bluuebunny/crossref_metadata_2025 huggingface dataset:
INSP-16. Focused ultrasound-mediated blood-brain barrier disruption for the treatment of pediatric high-grade glioma
Authors: van Vuurden Dannis , Ries Mario
Published: June 2022

Pediatric patients with high-grade glioma (HGG), such as glioblastoma (GBM) and H3K27M-altered diffuse midline glioma (DMG) suffer from a dismal prognosis and a poor quality of life. So far, no therapeutic strategy has resulted in significant long-term survival benefit for these patients. Drug therapies have largely failed due to inadequate drug delivery to the brain as a result of the blood-brain barrier, preventing most drugs from entering the brain. Intrinsic and acquired tumor heterogeneity, with drug-resistant tumor cell subpopulations add to the therapeutic failure. Furthermore, these tumors evade the immune system by creating a highly tumor-promoting and immunosuppressive tumor immune microenvironment, which is composed of microglia and tumor-associated macrophages. Recently, microbubble-assisted, focused ultrasound-mediated blood-brain barrier disruption (FUS-BBBD) has emerged as a promising and clinically available technology to circumvent part of these problems. FUS-BBBD allows improved delivery of therapeutics (chemotherapy, small molecules, monoclonal antibodies, immunotherapies) to the brain. The technology is emerging both in preclinical and clinical pediatric neuro-oncology research, with invasive and minimally invasive clinical FUS-BBBD systems available for early phase clinical trials. How the right drugs in the optimal combination can be delivered with the best timing (pharmacokinetics) via FUS-BBBD has yet to be ascertained and is subject of in vitro and in vivo drug studies. Combining FUS-BBBD with compounds targeting microglia and tumor-associated macrophages potentially reverts the ‘immuno-cold’ tumor immune micro-environment towards an ‘immuno-hot’ state and might enhance systemic immunotherapies such as immune checkpoint inhibitor and CAR-T cell approaches. Furthermore, recent preclinical research evidenced that FUS-BBBD is able to enhance liquid biopsies by increasing the concentration of circulating biomarkers in blood. It could therefore be used for longitudinal monitoring of site-specific chemoresistance development during therapy. This presentation will provide an overview on preclinical and clinical developments in the field of FUS-BBBD-enhanced drug delivery, immune modulation and liquid biopsies. International collaboration in (pre)clinical studies with FUS-BBBD is needed to bring the field forward.
Low-risk meningioma: Initial outcomes from NRG Oncology/RTOG 0539
Authors: Rogers C Leland , Pugh Stephanie L , Vogelbaum Michael A , Perry Arie , Ashby Lynn S , Modi Jignesh M , Alleman Anthony M , Barani Igor J , Braunstein Steve , Bovi Joseph A , de Groot John F , Whitton Anthony C , Lindhorst Scott M , Deb Nimisha , Shrieve Dennis C , Shu Hui-Kuo , Bloom Beatrice , Machtay Mitchell , Mishra Mark V , Robinson Clifford G , Won Minhee , Mehta Minesh P
Published: June 2022

Background

Three- and five-year progression-free survival (PFS) for low-risk meningioma managed with surgery and observation reportedly exceeds 90%. Herewith we summarize outcomes for low-risk meningioma patients enrolled on NRG/RTOG 0539.

Methods

This phase II trial allocated patients to one of three groups per World Health Organization grade, recurrence status, and resection extent. Low-risk patients had either gross total (GTR) or subtotal resection (STR) for a newly diagnosed grade 1 meningioma and were observed after surgery. The primary endpoint was 3-year PFS. Adverse events (AEs) were scored using Common Terminology Criteria for Adverse Events (CTCAE) version 3.

Results

Among 60 evaluable patients, the median follow-up was 9.1 years. The 3-, 5-, and 10-year rates were 91.4% (95% CI, 84.2 to 98.6), 89.4% (95% CI, 81.3 to 97.5), 85.0% (95% CI, 75.3 to 94.7) for PFS and 98.3% (95% CI, 94.9 to 100), 98.3%, (95% CI, 94.9 to 100), 93.8% (95% CI, 87.0 to 100) for overall survival (OS), respectively. With centrally confirmed GTR, 3/5/10y PFS and OS rates were 94.3/94.3/87.6% and 97.1/97.1/90.4%. With STR, 3/5/10y PFS rates were 83.1/72.7/72.7% and 10y OS 100%. Five patients reported one grade 3, four grade 2, and five grade 1 AEs. There were no grade 4 or 5 AEs.

Conclusions

These results prospectively validate high PFS and OS for low-risk meningioma managed surgically but raise questions regarding optimal management following STR, a subcohort that could potentially benefit from adjuvant therapy.
A CRISPR/Cas12a-empowered surface plasmon resonance platform for rapid and specific diagnosis of the Omicron variant of SARS-CoV-2
Authors: Chen Zhi , Li Jingfeng , Li Tianzhong , Fan Taojian , Meng Changle , Li Chaozhou , Kang Jianlong , Chai Luxiao , Hao Yabin , Tang Yuxuan , Al-Hartomy Omar A , Wageh Swelm , Al-Sehemi Abdullah G , Luo Zhiguang , Yu Jiangtian , Shao Yonghong , Li Defa , Feng Shuai , Liu William J , He Yaqing , Ma Xiaopeng , Xie Zhongjian , Zhang Han
Published: June 2022

The outbreak of the COVID-19 pandemic was partially due to the challenge of identifying asymptomatic and presymptomatic carriers of the virus, and thus highlights a strong motivation for diagnostics with high sensitivity that can be rapidly deployed. On the other hand, several concerning SARS-CoV-2 variants, including Omicron, are required to be identified as soon as the samples are identified as ‘positive’. Unfortunately, a traditional PCR test does not allow their specific identification. Herein, for the first time, we have developed MOPCS (Methodologies of Photonic CRISPR Sensing), which combines an optical sensing technology-surface plasmon resonance (SPR) with the ‘gene scissors’ clustered regularly interspaced short palindromic repeat (CRISPR) technique to achieve both high sensitivity and specificity when it comes to measurement of viral variants. MOPCS is a low-cost, CRISPR/Cas12a-system-empowered SPR gene-detecting platform that can analyze viral RNA, without the need for amplification, within 38 min from sample input to results output, and achieve a limit of detection of 15 fM. MOPCS achieves a highly sensitive analysis of SARS-CoV-2, and mutations appear in variants B.1.617.2 (Delta), B.1.1.529 (Omicron) and BA.1 (a subtype of Omicron). This platform was also used to analyze some recently collected patient samples from a local outbreak in China, identified by the Centers for Disease Control and Prevention. This innovative CRISPR-empowered SPR platform will further contribute to the fast, sensitive and accurate detection of target nucleic acid sequences with single-base mutations.
High within-clutch repeatability of eggshell phenotype in Barn Swallows despite less maculated last-laid eggs
Authors: Beech Ava-Rose F , Santos Mattheus C , Smith Emily B , Berejka Ben W , Liu Yujie , Tsunekage Toshi , Levin Iris I
Published: June 2022

Ecological and life-history variation and both interspecific and intraspecific brood parasitism contribute to diversity in egg phenotype within the same species. In this study, Barn Swallows (Hirundo rustica erythrogaster) laid eggs with high intraclutch repeatability in egg size, shape, and maculation. Despite this high intraclutch repeatability, last-laid eggs had consistently less of the eggshell covered in spots and fewer spots than earlier-laid eggs in the clutch. We examined sources of interclutch and intraclutch variation using both direct measurements and custom software (SpotEgg, NaturePatternMatch) that provide detailed information on egg characteristics, especially maculation measures. In addition to our main findings, maculation on different sides of the egg was highly repeatable; however, only shape, proportion of the eggshell maculated, and average spot size were repeatable between first and replacement clutches. Low intraclutch variation in maculation could allow females to recognize their clutch and this may be adaptive for colonial nesting species, such as the Barn Swallow. Characterizing intraspecific variation in egg size, shape, and maculation is the first step in understanding whether intraclutch variation is low enough—and interclutch variation high enough—such that eggs could serve as identity signals.
Neural Correlates of Smooth Pursuit Eye Movements in Schizotypy and Recent Onset Psychosis: A Multivariate Pattern Classification Approach
Authors: Schröder Rebekka , Faiola Eliana , Fernanda Urquijo Maria , Bey Katharina , Meyhöfer Inga , Steffens Maria , Kasparbauer Anna-Maria , Ruef Anne , Högenauer Hanna , Hurlemann René , Kambeitz Joseph , Philipsen Alexandra , Wagner Michael , Koutsouleris Nikolaos , Ettinger Ulrich
Published: June 2022

Schizotypy refers to a set of personality traits that bear resemblance, at subclinical level, to psychosis. Despite evidence of similarity at multiple levels of analysis, direct comparisons of schizotypy and clinical psychotic disorders are rare. Therefore, we used functional magnetic resonance imaging (fMRI) to examine the neural correlates and task-based functional connectivity (psychophysiological interactions; PPI) of smooth pursuit eye movements (SPEM) in patients with recent onset psychosis (ROP; n = 34), participants with high levels of negative (HNS; n = 46) or positive (HPS; n = 41) schizotypal traits, and low-schizotypy control participants (LS; n = 61) using machine-learning. Despite strong previous evidence that SPEM is a highly reliable marker of psychosis, patients and controls could not be significantly distinguished based on SPEM performance or blood oxygen level dependent (BOLD) signal during SPEM. Classification was, however, significant for the right frontal eye field (FEF) seed region in the PPI analyses but not for seed regions in other key areas of the SPEM network. Applying the right FEF classifier to the schizotypal samples yielded decision scores between the LS and ROP groups, suggesting similarities and dissimilarities of the HNS and HPS samples with the LS and ROP groups. The very small difference between groups is inconsistent with previous studies that showed significant differences between patients with ROP and controls in both SPEM performance and underlying neural mechanisms with large effect sizes. As the current study had sufficient power to detect such differences, other reasons are discussed.
Public attitude toward Covid‐19 vaccination: The influence of education, partisanship, biological literacy, and coronavirus understanding
Authors: Miller Jon D. , Ackerman Mark S. , Laspra Belén , Polino Carmelo , Huffaker Jordan S.
Published: June 2022

The Covid‐19 pandemic posed new issues about vaccination and contagious diseases that had not been the focus of public policy debate in the United States since the tuberculosis pandemic of the late 19th century and the early 20th century. Using a national address‐based probability sample of American adults in 2020 and a structural equation model, this analysis seeks to understand the role of education, age, gender, race, education, partisanship, religious fundamentalism, biological literacy, and understanding of the coronavirus to predict individual intention concerning taking the Covid‐19 vaccine. Given the substantial changes in the United States since the tuberculosis pandemic, it is important to understand the factors that drive acceptance and hesitancy about Covid‐19 vaccination. We find that education, biological literacy, and understanding of the coronavirus were strong positive predictors of willingness to be vaccinated and religious fundamentalism and conservative partisanship were strong negative predictors of intent to vaccinate. These results should be encouraging to the scientific community.
Efficacy of Inspiratory Muscle Training on Respiratory Muscle Strength in Hematopoietic Stem Cell Recipients: A Systematic Review and Meta-analysis
Authors: Sampaio Larissa Melo , Fuzari Helen Kerlen Bastos
Published: June 2022

Objective:

To investigate whether inspiratory muscle training improves respiratory muscle strength and function and reduces dyspnea and fatigue in hematopoietic stem cell recipients.

Design:

A systematic review and meta-analysis of randomized controlled trials.

Participants:

People with hematological neoplasms who underwent hematopoietic stem cell transplantation.

Intervention:

Inspiratory muscle training with POWER breath Plus, POWERbreathe, Classic, and Threshold devices, with a load of 40% of the maximum inspiratory pressure.

Outcome Measures:

The primary outcomes were maximal inspiratory pressure, maximal expiratory pressure, forced expiratory volume in the first second of expiration (FEV1), forced vital capacity (FVC), and the FEV1/FVC ratio. Secondary outcomes were dyspnea, fatigue, respiratory rate, peripheral O2 saturation, quality of life, and functional capacity.

Results:

The search identified 3 eligible studies with a sample of 108 participants. Maximal inspiratory pressure was higher in the intervention group in the 3 studies reviewed, with an average difference of −9.3 cm H2O, −31.94 cm H2O, and −16 cm H2O in relation to the control group after inspiratory muscle training. One study found an improvement in the distance covered in the 6-minute walk test (34.22 m) and in the distance covered in the modified incremental shuttle walking test (66.43 m) in the intervention group.

Limitation:

This systematic review includes only 3 randomized controlled clinical trials.

Conclusion:

Inspiratory muscle training is effective in increasing inspiratory muscle strength and functional capacity in bone marrow transplant recipients. However, its effects on fatigue and dyspnea remain uncertain.
Comparison of Ocular Biometric Parameters Between Hispanic and Non-Hispanic Ethnicities in White Adults Undergoing Cataract Surgery
Authors: Lam Brandon C. , Weiss Menachem , Jing Frank , Zhu Christopher , Johnson Daniel A. , Kheirkhah Ahmad
Published: June 2022

Objectives:

To compare ocular biometric parameters between Hispanic and non-Hispanic White adult patients undergoing cataract surgery.

Methods:

We included 433 adult patients undergoing surgery for senile cataract. Only patients with race and ethnicities of Hispanic and non-Hispanic White were included. The following parameters measured by the IOLMaster 700 were compared between Hispanic and non-Hispanic patients: mean keratometry, corneal astigmatism, anterior chamber depth (ACD), lens thickness, vitreous length, axial length, white-to-white diameter, and emmetropic intraocular lens power.

Results:

There were 219 Hispanic patients and 214 non-Hispanic patients with a mean age of 70.1±7.7 years (range, 50–88 years), and 66.7% were women. Although sex distribution was similar between the two groups, Hispanic patients had a lower age compared with non-Hispanic patients (69.3±8.3 vs. 70.9±6.9 years, P=0.02). In biometric values, ACD was significantly lower in Hispanic patients (3.07±0.40 mm) than in non-Hispanic patients (3.16±0.37 mm, P=0.01). Such statistically significant difference persisted after adjustment for age and sex (P=0.01). No other significant differences were found in other ocular parameters measured.

Conclusions:

Anterior chamber depth is significantly shorter in Hispanic patients compared with non-Hispanic patients. Such ethnic difference should be considered when performing cataract and corneal surgeries because this ethnic difference may be associated with a higher risk of corneal endothelial injury.
High Levels of Pretreatment HIV-1 Drug Resistance Mutations Among South African Women Who Acquired HIV During a Prospective Study
Authors: Beesham Ivana , Parikh Urvi M. , Mellors John W. , Joseph Davey Dvora L. , Heffron Renee , Palanee-Phillips Thesla , Bosman Shannon L. , Beksinska Mags , Smit Jennifer , Ahmed Khatija , Makkan Heeran , Selepe Pearl , Louw Cheryl , Kotze Philip , Hofmeyr G. Justus , Singata‐Madliki Mandisa , Rees Helen , Baeten Jared M. , Wallis Carole
Published: June 2022

Background:

Pretreatment HIV drug resistance (PDR) undermines individual treatment success and threatens the achievement of UNAIDS 95-95-95 targets. In many African countries, limited data are available on PDR as detection of recent HIV infection is uncommon and access to resistance testing is limited. We describe the prevalence of PDR among South African women with recent HIV infection from the Evidence for Contraceptive Options and HIV Outcomes (ECHO) Trial.

Methods:

HIV-uninfected, sexually active women, aged 18–35 years, and seeking contraception were enrolled in the ECHO Trial at sites in South Africa, from 2015 to 2018. HIV testing was done at trial entry and repeated quarterly. We tested stored plasma samples collected at HIV diagnosis from women who seroconverted during follow-up and had a viral load >1000 copies/mL for antiretroviral resistant mutations using a validated laboratory-developed population genotyping assay, which sequences the full protease and reverse transcriptase regions. Mutation profiles were determined using the Stanford Drug Resistance Database.

Results:

We sequenced 275 samples. The median age was 23 years, and majority (98.9%, n = 272) were infected with HIV-1 subtype C. The prevalence of surveillance drug resistance mutations (SDRMs) was 13.5% (n = 37). Nonnucleoside reverse transcriptase inhibitor (NNRTI) mutations were found in 12.4% of women (n = 34). Few women had NRTI (1.8%, n = 5) and protease inhibitor (1.1%, n = 3) mutations. Five women had multiple NRTI and NNRTI SDRMs.

Conclusions:

The high levels of PDR, particularly to NNRTIs, strongly support the recent change to the South African national HIV treatment guidelines to transition to a first-line drug regimen that excludes NNRTIs.
Ramipril Improves Endothelial Function and Increases the Number of Endothelial Progenitor Cells in Patients With Systemic Lupus Erythematosus
Authors: Oliveira Ana Cecília Diniz , Arismendi Maria Izabel , Machado Luiz Samuel Gomes , Sato Emilia Inoue
Published: June 2022

Background/Objectives

Endothelial dysfunction and reduced number of endothelial progenitor cells (EPCs) in peripheral blood are contributing factors to cardiovascular disease in systemic lupus erythematosus (SLE) patients. Endothelial progenitor cell proliferation is regulated by vascular endothelial growth factor (VEGF). Angiotensin-converting enzyme inhibitors reduce cardiovascular mortality in patients with coronary heart disease.

Methods

This was a randomized trial including 37 female SLE patients without cardiovascular risk factors allocated into 2 groups: 19 patients received ramipril 10 mg/d for 12 weeks (IG) and 18 patients maintained without ramipril (CG). Endothelial function was assessed by brachial artery ultrasound measuring flow-mediated dilation, and EPCs were quantified by flow cytometry and cell culture, at baseline and after 12 weeks. Serum VEGF levels were measured by enzyme-linked immunosorbent assay. Statistical analysis was intention to treat. p < 0.05 was considered significant.

Results

After 12 weeks, higher flow-mediated dilation (6.17% vs. 11.14%, p < 0.001) was observed in IG, without change in CG (5.37% vs. 5.02%, p = 0.630). Higher number of EPC colony-forming units was also observed in IG (21.3 ± 10.4 vs. 31.6 ± 8.5, p < 0.001), without difference in CG (p = 0.714). No difference was found in EPCs evaluated by flow cytometry. Vascular endothelial growth factor level increased after 12 weeks in IG (p = 0.048), with no difference in CG (p = 0.661).

Conclusion

Ramipril improved endothelial function and increased the numbers of EPCs evaluated by cell culture and VEGF levels in SLE patients without cardiovascular risk factors. These data suggest that angiotensin-converting enzyme inhibitor bring an extra benefit beyond the hypotensive action and should be considered as a preferred antihypertensive drug in SLE patients.
WAVES (Web-based tool for Analysis and Visualization of Environmental Samples) – a web application for visualization of wastewater pathogen sequencing results
Authors: Triska Petr , Amman Fabian , Endler Lukas , Bergthaler Andreas
Published: June 2022

Environmental monitoring of pathogens provides an accurate and timely source of information for public health authorities and policymakers. In the last two years, wastewater sequencing proved to be an effective way of detection and quantification of SARS-CoV-2 variants circulating in population. Wastewater sequencing produces substantial amounts of geographical and genomic data. Proper visualization of spatial and temporal patterns in this data is crucial for the assessment of the epidemiological situation and forecasting. Here, we present a web-based dashboard application for visualization and analysis of data obtained from sequencing of environmental samples. The dashboard provides multi-layered visualization of geographical and genomic data. It allows to display frequencies of detected pathogen variants as well as individual mutation frequencies. The features of WAVES for early tracking and detection of novel variants in the wastewater are demonstrated in an example of BA.1 variant and the signature Spike mutation S:E484A. WAVES dashboard is easily customized through the editable configuration file and can be used for different types of pathogens and environmental samples.

Availability

WAVES source code is freely available at https://github.com/ptriska/WavesDash under MIT license.
Androgen receptor inhibition induces metabolic reprogramming and increased reliance on oxidative mitochondrial metabolism in prostate cancer
Authors: Crowell Preston D. , Giafaglione Jenna M. , Jones Anthony E. , Nunley Nicholas M. , Hashimoto Takao , Delcourt Amelie M.L. , Petcherski Anton , Bernard Matthew J. , Huang Rong Rong , Low Jin-Yih , Matulionis Nedas , Guan Xiangnan , Navone Nora M. , Alumkal Joshi J. , Haffner Michael C. , Ye Huihui , Zoubeidi Amina , Christofk Heather R. , Shirihai Orian S. , Divakaruni Ajit S. , Goldstein Andrew S.
Published: June 2022

Prostate cancer cells that survive clinical androgen receptor (AR) blockade mediate disease progression and lethality. Reprogrammed metabolic signaling is one mechanism by which tumor cells can survive treatment. However, how AR inhibition reprograms metabolism, and whether altered metabolism can be exploited to eradicate cells that survive AR blockade, remains unclear. Here, we comprehensively characterized the effect of AR blockade on prostate cancer metabolism using transcriptomics, metabolomics, and bioenergetics approaches. AR inhibition maintains oxidative mitochondrial metabolism and reduces glycolytic signaling, through hexokinase II downregulation and decreased MYC activity. Robust elongation of mitochondria via reduced DRP1 activity supports cell fitness after AR blockade. In addition, AR inhibition enhances sensitivity to complex I inhibitors in several models, suggesting that AR blockade increases reliance on oxidative mitochondrial metabolism. Our study provides an enhanced understanding of how AR inhibition alters metabolic signaling and highlights the potential of therapies that target metabolic vulnerabilities in AR-inhibited cells.
ISCA2 inhibition decreases HIF and induces ferroptosis in clear cell renal carcinoma
Authors: Green Yangsook Song , dos Santos Maria C. Ferreira , Fuja Daniel , Reichert Ethan , Campos Alexandre R. , Cowman Sophie J. , Kohan Jessica , Tripp Sheryl R. , Leibold Elizabeth A. , Sirohi Deepika , Agarwal Neeraj , Liu Xiaohui , Koh Mei Yee
Published: June 2022

Clear cell renal cell carcinoma (ccRCC), the most common form of kidney cancer, is typically initiated by inactivation of the von Hippel Lindau (VHL) gene, which results in the constitutive activation of the hypoxia inducible factors, HIF-1α and HIF-2α. Using a high throughput screen, we identify novel compounds that decrease HIF-1/2α levels and induce ferroptosis by targeting Iron Sulfur Cluster Assembly 2 (ISCA2), a component of the late mitochondrial Iron Sulfur Cluster (L-ISC) assembly complex. ISCA2 inhibition either pharmacologically or using siRNA decreases HIF-2α protein levels by blocking iron-responsive element (IRE)-dependent translation, and at higher concentrations, also decreases HIF-1α translation through unknown mechanisms. ISCA2 inhibition also triggers the iron starvation response, resulting in iron/metals overload and death via ferroptosis. ISCA2 levels are decreased in ccRCC compared to normal kidney, and decreased ISCA2 levels are associated with pVHL loss and with sensitivity to ISCA2 inhibition. Strikingly, pharmacological inhibition of ISCA2 using an orally available ISCA2 inhibitor significantly reduced ccRCC xenograft growth in vivo, decreased HIF-α levels and increased lipid peroxidation, suggesting increased ferroptosis in vivo. Thus, the targeting of ISCA2 may be a promising therapeutic strategy to inhibit HIF-1/2α and to induce ferroptosis in pVHL deficient cells.
The ER protein translocation channel subunit Sbh1 controls virulence ofCryptococcus neoformans
Authors: Santiago-Tirado Felipe H. , Hurtaux Thomas , Geddes-McAlister Jennifer , Nguyen Duy , Helms Volkhard , Doering Tamara L. , Römisch Karin
Published: June 2022

The fungal pathogenCryptococcus neoformansis distinguished by a cell wall-anchored polysaccharide capsule that is critical for virulence. Biogenesis of both cell wall and capsule relies on the secretory pathway. Protein secretion begins with polypeptide translocation across the endoplasmic reticulum (ER) membrane through a highly conserved channel formed by three proteins: Sec61, Sbh1, and Sss1. Sbh1, the most divergent, contains multiple phosphorylation sites, which may allow it to regulate entry into the secretory pathway in a species- and protein-specific manner. Absence ofSBH1causes a cell-wall defect in bothSaccharomyces cerevisiaeandC. neoformans, although other phenotypes differ. Notably, proteomic analysis showed that when cryptococci are grown in conditions that mimic aspects of the mammalian host environment (tissue culture medium, 37 °C, 5% CO2), a set of secretory and transmembrane proteins is upregulated in wild-type, but not inΔsbh1mutant cells. The Sbh1-dependent proteins show specific features of their ER targeting sequences that likely cause them to transit less efficiently into the secretory pathway. Many also act in cell-wall biogenesis, while several are known virulence factors; consistent with these observations, theC. neoformans Δsbh1mutant is avirulent in a mouse infection model. We conclude that, in the context of conditions encountered during infection, Sbh1 controls the entry of virulence factors into the secretory pathway ofC. neoformans, and thereby regulates fungal pathogenicity.

Importance

Cryptococcus neoformansis a yeast that causes almost 200,000 deaths worldwide each year, mainly of immunocompromised individuals. The surface structures of this pathogen, a protective cell wall surrounded by a polysaccharide capsule, are made and maintained by proteins that are synthesized inside the cell and travel outwards through the secretory pathway. A protein called Sbh1 is part of the machinery that determines which polypeptides enter this export pathway. We found that when Sbh1 is absent, bothC. neoformansand the model yeastS. cerevisiaeshow cell wall defects. Lack of Sbh1 also changes the pattern of secretion of both transmembrane and soluble proteins, in a manner that depends on characteristics of their sequences. Notably, multiple proteins that are normally upregulated in conditions similar to those encountered during infection, including several needed for cryptococcal virulence, are no longer increased. Sbh1 thereby regulates the ability of this important pathogen to cause disease.
3D (x-y-t) Raman imaging of tomato fruit cuticle: microchemistry during development
Authors: González Moreno Ana , Domínguez Eva , Mayer Konrad , Xiao Nannan , Bock Peter , Heredia Antonio , Gierlinger Notburga
Published: June 2022

The cuticle of tomato fruits was studied in-situ using Confocal Raman Microscopy. Microsections from cuticles isolated at different developmental stages were scanned to reveal the distribution of cuticle components with a spatial resolution of 342 nm by univariate and multivariate data analysis. From the three main components, cutin, polysaccharides and aromatics, the latter one exhibit the strongest Raman scattering intensity. Therefore, Raman imaging opened the view on phenolic acids and flavonoids within the cuticle and resulted in three schematic cuticle models depicting development.

At the earliest stage of development, which corresponded to the procuticle layer, phenolic acids were found across the entire cuticle. Based on a mixture analysis with reference component spectra, the phenolic acids were identified as mainly esterified p-coumaric acid together with free p-hydroxybenzoic acid. Later in development, during the cell expansion period of growth, phenolic acids accumulated in an outermost layer of the cuticle and in the middle region of the pegs. In these stages of development cellulose and pectin were appeared towards the epidermal layer, where later during ripening the flavonoid impregnation started. In the first ripening stage chalconaringenin was observed, while methoxylated chalcones were chosen by the algorithm to fit the mature cuticle spectra. The co-location with carbohydrates and esterified p-coumaric acid and methoxylated chalconaringenin suggest that they link polysaccharide and cutin domains. Within the cutin matrix, aromatics confer mechanical and thermal functions, while the outermost phenolic acid layer displays UV-B protection of the plant tissue.

One-sentence summary

New insights into the distribution of cutin, carbohydrates and phenolics along cross sections of green and mature tomato fruit cuticles by Raman mapping and multivariate data analysis.
Interactions in CSF1-driven Tenosynovial Giant Cell Tumors
Authors: van IJzendoorn David G.P. , Matusiak Magdalena , Charville Gregory W. , Spierenburg Geert , Varma Sushama , Colburg Deana R.C. , van de Sande Michiel A.J. , van Langevelde Kirsten , Mohler David G. , Ganjoo Kristen N. , Bui Nam Q. , Avedian Raffi S. , Bovée Judith V.M.G. , Steffner Robert , West Robert B. , van de Rijn Matt
Published: June 2022

The majority of cells in Tenosynovial Giant Cell Tumor (TGCT) are macrophages responding to CSF1 that is overproduced by a small number of neoplastic cells with a chromosomal translocation involving the CSF1 gene. Treatment with inhibitors of the CSF1 pathway has been clinically effective. An autocrine loop was postulated where the neoplastic cells are stimulated through the CSF1 receptor (CSF1R) expressed on their surface. Here we show that the neoplastic cells themselves do not express CSF1R and therefore may be unaffected by current therapies. We identified a new marker for synoviocytes, GFPT2, that highlights the tumor cells in TCGT and is associated with activation of the YAP1/TAZ pathway. The neoplastic cells in TGCT are highly similar non-neoplastic synoviocytes. Finally, we provide molecular support for the osteoclast-like features of the giant cells in TGCT that correlate with the destructive effects of TGCT on bone.
Validation of a Deep Learning Model to aid in COVID-19 Detection from Digital Chest Radiographs
Authors: Ajmera Pranav , Kharat Amit , Khaladkar Sanjay , Gupte Tanveer , Pant Richa , Kulkarni Viraj , Duddalwar Vinay , Patkar Deepak , Bhatia Mona , Lamghare Purnachandra
Published: June 2022

Introduction

Using artificial intelligence in imaging practice helps ensure study list reprioritization, prompt attention to urgent studies, and reduces the reporting turn-around time.

Purpose

We tested a deep learning-based artificial intelligence model that can detect COVID-19 pneumonia patterns from digital chest radiographs.

Material and Methods

The deep learning model was built using the enhanced U-Net architecture with Spatial Attention Gate and Xception Encoder. The model was named DxCOVID and was tested on an external clinical dataset. The dataset included 2247 chest radiographs comprising CXRs from 1046 COVID-19 positive patients (positive on RT-PCR) and 1201 COVID-19 negative patients.

Results

We compared the performance of the model with three different radiologists by adjusting the model’s sensitivity as per the individual radiologist. The area under the curve (AUC) on the receiver operating characteristic (ROC) of the model was 0.87 [95% CI: 0.85, 0.89].

Conclusion

When compared to the performance of three expert readers, DxCOVID matched the output of two of the three readers. Disease-specific deep learning models using current technology are mature enough to match radiologists’ performance and can be a suitable tool to be incorporated into imaging workflows.
Resisting accounting in the name of discipline
Authors: Perray-Redslob Ludivine , Morales Jeremy
Published: June 2022

Purpose

This paper examines micro-practices of resistance to understand how they influence accounting.

Design/methodology/approach

A qualitative methodology based on interviews is used to explore an extreme case of disciplinary organization, that of the French Armed Forces whereby secrecy and discipline are the norm. The study draws on James Scott's concept of infrapolitics to illustrate how service members manage to appear obedient and disciplined, while simultaneously criticizing and resisting accounting practices “below the radar” of surveillance.

Findings

The study describes “resistance in obedience” to account for how service members resist while following discipline. Three main forms of resistance are identified. Containment consists in obstructing and delaying a process of change that depends on willing participation of active supporters. Subversion consists in weakening the sources of information and the communication channels. Sabotage consists in fragmenting accounting (here a balanced scorecard) by separating performance indicators from cost accounting. The study shows that these three tactics of hidden and informal resistances prevent the spread of accounting reforms, disrupt transparency and create a blockade around financial information.

Research limitations/implications

The study of resistance to accounting in a setting where compliance and discipline are the norm shows how widespread it can be. In that respect, future research could provide a more systematic understanding of resistance in action and its conditions of possibility in various contexts and settings. This article further illustrates the allure of opacity against the threats of transparency and accountability. The use of accounting in opaque settings opens interesting avenues of research, since the appeal of accounting has often been related to the allure of transparency and to accounting's potential to create visibilities. Finally, this paper opens a perspective for future research on how micro-resistance meets micro-practices of power in the context of ostensibly liberated, participative and non-authoritarian management.

Originality/value

While previous literature argued that resistance to accounting arises when it is used to increase discipline, our findings challenge this assumed dichotomy, by showing that sometimes accounting is resisted in the name of discipline. This study further outlines the fact that the “allure” of transparency is not universal but can also prove disruptive and be contested. In addition, this study contributes to the literature on resistance to accounting that mainly focused on overt, dramatic and organized forms of resistances, by highlighting the existence of a more widespread, omnipresent yet hidden and mundane, day-to-day, form of opposition, which significantly influences accounting. Finally, the findings show that resistance is not only an outside force intersecting with accounting but also an intrinsic force that shapes accounting from the inside.
Omni micro-reseller's path-to-purchase and MSEs omnichannel readiness in the Indonesian affordable fashion industry
Authors: Maulana Amalia E. , Adisantoso Julio , Hartanto Bobie
Published: June 2022

Purpose

This study aims to present the path-to-purchase of omni micro-resellers in affordable fashion shopping centers and differentiates them from the existing knowledge of end-user’s purchase journey. Furthermore, the study aims to explore the omnichannel readiness for Micro and Small Enterprises (MSEs) merchants to provide a seamless experience for the micro-resellers.

Design/methodology/approach

This study adopted an ethnographic approach to gain deep insights into the unexplored omni journey of micro-resellers, using multiple techniques and respondent types in various locations.

Findings

Findings reveal that the journey of omni micro-reseller is not the same as the end-user's purchase journey. The new value needed in every path-to-purchase is an essential knowledge that helps MSE merchants in serving micro-resellers. MSE merchants' readiness is assessed by their ability to provide the best customer experience for their buyers, consisting of six omnichannel experience dimensions: researching, purchase-payment, shipping, omnichannel testing, return goods experience and relationship building.

Research limitations/implications

Using the Engel-Kollat-Blackwell (EKB) decision-making model, this study develops the path-to-purchase of omnichannel micro-resellers. The new readiness dimensions developed in this study are set as a potential measurement tool.

Practical implications

It provides new insights to benefit MSE merchants and the institutions responsible for enhancing merchant quality.

Originality/value

This study focuses on micro-resellers in the MSEs environment, the prominent buyers of affordable fashion in developing countries, which is a novelty of the study. Moreover, unlike previous studies that have focused on large and medium merchants, this study concentrates on MSE merchants. To the best of the authors’ knowledge, this study is one of the first studies to highlight ways to measure MSE merchants omnichannel readiness.
Global scenarios under crises: the case of post COVID-19 era
Authors: Hafezi Reza , Asemi Pardis
Published: June 2022

Purpose

COVID-19 pandemic has significantly influenced human society; statistics have shown many countries ended 2020 with minimal or even negative economic growth. This pandemic proved that development biased to economic issues without considering other factors such as social and environmental is not sustainable, and it can even be the source of the crisis. This paper aims to discover plausible alternative futures at the macrolevel where nations, businesses and societies can change routines, and approach to a better peaceful future.

Design/methodology/approach

To accomplish this, trends emerged after the COVID-19 pandemic are studied and some uncertainties are identified. At the intersections of uncertainties, scenarios are shaped based on the Global Business Network (GBN) methodology. GBN helps to draw macrolevel images about plausible futures. The main uncertainties rose from three different but interconnected natures including: approach to the globalization (social perspective), approach to the concept of value (business perspective) and approach to the governance (states/governance perspective). Each uncertainty can take two extreme alternatives; consequently, eight scenario spaces with different probability are formed by the intersection of alternatives. Then the most favorable scenario is introduced and strategies are proposed to achieve a better future.

Findings

In the current paradigm in which countries will sacrifice the environment for economic growth in the race to rapidly rebuild their economy, concerns for the post-COVID-19 will continue to mount. While, in the favorable scenario, value creation is sought in sustainable development. This means deviation from a favorable scenario to achieve short-term goals is completely predictable. Although we have learned that the COVID-19 pandemic is controllable and manageable as time goes by, but no effort or commitment has been seen in the governments to eradicate the COVID-19 sources (at least till today).

Originality/value

The main originality of this research appeared in the practical aspect. This paper analyzes and projects scenarios at the global level and studies challenges that societies, governments and businesses are facing in the modern world with biased development paradigms. Moreover, different viewpoints to deal with global crisis are assessed and criticized.
Mobile phone use among Ukrainian and US students: a library perspective
Authors: Hranchak Tetiana , Dease Nicholas , Lopatovska Irene
Published: June 2022

Purpose

This study aims to determine college/university students’ mobile phone practices to understand key user preferences and set a baseline understanding for the development of prospective library informational mobile services.

Design/methodology/approach

This study is based on the results of an online-survey method. The authors recruited students majoring in the Information Science program in School of Information at Pratt Institute (USA) (74 participants) and in Kyiv National University of Cultural and Arts (Ukraine) (89 participants).

Findings

The general trends in the use of mobile technologies by American and Ukrainian students were identified. Key components of library mobile services are offered. Such services may include information and reference service via messengers; development of library mobile applications of audio and video content; access to educational, scientific, popular science literature and fiction; and supplementing online services with library chatbots.

Research limitations/implications

This study was limited to only students majoring in information science at university; however, the data obtained helps outline several general trends common to student youth who are actively working with information.

Practical implications

The obtained results will be useful in the practical activities of libraries and other information institutions for the development of a comprehensive information service based on mobile technology.

Originality/value

This study contributes to understanding how to improve library informational service considering users habits and preferences. Libraries management and librarians can use the findings as a basis for prioritizing the improvement of library informational mobile service.
Improved reliability in planning large-scale infrastructure project delivery through Alliancing
Authors: Walker Derek H.T. , Vaz Serra Paulo , Love Peter E.D.
Published: June 2022

Purpose

Price reliability for complex and highly complicated infrastructure projects is problematic. Traditional project delivery approaches generally fail in achieving targeted end cost reliability. However, integrated project delivery (and particularly Alliancing), develop a far more reliable and robust project delivery plan and outturn time-cost targets. This paper aims to explore why this may be the case.

Design/methodology/approach

This case study investigated the project design, planning, cost/time estimation approach and how risk/uncertainty was dealt with. Five senior project delivery experts from an organisation that delivers multi-billion-dollar infrastructure projects in Australia were interviewed. These five experts collectively had 100+ cross-disciplinary experience years delivering complex infrastructure projects.

Findings

Alliancing adopts a radically different approach to project design, time/cost planning and risk assessment and management to traditional project delivery approaches. Key findings explain how the project alliance agreement designs-in processes that maximises team integration and collaboration. Analysis concludes that design thinking is used to craft and shape collaborative behaviours and project governance. Additionally, including project owner and facilities operator representatives in the project team adds valuable insights, expertise and knowledge contributing to planning reliability.

Research limitations/implications

This study is exploratory and focussed on complex infrastructure projects so findings cannot be generalised.

Practical implications

We unpack Alliancing processes that develop the target outturn cost plan, comprising a holistic and realistic plan to design a project to meet expected project outcomes. This case study may serve as an exemplar for complex project delivery.

Social implications

This paper illustrates how Alliancing more effectively delivers best value than traditional procurement approaches through its TOC-TAE processes.

Originality/value

The paper contributes to the scant existing academic literature analysing these processes. Its novel contribution is explaining how Alliancing treats unexpected events that in traditional delivery forms trigger expensive and time-energy-wasting disputation. This case study may serve as an exemplar for complex project delivery.
Authentic assessment targeting sustainability outcomes: a case study exploring student perceptions
Authors: Asgarova Rana , Macaskill Anne , Abrahamse Wokje
Published: June 2022

Purpose

The purpose of this study was to understand student experiences of authentically assessed community partnership projects and reflect on authentic assessment from a social and environmental sustainability perspective.

Design/methodology/approach

The authors present an elaborated case study including graduate-level courses at a university in Aotearoa, New Zealand. The authors draw on a thematic analysis of in-depth semi-structured interviews and written reflections from 18 students.

Findings

Students appreciated the benefits of authentic assessment, such as workplace realism, a greater level of personal investment and opportunities to draw on diverse skills. Teams varied in how they navigated novel challenges and in their ability to develop focused projects capable of affecting change for sustainability. Students considered group work the greatest obstacle to achieving sustainability goals.

Originality/value

The case study provides a novel contribution by exploring in-depth the student experience of authentic assessment activities designed to foster social and environmental sustainability outcomes. The authors provide practical limitations of authentic assessment and discuss tensions between authentic assessment and other education goals.