion formation. A local impedance drop > 21.80 Ohms on the anterior wall and > 18.30 Ohms on the posterior wall significantly increases the probability of creating a successful lesion.
Comparison of the internal fit of metal crowns fabricated by traditional casting, computer numerical control milling, and three-dimensional printing
Authors: Chou Wei-Ting , Chuang Chuan-Chung , Wang Yi-Bing , Chiu Hsien-Chung
Published: September 2021

This experimental study aimed to compare the internal fit (marginal fit and internal discrepancy) of metal crowns fabricated by traditional casting and digital methods (computer numerically controlled (CNC) milling and three-dimensional [3D] printing). Thirty standard master abutment models were fabricated using a 3D printing technique with digital software. Metal crowns were fabricated by traditional casting, CNC milling, and 3D printing. The silicon replica method was used to measure the marginal and internal fit. A thin layer of low-viscosity polyvinyl siloxane material was placed inside each crown and on the die (like a seat) until the material was set. Replicas were examined at four reference points under a microscope: the central pit (M1), cusp tip (M2), axial wall (M3), and margin (M4). The measured data were analyzed using a one-way analysis of variance (ANOVA) to verify statistical significance, which was set at p < 0.05. In the traditional casting group, the minimum distance measured was at M3 (90.68 ± 14.4 μm) and the maximum distance measured was at M1 (145.12 ± 22 μm). In the milling group, the minimum distance measured was at M3 (71.85 ± 23.69 μm) and the maximum distance measured was at M1 (108.68 ± 10.52 μm). In the 3D printing group, the minimum distance measured was at M3 (100.59 ± 9.26 μm) and the maximum distance measured was at M1 (122.33 ± 7.66 μm). The mean discrepancy for the traditional casting, CNC milling, and 3D printing groups was 120.20, 92.15, and 111.85 μm, respectively, showing significant differences (P < 0.05). All three methods of metal crown fabrication, that is, traditional casting, CNC milling, and 3D printing, had values within the clinically acceptable range. The marginal and internal fit of the crown was far superior in the CNC milling method.
Relay oral therapy in febrile urinary tract infections caused by extended spectrum beta-lactamase–producing Enterobacteriaceae in children: A French multicenter study
Authors: Lignieres Gabriel , Birgy André , Jung Camille , Bonacorsi Stéphane , Levy Corinne , Angoulvant François , Grimprel Emmanuel , Dommergues Marie Aliette , Gillet Yves , Craiu Irina , Rybak Alexis , De Pontual Loic , Dubos François , Cixous Emmanuel , Gajdos Vincent , Pinquier Didier , Andriantahina Isabelle , Soussan-Banini Valérie , Georget Emilie , Launay Elise , Vignaud Olivier , Cohen Robert , Madhi Fouad
Published: September 2021

Objectives

We need studies assessing therapeutic options for oral relay in febrile urinary tract infection (FUTI) due to ESBL–producing Enterobacteriaceae (ESBL-E) in children. Amoxicillin-clavulanate/cefixime (AC-cefixime) combination seems to be a suitable option. We sought to describe the risk of recurrence at 1 month after the end of treatment for FUTI due to ESBL-E according to the oral relay therapy used.

Materials and methods

We retrospectively identified children <18 years who were included in a previous prospective observational multicentric study on managing FUTI due to ESBL-E between 2014 and 2017 in France. We collected whether children who received cotrimoxazole, ciprofloxacin or the AC-cefixime combination as the oral relay therapy reported a recurrence within the first month after the end of treatment. Then, we analyzed the susceptibility drug-testing of the strains involved.

Results

We included 199 children who received an oral relay therapy with cotrimoxazole (n = 72, 36.2%), ciprofloxacin (n = 38, 19.1%) or the AC-cefixime combination (n = 89, 44.7%). Nine (4.5%) patients had a recurrence within the first month after the end of treatment, with no difference between the 3 groups of oral relay (p = 0.8): 4 (5.6%) cotrimoxazole, 2 (5.3%) ciprofloxacin and 3 (3.4%) AC-cefixime combination. Phenotype characterization of 249 strains responsible for FUTI due to ESBL-E showed that 97.6% were susceptible to the AC-cefixime combination.

Conclusions

The AC-cefixime combination represents an interesting therapeutic option for oral relay treatment of FUTI due to ESBL-E as the recurrence rate at 1 month after the end of treatment was the same when compared to cotrimoxazole and ciprofloxacin.
Accuracy of perceived glaucoma risk by patients in a clinical setting
Authors: Hou Chiun-Ho , Lee Jiahn-Shing , Lin Ken-Kuo , Liu Laura , Lee Yung-Sung , Pu Christy
Published: September 2021

Objective

To determine whether patients attending the ophthalmology department underestimate their glaucoma risks.

Method

We conducted a cross-sectional survey with a final study population of 1203 individuals from two medical centers in Taiwan during January 1–June 30, 2019. The “High concern” group was defined as the set of patients who rated themselves as having low risk but who had been rated by physicians as having medium or high risk of developing glaucoma over the next year.

Results

Approximately 12% of the respondents belonged to the “High concern” group. For those with education at the college level or higher, the interaction term was estimated to be 0.294 (95% CI = 0.136–0.634). Marginal effect calculations revealed significant sex-based differences in the effect of knowledge at specific age intervals.

Conclusions

A considerable proportion of patients attending the ophthalmology department underestimate their glaucoma risks. Misjudgment of glaucoma risks can lead to delays in seeking of medical attention. Glaucoma education should be designed according to each patient’s education level and sex, as its effect is not consistent across different education and sex clusters.
Genetic differentiation of mainland-island sheep of Greece: Implications for identifying candidate genes for long-term local adaptation
Authors: Kominakis Antonios , Tarsani Eirini , Hager-Theodorides Ariadne L. , Mastranestasis Ioannis , Gkelia Dimitra , Hadjigeorgiou Ioannis
Published: September 2021

In Greece, a number of local sheep breeds are raised in a wide range of ecological niches across the country. These breeds can be used for the identification of genetic variants that contribute to local adaptation. To this end, 50k genotypes of 90 local sheep from mainland Greece (Epirus, n = 35 and Peloponnesus, n = 55) were used, as well as 147 genotypes of sheep from insular Greece (Skyros, n = 21), Lemnos, n = 36 and Lesvos, n = 90). Principal components and phylogenetic analysis along with admixture and spatial point patterns analyses suggested genetic differentiation of ‘mainland-island’ populations. Genome scans for signatures of selection and genome-wide association analysis (GWAS) pointed to one highly differentiating marker on OAR4 (FST= 0.39, FLK = 21.93, FDR p-value = 0.10) that also displayed genome wide significance (FDR p-value = 0.002) during GWAS. A total number of 6 positional candidate genes (LOC106990429,ZNF804B,TEX47,STEAP4,SRI and ADAM22) were identified within 500 kb flanking regions around the significant marker. In addition, two QTLs related to fat tail deposition are reported in genomic regions 800 kb downstream the significant marker. Based on gene ontology analysis and literature evidence, the identified candidate genes possess biological functions relevant to local adaptation that worth further investigation.
WHotLAMP: A simple, inexpensive, and sensitive molecular test for the detection of SARS-CoV-2 in saliva
Authors: Ng David , Pinharanda Ana , Vogt Merly C. , Litwin-Kumar Ashok , Stearns Kyle , Thopte Urvashi , Cannavo Enrico , Enikolopov Armen , Fiederling Felix , Kosmidis Stylianos , Noro Barbara , Rodrigues-Vaz Ines , Shayya Hani , Andolfatto Peter , Peterka Darcy S. , Tabachnik Tanya , D’Armiento Jeanine , Goldklang Monica , Bendesky Andres
Published: September 2021

Despite the development of effective vaccines against SARS-CoV-2, epidemiological control of the virus is still challenging due to slow vaccine rollouts, incomplete vaccine protection to current and emerging variants, and unwillingness to get vaccinated. Therefore, frequent testing of individuals to identify early SARS-CoV-2 infections, contact-tracing and isolation strategies remain crucial to mitigate viral spread. Here, we describe WHotLAMP, a rapid molecular test to detect SARS-CoV-2 in saliva. WHotLAMP is simple to use, highly sensitive (~4 viral particles per microliter of saliva) and specific, as well as inexpensive, making it ideal for frequent screening. Moreover, WHotLAMP does not require toxic chemicals or specialized equipment and thus can be performed in point-of-care settings, and may also be adapted for resource-limited environments or home use. While applied here to SARS-CoV-2, WHotLAMP can be modified to detect other pathogens, making it adaptable for other diagnostic assays, including for use in future outbreaks.
Pilot study on the value of Raman spectroscopy in the entity assignment of salivary gland tumors
Authors: Meyer Till Jasper , Gerhard-Hartmann Elena , Lodes Nina , Scherzad Agmal , Hagen Rudolf , Steinke Maria , Hackenberg Stephan
Published: September 2021

Background

The entity assignment of salivary gland tumors (SGT) based on histomorphology can be challenging. Raman spectroscopy has been applied to analyze differences in the molecular composition of tissues. The aim of this study was to evaluate the suitability of RS for entity assignment in SGT.

Methods

Raman data were collected in deparaffinized sections of pleomorphic adenomas (PA) and adenoid cystic carcinomas (ACC). Multivariate data and chemometric analysis were completed using the Unscrambler software.

Results

The Raman spectra detected in ACC samples were mostly assigned to nucleic acids, lipids, and amides. In a principal component-based linear discriminant analysis (LDA) 18 of 20 tumor samples were classified correctly.

Conclusion

In this proof of concept study, we show that a reliable SGT diagnosis based on LDA algorithm appears possible, despite variations in the entity-specific mean spectra. However, a standardized workflow for tissue sample preparation, measurement setup, and chemometric algorithms is essential to get reliable results.
Modelling and optimal control of multi strain epidemics, with application to COVID-19
Authors: Arruda Edilson F. , Das Shyam S. , Dias Claudia M. , Pastore Dayse H.
Published: September 2021

Reinfection and multiple viral strains are among the latest challenges in the current COVID-19 pandemic. In contrast, epidemic models often consider a single strain and perennial immunity. To bridge this gap, we present a new epidemic model that simultaneously considers multiple viral strains and reinfection due to waning immunity. The model is general, applies to any viral disease and includes an optimal control formulation to seek a trade-off between the societal and economic costs of mitigation. We validate the model, with and without mitigation, in the light of the COVID-19 epidemic in England and in the state of Amazonas, Brazil. The model can derive optimal mitigation strategies for any number of viral strains, whilst also evaluating the effect of distinct mitigation costs on the infection levels. The results show that relaxations in the mitigation measures cause a rapid increase in the number of cases, and therefore demand more restrictive measures in the future.
Infection with endosymbiotic Spiroplasma disrupts tsetse (Glossina fuscipes fuscipes) metabolic and reproductive homeostasis
Authors: Son Jae Hak , Weiss Brian L. , Schneider Daniela I. , Dera Kiswend-sida M. , Gstöttenmayer Fabian , Opiro Robert , Echodu Richard , Saarman Norah P. , Attardo Geoffrey M. , Onyango Maria , Abd-Alla Adly M. M. , Aksoy Serap
Published: September 2021

Tsetse flies (Glossinaspp.) house a population-dependent assortment of microorganisms that can include pathogenic African trypanosomes and maternally transmitted endosymbiotic bacteria, the latter of which mediate numerous aspects of their host’s metabolic, reproductive, and immune physiologies. One of these endosymbionts,Spiroplasma, was recently discovered to reside within multiple tissues of field captured and laboratory colonized tsetse flies grouped in the Palpalis subgenera. In various arthropods,Spiroplasmainduces reproductive abnormalities and pathogen protective phenotypes. In tsetse,Spiroplasmainfections also induce a protective phenotype by enhancing the fly’s resistance to infection with trypanosomes. However, the potential impact ofSpiroplasmaon tsetse’s viviparous reproductive physiology remains unknown. Herein we employed high-throughput RNA sequencing and laboratory-based functional assays to better characterize the association betweenSpiroplasmaand the metabolic and reproductive physiologies ofG.fuscipes fuscipes(Gff), a prominent vector of human disease. Using field-capturedGff, we discovered thatSpiroplasmainfection induces changes of sex-biased gene expression in reproductive tissues that may be critical for tsetse’s reproductive fitness. Using aGfflab line composed of individuals heterogeneously infected withSpiroplasma, we observed that the bacterium and tsetse host compete for finite nutrients, which negatively impact female fecundity by increasing the length of intrauterine larval development. Additionally, we found that when males are infected withSpiroplasma, the motility of their sperm is compromised following transfer to the female spermatheca. As such,Spiroplasmainfections appear to adversely impact male reproductive fitness by decreasing the competitiveness of their sperm. Finally, we determined that the bacterium is maternally transmitted to intrauterine larva at a high frequency, while paternal transmission was also noted in a small number of matings. Taken together, our findings indicate thatSpiroplasmaexerts a negative impact on tsetse fecundity, an outcome that could be exploited for reducing tsetse population size and thus disease transmission.
Noncytotoxic functions of killer cell granzymes in viral infections
Authors: de Jong Lisanne C. , Crnko Sandra , ten Broeke Toine , Bovenschen Niels
Published: September 2021

Cytotoxic lymphocytes produce granules armed with a set of 5 serine proteases (granzymes (Gzms)), which, together with the pore-forming protein (perforin), serve as a major defense against viral infections in humans. This granule-exocytosis pathway subsumes a well-established mechanism in which target cell death is induced upon perforin-mediated entry of Gzms and subsequent activation of various (apoptosis) pathways. In the past decade, however, a growing body of evidence demonstrated that Gzms also inhibit viral replication and potential reactivation in cell death–independent manners. For example, Gzms can induce proteolysis of viral or host cell proteins necessary for the viral entry, release, or intracellular trafficking, as well as augment pro-inflammatory antiviral cytokine response. In this review, we summarize current evidence for the noncytotoxic mechanisms and roles by which killer cells can use Gzms to combat viral infections, and we discuss the potential thereof for the development of novel therapies.
Commensal bacteria augment Staphylococcus aureus infection by inactivation of phagocyte-derived reactive oxygen species
Authors: Gibson Josie F. , Pidwill Grace R. , Carnell Oliver T. , Surewaard Bas G. J. , Shamarina Daria , Sutton Joshua A. F. , Jeffery Charlotte , Derré-Bobillot Aurélie , Archambaud Cristel , Siggins Matthew K. , Pollitt Eric J. G. , Johnston Simon A. , Serror Pascale , Sriskandan Shiranee , Renshaw Stephen A. , Foster Simon J.
Published: September 2021

Staphylococcus aureus is a human commensal organism and opportunist pathogen, causing potentially fatal disease. The presence of non-pathogenic microflora or their components, at the point of infection, dramatically increases S. aureus pathogenicity, a process termed augmentation. Augmentation is associated with macrophage interaction but by a hitherto unknown mechanism. Here, we demonstrate a breadth of cross-kingdom microorganisms can augment S. aureus disease and that pathogenesis of Enterococcus faecalis can also be augmented. Co-administration of augmenting material also forms an efficacious vaccine model for S. aureus. In vitro, augmenting material protects S. aureus directly from reactive oxygen species (ROS), which correlates with in vivo studies where augmentation restores full virulence to the ROS-susceptible, attenuated mutant katA ahpC. At the cellular level, augmentation increases bacterial survival within macrophages via amelioration of ROS, leading to proliferation and escape. We have defined the molecular basis for augmentation that represents an important aspect of the initiation of infection.
Photoromance, she read: Fandom and the politics of Italian media
Authors: Bonifazio Paola
Published: September 2021

This article examines Italian non-fiction media productions of the late 1950s and 1960s that represent the photoromance industry and its female fans. I argue that state-controlled and/or privately owned media outlets and their contributors (among them, Cesare Zavattini and Mario Soldati) scapegoated photoromances in defence of moral, social and cultural respectability, but also on the basis of anxieties towards the increasing role played by female audiences in the making of culture. Furthermore, I show that politically engaged documentaries similarly chastised the photoromance industry without necessarily serving the cause of women’s emancipation. Blaming photoromances for the degeneration of Catholic values, for the debasement of working-class culture and for the degradation of consumerist society, all films serve the same purpose of maintaining a patriarchal society’s status quo, of diverging attention from ‘higher’ cultural products and their exploitation of women’s bodies and of minimizing the important role that female fans played in the success of a global market.
Trailers as mediatized performances: Investigating the use of promotional videos among Italian contemporary theatre artists
Authors: Brilli Stefano , Gemini Laura
Published: September 2021

In the theatre sector, many companies, festivals and theatres have integrated promotional videos into their communication strategies. This recent development is undoubtedly due to the rise of social media and the increasing accessibility of video technologies, but also to the need for theatre companies to publicize their work in a media that combines creative autonomy with economic efficiency. Despite this widespread use, trailers in the performing arts have received little attention in academic literature. This article offers the first, exploratory study on the use of promotional videos in the field of contemporary theatre in Italy and on the connections between the current creation of digital promotional clips and the heritage of the Italian video-theatre. Through in-depth interviews with sixteen of the leading Italian companies, this research aims to bring out the role theatre trailers play for performance artists.
The Photoromance: A Feminist Reading of Popular Culture, Paola Bonifazio (2020)1
Authors: Buonanno Milly
Published: September 2021

Review of: The Photoromance: A Feminist Reading of Popular Culture, Paola Bonifazio (2020)

Cambridge: MIT Press, 248 pp.,

ISBN 978-0-26253-923-9, p/bk, $29.95
Viaggio sulla luna: Voyage dans la Lune (Georges Méliès, 1902), Antonio Costa (2013)
Cabiria: (Giovanni Pastrone, 1914). Lo spettacolo della Storia, Silvio Alovisio (2014)
Ma l’amor mio non muore! (Mario Camerini, 1913): La diva e l’arte di comporre lo spazio, Stella Dagna (2014)
La presa di Roma - 20 Settembre 1870 (Filoteo Alberini, 1905): La nascita di una nazione, Giovanni Lasi (2015)
I topi grigi: (Emilio Ghione, 1918) Il romanzo cinematografico di Za la Mort, Denis Lotti (2018)
Authors: Bertellini Giorgio
Published: September 2021

Review of: Viaggio sulla luna: Voyage dans la Lune (Georges Méliès, 1902), Antonio Costa (2013)

Milan: Mimesis, 120 pp.,

ISBN 978-8-85751-624-0, p/bk, €10.00

 

Cabiria: (Giovanni Pastrone, 1914). Lo spettacolo della Storia, Silvio Alovisio (2014)

Milan: Mimesis, 114 pp.,

ISBN 978-8-85752-157-2, p/bk, €8.00

 

Ma l’amor mio non muore! (Mario Camerini, 1913): La diva e l’arte di comporre lo spazio, Stella Dagna (2014)

Milan: Mimesis, 96 pp.,

ISBN 978-8-85752-296-8, p/bk, €8.00

 

La presa di Roma - 20 Settembre 1870 (Filoteo Alberini, 1905): La nascita di una nazione, Giovanni Lasi (2015)

Milan: Mimesis, 108 pp.,

ISBN: 978-8-85753-048-2, p/bk, €9.00

 

I topi grigi: (Emilio Ghione, 1918) Il romanzo cinematografico di Za la Mort, Denis Lotti (2018)

Milan: Mimesis, 98 pp.,

ISBN 978-8-85755-214-9, p/bk, €9.00
Truth as a Victim: The challenge of anti-trafficking education in the age of Q
Authors: Benton Bond , Peterka-Benton Daniela
Published: September 2021

The QAnon conspiracy threatens anti-trafficking education because of its broad dissemination and focus on a range of myths about trafficking. These myths are rooted in historic and ongoing misinformation about abductions, exploitation, and community threats. This article examines the extent of QAnon’s co-optation of human trafficking discourses and evaluates its connection to trafficking myths, particularly related to gender, race, class, and agency. From this perspective, the article considers how anti-trafficking education can respond to these myths and build a pedagogy in the age of Q.
Fuerzas externas y agencia individual en el Medievo Nórdico: los vicios humanos y las actitudes honorables como herramientas del destino
Authors: Martín Páez Mario
Published: September 2021

El objetivo de este artículo es analizar las formas en las que el destino toma presencia en el Medievo Nórdico. Nos centraremos especialmente en V?lsunga saga y su contexto de producción. Veremos que las dinámicas sociales de Islandia y Noruega durante el siglo XIII condicionan la representación del destino y los efectos que tiene sobre el individuo. La necesidad de la reciprocidad era crucial para el mantenimiento de una sociedad basada en las relaciones personales y en sistemas de amistad. Por ello, la avaricia es uno de los principales elementos transgresores condenados en esta saga. En dicha narrativa, un tesoro maldito atrae la codicia de los personajes y los motivará a transgredir otras normas fundamentales. Esta maldición fija a la vez un destino fatídico que pone en cuestión la libertad que un individuo puede tener en un mundo condicionado. Estos determinantes son impuestos también por otras fuerzas externas que encuentran su comparación con el propio destino. Así, demostraremos que el honor y las exigencias impuestas dentro de una estructura de parentesco son representadas con la misma inexorabilidad que el destino y la misma destructividad que la codicia. Tanto el honor excesivo como la codicia tendrán la capacidad de arrastrar a los individuos a un futuro aciago que engullirá tanto a los cómplices como a los inocentes.
Inhibitory effects of fenbendazole, an anthelmintics, on lipopolysaccharide-activated mouse bone marrow cells
Authors: Park Seo-Ro , Joo Hong-Gu
Published: September 2021

Fenbendazole (FBZ) is a commonly used anthelmintic in veterinary medicine that has recently been found to have anticancer effects in humans. On the other hand, few studies have examined the anti-inflammatory effects of FBZ, and its mechanism is unknown. In this study, mouse bone marrow cells (BMs) were treated with lipopolysaccharide (LPS), a representative inflammation-inducing substance, to generate a situation similar to osteomyelitis in vitro. The effect of FBZ on inflammatory BMs was examined by measuring the metabolic activity, surface marker expression, cell nuclear morphology, and mitochondrial membrane potential (MMP) of BMs. FBZ decreased the metabolic activity and MMP of LPS-treated BMs. Annexin Ⅴ-fluorescein isothiocyanate/propidium iodide staining and Hoechst 33342 staining showed that FBZ reduced the number of viable cells and induced the cell death of inflammatory BMs. In addition, FBZ reduced the proportion of granulocytes more than B lymphocytes in LPS-treated BMs. Overall, FBZ induces cell death by destabilizing the MMP of LPS-induced inflammatory BMs. FBZ can play a role as an anthelmintic and anticancer agent and an anti-inflammatory agent.
Genome-wide polygenic analysis of multiple sclerosis markers
Authors: Timasheva Ya. R. , Nasibullin T. R. , Tuktarova I. A. , Erdman V. V. , Galiullin T. R. , Zaplakhova O. V. , Bakhtiiarova K. Z.
Published: September 2021

Objective: to perform a genome-wide polygenic analysis of multiple sclerosis (MS) markers in the ethnic groups of Bashkirs, Russians, and Tatars living in the Republic of Bashkortostan (Russian Federation).

Patients and methods. Genotyping was performed using allele-specific polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism analysis of genes of the human leukocyte differentiation antigens CD6 (rs17824933), CD40 (rs6074022), CD58 (rs2300747), CD86 (rs9282641), transcription factors SOX8 (rs2744148) and ZBTB46 (rs6062314), beta-mannosidase MANBA (rs228614), C-type lectin domain CLEC16A (rs12708716), ribosomal protein S6 kinase B1 RPS6KB1 (rs180515), and long noncoding RNA gene PVT1 (rs759648) in 644 patients with MS and 1408 controls. Multilocus analysis of the disease associations with combinations of genotypes and alleles of the studied polymorphic loci was performed using the APSampler algorithm.

Results and discussion. We determined the distribution of genotype and allele frequencies of the studied polymorphic loci in the ethnic groups of Bashkirs, Russians, and Tatars. We also observed disease associations with CD58 (rs2300747) and RPS6KB1 (rs180515) polymorphic loci in Russian men, CD86 (rs9282641) in Russian, PVT1 (rs759648) in Tatar women, CD40 (rs6074022) in Bashkir men, and identified 19 combinations of genotypes and/or alleles significantly associated with MS.

Conclusion. Based on the genome-wide polygenic analysis of MS markers, we identified ethno- and gender-specific combined markers of the disease susceptibility.
Mechanisms of brain protection against autoimmune inflammation
Authors: Volkov A. I. , Melnikov M. V. , Boyko A. N.
Published: September 2021

A significant number of unique antigens expressed in the brain can activate an adaptive immune response, increasing the risk of autoimmune inflammation in the central nervous system (CNS). As a result, a complex protection system exists in the CNS to prevent autoimmune reactions. In addition to the blood-brain- and blood-cerebrospinal fluid-barriers, we discuss complex systems of antigen drainage and circulation of antigen-presenting cells in the CNS. Moreover, the interaction of the CNS with the peripheral immune system typically occurs in specific areas (choroid plexuses, perivascular spaces, and brain meninges), and resident cells of the innate immune system (macrophages, microglia, astrocytes) have limited opportunities for antigen presentation and do not migrate to regional lymph nodes. There are signs of activation of adaptive immunity against CNS antigens in normal conditions, which, however, do not lead to autoimmune diseases. The review covers the mechanisms of maintaining natural immune self-tolerance in the CNS and their failure in autoimmune CNS pathology.
Influence of von Willebrand factor on common pathophysiological mechanisms of cerebrovascular diseases and multiple sclerosis
Authors: Koltsov I. A. , Martynov M. Yu. , Yasamanova A. N. , Shchukin I. A. , Fidler M. S. , Boyko A. N.
Published: September 2021

Endothelial dysfunction is a universal pathological mechanism underlying or contributing to the development/progression of many diseases, including cerebrovascular disease and multiple sclerosis. Von Willebrand factor is a multimeric glycoprotein synthesized by endothelial cells and megakaryocytes that participates in a range of physiological and pathological processes, including primary hemostasis and coagulation. It also regulates secretion and transport of a variety of molecules, exerts a proinflammatory effect, modulates angiogenesis and smooth muscle mitotic activity, influences atherogenesis. In this review, we discuss the synthesis, secretion, and regulation of the von Willebrand factor within the context of endothelial dysfunction and other common mechanisms that play a significant role in brain tissue damage in cerebrovascular diseases and multiple sclerosis.
An Islamic Spiritual Alternative to Addiction Treatment and Recovery
Authors: Bensaid Benaouda , Machouche Salah Ben Tahar , Tekke Mustafa
Published: September 2021

The Islamic spirituality permeating the practice of Muslim religious beliefs, values, and norms, is positioned to play a pivotal role in addiction prevention, treatment, rehabilitation therapy and recovery of Muslim addicts. This study seeks to explore potential interconnections between spirituality, addiction treatments, recovery, and the ways and means with which Islamic spirituality may assist addicts in coping with inner urges, relapse, and recovery. This study seeks to lay the groundwork for future theoretical and empirical research on spirituality and addiction, development of spirituality-based addiction programs, and the assessment of related current spiritual philosophies, methods, and strategies. This inquiry discusses spirituality as a source of meaning-making and purpose cultivation, self-discipline, motivation, support, reintegration, and related issues arising in these regards, and highlights the need for utilizing spirituality as a critical instrument in addiction treatment programs. Islamic spirituality however is neither – and should not be considered - a sole treatment scheme, nor does it appreciate absolute reliance on non-spiritual means of recovery in favor of positivistic empirical methods. [Spiritualitas Islam meresap ke pelbagai praktik keberagamaan, nilai dan norma, yang mana hal ini juga berperan penting pada pencegahan, pengobatan, terapi rehabilitasi dan pemulihan kecanduan pada umat muslim. Artikel ini mengeksplorasi potensi keterkaitan antara spiritualitas, penyembuhan kecanduan, pemulihan dan cara serta sarana spiritualitas Islam dalam membantu pecandu mengelola kondisi batin, ketika kambuh dan pemulihan. Studi ini berusaha meletakkan dasar bagi penelitian teoretis dan empiris dimasa depan tentang spiritualitas dan kecanduan, pengembangan program kecanduan berbasis spiritualitas, dan penilaian filosofi, metode, dan strategi spiritual terkait. Artikel ini membahas spiritualitas sebagai sumber pembentukan makna dan penggalian tujuan, disiplin diri, motivasi, dukungan, reintegrasi, dan isu-isu terkait yang timbul dalam hal ini, dan menyoroti kebutuhan untuk memanfaatkan spiritualitas sebagai instrumen penting dalam program perawatan kecanduan. Spiritualitas Islam bagaimanapun juga bukan–dan tidak boleh dianggap–satu-satunya skema pengobatan, tapi juga tidak tergantung mutlak pada sarana pemulihan non-spiritual yang mendukung metode empiris positivistik.]