bluuebunny/crossref_metadata_2025 huggingface dataset:
Managing periprosthetic tibia fractures: International perspectives
Authors: Lewis Daniel P. , Tarrant Seth M. , MacKenzie Stuart , Cornford Lachlan , Sato Toru , Shiota Naofumi , Balogh Zsolt J.
Published: March 2023

Knee arthroplasty, both total knee and unicompartmental, has had a significant impact on millions of patients globally. Although satisfaction is usually high, complications such as periprosthetic fracture are increasingly common. Distal femur periprosthetic fractures are relatively well researched and understood in comparison with periprosthetic proximal tibia fractures (PTFs). The management of PTFs is essentially an evidence-free area. This review explores the literature (or lack thereof) and integrates cases from Australia and Japan. As it stands, there is scant literature relating to all facets of PTFs, including, most concerningly, the management of them. Larger studies are required to help further investigate this important interface between arthroplasty and orthopaedic trauma. As a guide, those with loose prostheses will likely benefit most from revision total knee arthroplasty, while those with well-fixed prostheses can be managad according to the fracture with homage paid to the presence of the prosthesis. The use of periarticular locked plates is likely a better option over conventional large or small fragment plates. Nonoperative management is a viable option for selected individuals and can be associated with favorable outcomes.
Exploring Delay to Follow-Up in a Rural Multidisciplinary Cleft Clinic
Authors: Byrnes Yasmeen M. , Miller Stephanie P. , Frank Katie , Hoffman Rebecca L. , Kauffman Christian A.
Published: March 2023

Background

Oral clefts require longitudinal multidisciplinary care with follow-up visits at regular intervals throughout a patient's childhood, and delayed care can be detrimental. Although loss to follow-up is commonly studied, this metric does not account for patients that do return to care, but months or years later than recommended. The aim of this study was to explore and determine risk factors for delay to follow-up (DTFU) in a cleft clinic at a rural academic center.

Methods

Medical records from the multidisciplinary cleft clinic at a single rural tertiary care institution between January 1, 2010, and December 31, 2019, were reviewed. The primary outcome was DTFU, measured as the difference in days between recommended and actual follow-up dates for a given visit.

Results

A cohort of 282 patients was analyzed, with a total of 953 visits. A total of 71% of patients experienced at least 1 delay in follow-up of 30 days or longer, and 50% had at least 1 delay of 90 days or longer. Out of all visits, the mean DTFU was 73 days (around 2.5 months). For 23% of patients, at least half their visits were delayed by more than 90 days, whereas 11% experienced a delay of more than 90 days with every visit. Patients who failed to show up to at least 1 appointment had significantly higher risk of DTFU (P < 0.0001). Driving distance, driving time, SES, stage of cleft care, and cleft phenotype were not correlated with DTFU. For canceled appointments, 50.5% of recorded cancellation reasons were patient driven.

Conclusions

Delay to follow-up in a multidisciplinary cleft clinic was prevalent in this rural cohort, with half of patients experiencing delays of 3 months or longer, and about 1 in 9 experiencing this delay with every visit. Delay to follow-up identifies patients with consistently high rates of delay in care, which could eventually lead to targeted interventions to increase compliance. Delay to follow-up may be a new and valuable measure of cleft care compliance that can be easily implemented by other institutions. Further investigation is needed to determine the relationship between delay and clinical outcomes in cleft patients.
Augmenting Breast Implant Research
Authors: Shih Sabrina , Salazar Hector F. , Poveromo Luke P. , Askinas Carly , Vernice Nicholas , Corpuz George S. , O'Connell Gillian M. , Dong Xue , Spector Jason
Published: March 2023

Background

Because of the association of textured breast implants with breast implant–associated anaplastic large cell lymphoma, anatomically shaped breast implants, which rely on a textured surface to maintain rotational stability, have been recalled from the market. The dearth of anatomically shaped implants on the market reflects a need for novel breast implant technology, which has been traditionally developed by commercial breast implant manufacturers due to the complexities of implant manufacturing. To increase the accessibility of preclinical breast implant research, miniature breast implants made from polydimethylsiloxane were designed and fabricated for high throughput and low-cost prototyping and in vivo testing of both smooth and textured implants in a laboratory setting.

Methods

Two-piece negative molds measuring 2 × 1 cm were constructed in Fusion360 and 3D printed in Polysmooth filament. Textured molds were painted with a mixture of an epoxy and fine sugar or granular salt to create textured surfaces, while molds for smooth implants were smoothed using ethanol spray. Molds were injected with polydimethylsiloxane and cured for 12 hours at 37°C. The surface topography of laboratory-made implants and commercial textured and smooth implant shells was analyzed using scanning electron microscopy and implants were evaluated in vivo in an immunocompetent rodent model.

Results

Implants retained the original dome shape of the 3D-printed molds. Qualitative assessment of scanning electron microscopy images demonstrated similar surface topography between laboratory-made and commercial smooth and textured implants. There was no statistical difference in the diameter or density of the surface indentations of the Allergan's textured implant compared with laboratory-made textured implants (P > 0.05). Finally, the surface topography and thickness of laboratory-made implant capsules were similar to previously published data using industry made miniature silicone devices implanted in rats.

Conclusions

This study demonstrates a low-cost, highly customizable approach to fabricate miniature smooth and textured breast implant prototypes for in vivo studies. The accessibility of this implant fabrication strategy allows nonindustry investigators to develop novel implant designs more rapidly for preclinical investigation.
A Critical Analysis of Factors Associated With Anteroposterior Implant Flipping in Immediate Breast Reconstruction
Authors: Leibl Kayla E. , Hwang Lyahn K. , Anderson Cassidy , Weichman Katie E.
Published: March 2023

Background

Implant-based reconstruction remains the most common form of postmastectomy breast reconstruction. With ever-evolving device characteristics, including the advent of high-profile, cohesive, fifth-generation implants, the incidence of anterior-posterior flipping of implants is presenting a new challenge. Patient and device characteristics associated with this phenomenon have yet to be fully elucidated.

Methods

Patients who underwent nipple- or skin-sparing mastectomy with subsequent 2-stage or direct-to-implant reconstruction with smooth implants between 2015 and 2021 were retrospectively identified and stratified by incidence of implant flipping. Patient, procedural, and device characteristics were evaluated.

Results

Within 165 patients (255 reconstructed breasts), 14 cases of implant flipping were identified (flip rate 5.5%). All flips occurred in patients with cohesive implants (odds ratio [OR], 87.0; P = 0.002). On univariate analysis, extra full implant profile (OR, 11.2; P < 0.001) and use of a smooth tissue expander for 2-stage reconstruction (OR, 4.1; P = 0.03) were associated with flipping. Implants that flipped were larger than those that did not (652.5 ± 117.8 vs 540.1 ± 171.0 mL, P = 0.0004). Prepectoral implant placement (OR, 2.7; P = 0.08) and direct-to-implant method (OR, 3.17; P = 0.07) trended toward association, but this effect was not significant. Patient BMI, weight fluctuation during the reconstructive course, mastectomy weight, AlloDerm use, and history of seroma or periprosthetic infection were not associated with flipping.

Conclusion

Patients who receive a highly cohesive, high profile, larger implant are at increased risk for implant flipping. In addition, patients who receive a smooth tissue expander are more likely to experience flipping of their subsequent implant, compared with those who had textured tissue expanders. These characteristics warrant consideration during device selection to minimize discomfort, aesthetic deformity, and the need for reoperation.
Short chain fatty acids: key regulators of the local and systemic immune response in inflammatory diseases and infections
Authors: Ney Lisa-Marie , Wipplinger Maximilian , Grossmann Martha , Engert Nicole , Wegner Valentin D. , Mosig Alexander S.
Published: March 2023

The human intestinal microbiome substantially affects human health and resistance to infections in its dynamic composition and varying release of microbial-derived metabolites. Short-chain fatty acids (SCFA) produced by commensal bacteria through fermentation of indigestible fibres are considered key regulators in orchestrating the host immune response to microbial colonization by regulating phagocytosis, chemokine and central signalling pathways of cell growth and apoptosis, thereby shaping the composition and functionality of the intestinal epithelial barrier. Although research of the last decades provided valuable insight into the pleiotropic functions of SCFAs and their capability to maintain human health, mechanistic details on how SCFAs act across different cell types and other organs are not fully understood. In this review, we provide an overview of the various functions of SCFAs in regulating cellular metabolism, emphasizing the orchestration of the immune response along the gut–brain, the gut–lung and the gut–liver axes. We discuss their potential pharmacological use in inflammatory diseases and infections and highlight new options of relevant human three-dimensional organ models to investigate and validate their biological functions in more detail.
Clinical outcomes after extended 12-month antiretroviral therapy prescriptions in a community-based differentiated HIV service delivery programme in South Africa: a retrospective cohort study
Authors: Lewis Lara , Sookrajh Yukteshwar , van der Molen Johan , Khubone Thokozani , Sosibo Phelelani , Maraj Munthra , van Heerden Rose , Little Francesca , Kassanjee Reshma , Garrett Nigel , Dorward Jienchi
Published: March 2023

Introduction

There is an urgent need for more efficient models of differentiated antiretroviral therapy (ART) delivery for people living with HIV (PLHIV), with the World Health Organization calling for evidence to guide whether annual ART prescriptions and consultations (12M scripts) should be recommended in global guidelines. We assessed the association between 12M scripts (allowed temporarily during the COVID-19 pandemic) versus standard 6-month prescriptions and clinical review (6M scripts) and clinical outcomes.

Methods

We performed a retrospective cohort study using routine, de-identified data from 59 public clinics in KwaZulu-Natal, South Africa. We included PLHIV aged>18 years with a recent suppressed viral load (VL) who had been referred for community ART delivery with 6M or 12M scripts. We used modified Poisson regression to compare 12-month retention-in-care (not >90 days late for any visit) and viral suppression (<50 copies/mL) between prescription groups.

Results

Among 27,148 PLHIV referred for community ART between Jun-Dec 2020, 42.6% received 6M scripts and 57.4% 12M scripts. The median age was 39 years (interquartile range [IQR] 33-46) and 69.4% were women. Age, gender, prior community ART use and time on ART were similar in the two groups. However, more of the 12M script group had a dolutegravir-based regimen (60.0% versus 46.3%). The median (IQR) number of clinic visits in the 12 months of follow-up was 1(1-1) in the 12M group and 2(2-3) in the 6M group. Retention at 12 months was 94.6% (95% confidence interval [CI] 94.2%-94.9%) among those receiving 12M scripts and 91.8% (95% CI 91.3%-92.3%) among those with 6M scripts. 17.1% and 16.9% of clients in the 12M and 6M groups were missing follow-up VL data, respectively. Among those with VLs, 91.0% (95% CI 90.5%-91.5%) in the 12M group and 89.7% (95% CI 89.0%-90.3%) in the 6M group were suppressed. After adjusting for age, gender, ART regimen, time on ART, prior community ART use and calendar month, retention (adjusted risk ratio [aRR]: 1.03, 95% CI 1.01-1.05) and suppression (aRR: 1.01, 95% CI 1.00-1.02) were similar in the prescription groups.

Conclusions

Wider use of 12M scripts could reduce clinic visits without impacting short-term clinical outcomes.
Complications Post Endovascular Abdominal Aortic Aneurysm Repair in Patients with Diabetes Mellitus: A Meta-analysis and Systematic Review
Authors: Otify EA , Mekki M , Borucki J , Dhatariya K , Stather P W
Published: March 2023

Background

People with diabetes mellitus (DM) have higher long-term mortality following abdominal aortic aneurysm (AAA) repair than those without DM. However, whether this adverse outcome is directly related to their aneurysm is unclear.

Aims

To determine the rates of complications in people with and without DM post endovascular abdominal aortic aneurysm repair. Primary outcome data include AAA sac enlargement, reinterventions, endoleaks, post-operative AAA rupture and conversion to open surgical repair.

Methods

PubMed, Embase and Cochrane databases were searched for primary research studies between 2005 and 2023 according to PRISMA guidelines. Those undergoing AAA repair via endovascular aneurysm repair were included.

Results

Thirty-five studies were identified totalling 90,347 people in the control group, and 17,660 in the DM group. Those with DM had a lower rate of reintervention compared to controls (9.94% v 11.58%; OR 0.89, 95% CI [0.82-0.97]; P=0.005), however there was no significant difference in the rate of overall, type I or type II endoleaks (P=0.22, P=0.29, P=0.15 respectively).

People with DM were also less likely to have sac enlargement post AAA repair (9.66% v 11.27%; OR 0.79, 95% CI [0.68-0.93]; P=0.003). Additionally, people with DM had a significantly reduced rate of conversion to open surgery (2.11 % DM v 3.12% control; OR 0.80, CI [0.66-0.97]: P=0.02).

Conclusion

Reinterventions, sac enlargement post AAA repair, and conversion to open surgical repair were significantly lower in people with DM, however the cause for these differences remains unclear.
In-silico Screening ofOriganum vulgarePhytocompounds as Potential Drug Agents AgainstVp35Protein of the Ebola Virus
Authors: Saeed Malaika , Ashraf Aqeela , Sabir Burhan , Zafar Muhammad Osama , Raza Muhammad Hassan , Saif Rashid
Published: March 2023

The leading cause of the Ebola virus outbreak during 2013-16 in Western Africa was a lack of targeted anti- viral drug choices, a fast rate of mutations and the unavailability of many of the structural proteins and annotations within its genome. The surroundings of the Ebola River in DR-Congo fail to get rid of this endemic, the reason behind this was believed to be its origin from non-human primates, which made its risk assessment and tracing difficult. The Vp35 is a multifunctional protein with innate immune antagonistic properties and is considered one of the most suitable drug targets within this virus. The main motive of this study is to discover a potential anti-viral drug against the Ebola virus by targeting the aforementioned protein with different phytocompounds of oregano that have the lowest binding energies and qualifies over different simulation parameters, so firstly, molecular docking was performed on its 28 compounds using PyRx to get the best complexes with minimum binding energies e.g., -8.9Kcal/mol. Ligands with the best docking scores were gone through Lipinski’s rule of five for drug likeliness potential. For the drug affirmation, molecular dynamic simulation was also performed with the best two docked complexes using NAMD/VMD to find out their conformational stability through RMSD, RMSF, Rg, SASA and H-bond analyses. Current computer-generated prediction suggested that Ursolic acid and Oleanolic acid possess potential inhibitory effects against virus replication. Furthermore, paradigm shifts of usage of natural and herbal products for treating infectious diseases are being encouraged here, However, further wet-lab experiments and clinical trials are still needed to determine the robustness of these virtually tested phytocompounds against the Vp35 protein of the Ebola virus.
Generalizable neuromarker for autism spectrum disorder across imaging sites and developmental stages: A multi-site study
Authors: Itahashi Takashi , Yamashita Ayumu , Takahara Yuji , Yahata Noriaki , Aoki Yuta Y. , Fujino Junya , Yoshihara Yujiro , Nakamura Motoaki , Aoki Ryuta , Ohta Haruhisa , Sakai Yuki , Takamura Masahiro , Ichikawa Naho , Okada Go , Okada Naohiro , Kasai Kiyoto , Tanaka Saori C. , Imamizu Hiroshi , Kato Nobumasa , Okamoto Yasumasa , Takahashi Hidehiko , Kawato Mitsuo , Yamashita Okito , Hashimoto Ryu-ichiro
Published: March 2023

Autism spectrum disorder (ASD) is a lifelong condition, and its underlying biological mechanisms remain elusive. The complexity of various factors, including inter-site and development-related differences, makes it challenging to develop generalizable neuroimaging-based biomarkers for ASD. This study used a large-scale, multi-site dataset of 730 Japanese adults to develop a generalizable neuromarker for ASD across independent sites (U.S., Belgium, and Japan) and different developmental stages (children and adolescents). Our adult ASD neuromarker achieved successful generalization for the US and Belgium adults (area under the curve [AUC] = 0.70) and Japanese adults (AUC = 0.81). The neuromarker demonstrated significant generalization for children (AUC = 0.66) and adolescents (AUC = 0.71; allP<0.05, family-wise-error corrected). We identified 141 functional connections (FCs) important for discriminating individuals with ASD from TDCs. These FCs largely centered on social brain regions such as the amygdala, hippocampus, dorsomedial and ventromedial prefrontal cortices, and temporal cortices. Finally, we mapped schizophrenia (SCZ) and major depressive disorder (MDD) onto the biological axis defined by the neuromarker and explored the biological continuity of ASD with SCZ and MDD. We observed that SCZ, but not MDD, was located proximate to ASD on the biological dimension defined by the ASD neuromarker. The successful generalization in multifarious datasets and the observed relations of ASD with SCZ on the biological dimensions provide new insights for a deeper understanding of ASD.
PRMT1 Inhibition Selectively Targets BNC1-Dependent Proliferation, but not Migration in Squamous Cell Carcinoma
Authors: Boudra Rafik , Patenall Bethany L. , King Sandra , Wang Diana , Best Sarah A. , Ko Joo Yeon , Xu Shuyun , Padilla Maria G. , Schmults Chrysalyne D. , Barthel Steven R. , Lian Christine G. , Ramsey Matthew R.
Published: March 2023

Squamous Cell Carcinoma (SCC) develops in stratified epithelial tissues and demonstrates frequent alterations in transcriptional regulators. We sought to discover SCC-specific transcriptional programs and identified the transcription factor Basonuclin 1 (BNC1) as highly expressed in SCC compared to other tumor types. RNA-seq and ChIP-seq analysis identified pro-proliferative genes activated by BNC1 in SCC cells and keratinocytes. Inhibition of BNC1 in SCC cells suppressed proliferation and increased migration via FRA1. In contrast, BNC1 reduction in keratinocytes caused differentiation, which was abrogated by IRF6 knockdown, leading to increased migration. Protein interactome analysis identified PRMT1 as a co-activator of BNC1-dependent proliferative genes. Inhibition of PRMT1 resulted in a dose-dependent reduction in SCC cell proliferation without increasing migration. Importantly, therapeutic inhibition of PRMT1 in SCC xenografts significantly reduced tumor size, resembling functional effects of BNC1 knockdown. Together, we identify BNC1-PRMT1 as an SCC-lineage specific transcriptional axis that promotes cancer growth, which can be therapeutically targeted to inhibit SCC tumorigenesis.

Abstract Figure
APOL1 kidney risk variants in glomerular diseases modeled in transgenic mice
Authors: Yoshida Teruhiko , Latt Khun Zaw , Santo Briana A. , Shrivastav Shashi , Zhao Yongmei , Fenaroli Paride , Chung Joon-Yong , Hewitt Stephen M. , Tutino Vincent M. , Sarder Pinaki , Rosenberg Avi Z. , Winkler Cheryl A. , Kopp Jeffrey B.
Published: March 2023

APOL1high-risk variants partially explain the high kidney disease prevalence among African ancestry individuals. Many mechanisms have been reported in cell culture models, but few have been demonstrated in mouse models. Here we characterize two models: (1) HIV- associated nephropathy (HIVAN) Tg26 mice crossed with bacterial artificial chromosome (BAC)/APOL1 transgenic mice and (2) interferon-ψ administered to BAC/APOL1 mice. Both models showed exacerbated glomerular disease in APOL1-G1 compared to APOL1-G0 mice. HIVAN model glomerular bulk RNA-seq identified synergistic podocyte-damaging pathways activated by the APOL1-G1 allele and by HIV transgenes. Single-nuclear RNA-seq revealed podocyte-specific patterns of differentially-expressed genes as a function of APOL1 alleles. Eukaryotic Initiation factor-2 pathway was the most activated pathway in the interferon-ψ model and the most deactivated pathway in the HIVAN model. HIVAN mouse model podocyte single-nuclear RNA-seq data showed similarity to human focal segmental glomerulosclerosis (FSGS) glomerular bulk RNA-seq data. Furthermore, single-nuclear RNA-seq data from interferon-ψ mouse model podocytes (in vivo) showed similarity to human FSGS single-cell RNA- seq data from urine podocytes (ex vivo) and from human podocyte cell lines (in vitro) using bulk RNA-seq. These data highlight differences in the transcriptional effects of theAPOL1-G1 risk variant in a model specific manner. Shared differentially expressed genes in podocytes in both mouse models suggest possible novel glomerular damage markers inAPOL1variant-induced diseases. Transcription factorZbtb16was downregulated in podocytes and endothelial cells in both models, possibly contributing to glucocorticoid-resistance. In summary, these findings in two mouse models suggest both shared and distinct therapeutic opportunities for APOL1 glomerulopathies.

Significance statement

Coding variants in APOL1, encoding apolipoprotein L1, contribute to kidney disease in individuals with African ancestry. The mechanisms for glomerular injury remain incompletely understood. We studied two transgenic mouse models, HIV-associated nephropathy and interferon-ψ administration. Using glomerular and single-nuclear RNA sequencing, we identified genes differentially expressed among mice with kidney risk alleles (G1) and the common variant (G0). Both models exhibited up-regulation of genes that indicated podocyte damage with risk alleles compared to the common variant. One gene down-regulated in both models was Zbtb16, encoding a transcription factor, that may contribute to glucocorticoid-resistance. Overall, the findings suggest both shared and distinct alterations in the two disease models.
Drivers of species knowledge across the Tree of Life
Authors: Mammola Stefano , Adamo Martino , Antić Dragan , Calevo Jacopo , Cancellario Tommaso , Cardoso Pedro , Chamberlain Dan , Chialva Matteo , Durucan Furkan , Fontaneto Diego , Gonçalves Duarte V. , Martínez Alejandro , Santini Luca , Rubio-López Iñigo , Sousa Ronaldo , Villegas-Ríos David , Verdes Aida , Correia Ricardo A.
Published: March 2023

Knowledge of biodiversity is unevenly distributed across the Tree of Life. In the long run, such disparity in awareness unbalances our understanding of life on Earth, influencing policy decisions and the allocation of research and conservation funding. We investigated how humans accumulate knowledge of biodiversity by searching for consistent relationships between scientific (number of publications) and societal (number of views in Wikipedia) interest, and species-level morphological, ecological and socio-cultural factors. Across a random selection of 3,019 species spanning 29 Phyla/Divisions, we show that socio-cultural factors are the most important correlates of scientific and societal interest in biodiversity, including the fact that a species is useful or harmful to humans, has a common name and is listed in the IUCN Red List. Furthermore, large-bodied, broadly distributed and taxonomically unique species receive more scientific and societal attention, whereas colorfulness and phylogenetic proximity to humans correlates exclusively with societal attention. These results highlight a favoritism towards limited branches of the Tree of Life, and that scientific and societal priorities in biodiversity research broadly align. This suggests that we may be missing out on key species in our research and conservation agenda simply because they are not on our cultural radar.
Accurately estimating pathway activity in single cells for clustering and differential analysis
Authors: Davis Daniel , Wizel Avishai , Drier Yotam
Published: March 2023

Inferring which and how biological pathways and gene sets are changing is a key question in many studies that utilize single-cell RNA sequencing. Typically, these questions are addressed by quantifying the enrichment of known gene sets in lists of genes derived from global analysis. Here we offer SiPSiC, a new method to infer pathway activity in each cell. This allows more sensitive differential analysis and utilizing pathway scores to cluster cells and compute UMAP or other similar projections. We apply our method on datasets of COVID-19, lung adenocarcinoma and glioma, and demonstrate its utility. SiPSiC analysis is consistent with findings reported by previous analyses in many cases, but also reveals the differential activity of novel pathways, enabling us to suggest new mechanisms underlying the pathophysiology of these diseases and demonstrating SiPSiC’s high accuracy and sensitivity in detecting biological function and traits. In addition, we demonstrate how it can be used to better classify cells based on activity of biological pathways instead of single genes and its ability to overcome patient specific artifacts.
A rationally designed inactivatedSalmonellaTyphimurium vaccine induces strong and long-lasting immune responses in pigs
Authors: Lentsch Verena , Aslani Selma , Echtermann Thomas , Preet Swapan , Barazzone Elisa Cappio , Hoces Daniel , Moresi Claudia , Kuemmerlen Dolf , Slack Emma
Published: March 2023

Salmonella entericasubspeciesentericaserovar Typhimurium (S.Tm) poses a considerable threat to public health due to its zoonotic potential. Human infections are mostly foodborne, and pork and pork products are ranked among the top culprits for transmission. In addition, the high percentage of antibiotic resistance, especially in monophasicS.Tm, limits treatment options when needed. BetterS.Tm control would therefore be of benefit both for farm animals and for safety of the human food chain.

A promising pre-harvest intervention is vaccination. In this study we tested safety and immunogenicity of an oral inactivatedS.Tm vaccine, which has been recently shown to generate an “evolutionary trap” and to massively reduceS.Tm colonization and transmission in mice. We show that this vaccine is highly immunogenic and safe in post-weaning pigs and that administration of a single oral dose results in a strong and long-lasting serum IgG response. This has several advantages over existing – mainly live – vaccines againstS.Tm, both in improved seroconversion and reduced risk of vaccine-strain persistence and reversion to virulence.
Modelling how curved active proteins and shear flow pattern cellular shape and motility
Authors: Sadhukhan Shubhadeep , Penič Samo , Iglič Aleš , Gov Nir
Published: March 2023

Cell spreading and motility on an adhesive substrate are driven by the active physical forces generated by the actin cytoskeleton. We have recently shown that coupling curved membrane complexes to protrusive forces, exerted by the actin polymerization that they recruit, provides a mechanism that can give rise to spontaneous membrane shapes and patterns. In the presence of an adhesive substrate, this model was shown to give rise to an emergent motile phenotype, resembling a motile cell. Here, we utilize this “minimal-cell” model to explore the impact of external shear flow on the cell shape and migration on a uniform adhesive flat substrate. We find that in the presence of shear the motile cell reorients such that its leading edge, where the curved active proteins aggregate, faces the shear flow. The flow-facing configuration is found to minimize the adhesion energy by allowing the cell to spread more efficiently over the substrate. For the non-motile vesicle shapes, we find that they mostly slide and roll with the shear flow. We compare these theoretical results with experimental observations, and suggest that the tendency of many cell types to move against the flow may arise from the very general, and non-cell-type-specific mechanism predicted by our model.
Transcriptional regulation of the synthesis and secretion of farnesol in the fungusCandida albicans:Examination of the Homann transcription regulator knockout collection
Authors: Gutzmann Daniel J. , Kramer Jaxon J. , Toomey Brigid M. , Boone Cory H. T. , Atkin Audrey L. , Nickerson Kenneth W.
Published: March 2023

Candida albicansis an efficient colonizer of human gastrointestinal tracts and skin and is an opportunistic pathogen.C. albicansexhibits morphological plasticity and the ability to switch between yeast and filamentous morphologies is associated with virulence. One regulator of this switch is the quorum sensing molecule farnesol which is produced byC. albicansthroughout growth. However, the synthesis, secretion, regulation, and turnover of farnesol is not fully understood. To address this, we used our improved farnesol assay to screen a transcription regulator knockout library of 164 mutants for farnesol accumulation in whole cultures, pellets, and supernatants. All mutants produced farnesol and they averaged 9.2X more farnesol in the pellet than the supernatant. Nineteen mutants had significant differences with ten mutants producing more farnesol than their SN152+parent while nine produced less. Seven mutants exhibited greater secretion of farnesol while two exhibited less. We examined the time course for farnesol accumulation in six mutants with the greatest accumulation differences and found that those differences persisted throughout growth and they were not time dependent. Significantly, two high accumulating mutants did not exhibit the decay in farnesol levels during stationary phase characteristic of wild typeC. albicans, suggesting that a farnesol modification/degradation mechanism is absent in these mutants. Identifying these transcriptional regulators provides new insight into farnesol’s physiological functions regarding cell cycle progression, white-opaque switching, yeast-mycelial dimorphism, and response to cellular stress.
Variation of wine preference amongst consumers is influenced by the composition of salivary proteins
Authors: Luo Jiaqiang , Ruan Xinwei , Ang Ching-Seng , Nolvachai Yada , Marriott Philip J. , Zhang Pangzhen , Howell Kate
Published: March 2023

The preferences of consumers for different flavours and aromas in wine are varied and may be explained by inherent factors such as cultural background, wine education and personal taste of the wine consumer. Wine flavour as perceived in the mouth includes aroma compounds released through the retronasal pathway which are shaped by interactions with saliva. Saliva and wine interactions could provide an explanation as to why wine tasters express different preferences for wine. To test this hypothesis, 13 Western and 13 Chinese experienced wine tasters were recruited. Sensory evaluation was performed in formal surroundings to acquire free description-based and perceived sensory intensity data using the Pivot®Profile and continuous scale assessment, respectively. Participants’ saliva samples were collected before the sensory evaluation and spiked into a wine sample to investigate the impact on the wine volatile release using GC×GC−MS. Saliva samples were subjected to enzyme activity assays and protein composition profiling by Tandem Mass Tag (TMT) quantitative proteomics. The wine tasters showed differences in wine flavour perception, which was supported by the difference in wine volatile release resulting from the addition of saliva. The two groups of participants did not have significant differences in total salivary protein concentrations or the amounts of esterase and α-amylase. However, statistically significant variations in the concentrations of specific proteins (proline-rich proteins (PRPs) and lipocalin-1 (LCN-1);p< 0.01) were found between the two groups. Significant correlations between perceived intensities of wine attributes and concentrations of PRPs and LCN-1 were observed. These results indicate that the composition of proteins in saliva are a factor that influences wine perception and preference. Our results provide a biochemical basis to understanding preference for food based on interactions between aroma compounds and salivary proteins and could be used to suggest foods or beverages to particular cultural groups.
Site-specific Effector Protein Functionalization to Create Bead-based Avidity Model Systems
Authors: Hackl Markus , Jayachandran Dharanidaran , Ramdin Khovesh , Zhong Tong , Chundawat Shishir P.S.
Published: March 2023

The cooperative effect of multiple affinity binding interactions creating a stable bond, known as avidity, is particularly important in assessing the potency of potential drugs such as monoclonal antibodies, CAR T, or NK cells to treat cancer. However, predicting avidity based onin vitrosingle affinity interactions has limitations and often fails to describe the avidity effects observedin vivo. Acoustic force-based assays have recently emerged as a reliable method for direct avidity measurements, expressed as adhesion forces, which positively correlate with drug efficacy. However, to better understand avidity, in particular for cell-cell interactions and correlate it with affinity, a cell model system with controlled avidity-related properties is needed. This study presents a method for producing a cell model system using “effector beads” that can be used in acoustic force spectroscopy-based avidity assays or any other bead-based avidity assay. The protein of interest is biotinylatedin vivoinE.coli, purified and subsequently mixed with streptavidin coated beads to create effector beads. The results demonstrate the dependency of rupture force on the receptor surface density and force loading rate, thus providing valuable information for designing future effector bead assays as well as cell avidity measurements for screening and characterization purposes.
Sustainable and healthy purchasing behaviors towards palm oil-based food in Italy
Authors: Baldassarre Fabrizio Flavio , Santovito Savino , Campo Raffaele , Dilorenzo Giacomo
Published: March 2023

Purpose

Palm oil is widely used in the food industry; however, there are two main controversies connected to its use, namely, its nutritional value and the environmental consequences deriving from its crop. In Italy, the use of palm oil has recently been criticized, insomuch that some important bakery companies decided to substitute it, creating a real food marketing case. Through a focus on biscuits, this study is aimed at profiling consumers with regard to palm oil issue to better comprehend if the presence of this ingredient truly influences their food purchases and if they care about the nutritional and environmental aspects, highlighting the impact of the Covid-19 pandemic on consumers' consumption.

Design/methodology/approach

A questionnaire was administered to 243 subjects in Italy, in order to apply a cluster analysis.

Findings

The findings show the presence of three main kinds of consumers: (1) compromise finders (sensitive to cost savings but trying to privilege palm-oil free food), (2) brand-loyal consumers (palm oil does not influence their preferences) and (3) healthsensitives (the presence of palm oil profoundly affects their choices), who represent the majority of our sample. The results and implications are discussed.

Originality/value

Research on palm oil is essentially focused on chemistry, natural sciences or on its industrial uses: this study analyzes the consumer point of view by applying a different methodology compared to existing studies.
Rising to the challenge: adult student perceptions of institutional supports to increase access to careers in biotechnology
Authors: Portnoy Lindsay , Sadler Ash , Zulick Elizabeth
Published: March 2023

Purpose

Amidst continued calls for the democratization of access to higher education for historically underrepresented populations alongside the first global health crisis in a century lies the opportunity to address persistent societal needs: increasing access for underrepresented minority students to educational pathways that lead to careers in lucrative fields of science, technology, engineering and math (STEM).

Design/methodology/approach

Student participants enrolled in the biotechnology pathway Associates, Bachelors and Masters programs share programmatic experience in an accelerated biotechnology program through a bi-annual survey grounded in the central tenets of social-cognitive career theory aimed at understanding requisite academic, social and financial support for student success.

Findings

The pathway program described in this paper emerged to address the need to support underrepresented students in degree attainment and taking on roles in the growing field of biotechnology through a novel, multi-degree, multi-institutional pathway to STEM degree attainment and career success.

Social implications

This work has advanced understanding about how to effectively align higher education institutions with each other and with evolving STEM labor market demands while documenting the impact of essential academic, career and social supports recognized in the literature as high impact practices in broadening participation and increasing retention of underrepresented minority students in lucrative STEM careers.

Originality/value

Pathway programs which best support student success include robust mentoring, experiential learning and robust student scholarship support, part of the design of this unique pathway program. The authors share how this program utilizes high impact practices to provide low-income, underrepresented minority students with supportive, accelerated biotechnology degrees in preparation for success in the job market. What's more, of all our BS-level graduates thus far, 100% are employed and 93% within the biotechnology field. For many, the opportunity to raise their family out of poverty via a stable, high paying job is directly tied to their successes within this program.
The experiences of people with intellectual disabilities who have been convicted of sexual offences of being recalled back to prison
Authors: Rawdon Nikki , Wheatley Rachael
Published: March 2023

Purpose

This study provides further insight into the experiences of five men who have committed sexual offences, with intellectual disabilities and have been recalled back to prison. The purpose of this paper is to increase professional knowledge to assist with improving working practices that support the reintegration of individuals convicted of sexual offences and with intellectual disabilities, back into the community.

Design/methodology/approach

Interview data was analysed using interpretative phenomenological analysis, to identify the key issues associated with criminal justice services.

Findings

The following superordinate themes were identified: “The label that sticks” and “Probation officer dependency”.

Research limitations/implications

The key implications of the findings were the high level of dependency individuals had on their probation officers and the impact that this relationship had on the overall experience of recall. The stigma of the label “sex offender” was also found to have a profound impact on individuals’ feelings of safety and their future progression.

Originality/value

Research exploring the experiences of individuals convicted for sexual offences and with intellectual disabilities, being recalled back to prison, is limited. Future recommendations of how practice could be improved to better support responsivity needs of this group and to create a more positive self-identity are discussed.
Glyphosate has a negligible impact on bacterial diversity and dynamics during composting
Authors: Grenier Vanessa , Laur Joan , Gonzalez Emmanuel , Pitre Frederic E.
Published: March 2023

The herbicide glyphosate has several potential entry points into composting sites and its impact on composting processes has not yet been evaluated. To assess its impact on bacterial diversity and abundance as well as on community composition and dynamics, we conducted a mesocosm experiment at the Montreal Botanical Garden. Glyphosate had no effect on physicochemical property evolution during composting, while it was completely dissipated by the end of the experiment. Sampling at Days 0, 2, 28 and 112 of the process followed by 16S rRNA amplicon sequencing also found no effect of glyphosate on species richness and community composition. Differential abundance analyses revealed an increase of a few taxa in the presence of glyphosate, namely TRA3‐20 (order Polyangiales), Pedosphaeraceae and BIrii41 (order Burkholderiales) after 28 days. In addition, five amplicon sequence variants (ASVs) had lower relative abundance in the glyphosate treatment compared to the control on Day 2, namely Comamonadaceae,Pseudomonassp.,Streptomycessp.,Thermoclostridiumsp. andActinomadura keratinilytica, while two ASVs were less abundant on Day 112, namelyPedomicrobiumsp. andPseudorhodoplanessp. Most differences in abundance were measured between the different sampling points within each treatment. These results present glyphosate as a poor determinant of species recruitment during composting.
All the news that is fit to print? Reporting on a victim's character during a crisis
Authors: Laufer Daniel , Einwiller Sabine , Neureiter Ariadne
Published: March 2023

Using the United Airlines “bumpgate” crisis as example, this research analyses how reporting of irrelevant information on a crisis victim's bad character impacts on empathy towards the victim, the victim's reputation as well as the reputation of the news medium that published the information. A one‐factorial experiment was conducted with two conditions manipulating the reporting on the crisis victim's character plus a control condition. Respondents were 245 online‐panel participants from the UK. The findings show that when journalists violate the code of ethics by reporting irrelevant negative information on the character of a crisis victim, they harm not only the reputation of the victim, but also that of their news organization. This study contributes to the scarce research on the impact of media reporting during a crisis on victims of the crisis and on the reputation of the newspaper. Journalists must be aware that violating the journalistic code of ethics by reporting on irrelevant negative characteristics of a victim is not only detrimental for the victim but can also significantly hurt the reputation of their organization.
Correlates of sedentary behavior in people with fibromyalgia: A systematic review
Authors: Vancampfort Davy , Brunner Emanuel , McGrath Ryan L. , Hemmings Laura , Van Damme Tine
Published: March 2023

Introduction

Understanding the correlates of sedentary behavior (SB) is important in the development of interventions which reduce and interrupt SB in people with fibromyalgia (PwF). This systematic review aimed to investigate the correlates of SB in PwF using the socio‐ecological model.

Methods

Three databases (Embase, CINAHL and PubMed) were search from inception until July 21, 2022 using “sedentary” or different types of SB and “fibromyalgia” or “fibrositis” as keywords. The data collected was then analyzed using summary coding.

Results

Out of 23 SB correlates retrieved from 7 reports (n = 1698), no correlates were consistently reported (ie, reported in 4 or more studies). Higher pain intensity was the most commonly reported barrier for reducing/interrupting SB (reported in 3 reports). Other reported barriers to reducing/interrupting SB were experiencing physical and mental fatigue, a more severe disease impact, and a lack of motivation to be physically active (all reported in 1 study). A better experienced social and physical functioning and more vitality were facilitators for reducing/interrupting SB (all reported in 1 study). To date, in PwF no correlates of SB at the interpersonal, environmental and policy levels have been explored.

Conclusion

Research on correlates of SB in PwF is still in its infancy. The current preliminary evidence suggests that clinicians should consider physical and mental barriers when aiming to reduce or interrupt SB in PwF. Further research on modifiable correlates at all levels of the socio‐ecological model is required to inform future trials aiming to modify SB in this vulnerable population.
Pomalidomide and dexamethasone until progression after first salvage therapy in multiple myeloma
Authors: Garderet Laurent , Kuhnowski Frederique , Berge Benoit , Roussel Murielle , Devlamynck Laure , Petillon Marie Odile , Escoffre‐Barbe Martine , Lafon Ingrid , Facon Thierry , Leleu Xavier , Karlin Lionel , Perrot Aurore , Stoppa Anne‐Marie , Royer Bruno , Chaleteix Carine , Tiab Mourad , Araujo Carla , Lenain Pascal , Macro Margaret , Belhadj Karim , Ikhlef Souhila , Hulin Cyrille , Loiseau Herve Avet , Attal Michel , Moreau Philippe
Published: March 2023

Lenalidomide maintenance in myeloma is well established. Nevertheless, pomalidomide could provide an alternative. Myeloma patients in first relapse, initially treated in the Intergroupe Francophone du Myélome (IFM) 2009 trial, and subsequently in the IFM 2013‐01 phase 2 trial, received four cycles of salvage therapy with pomalidomide plus cyclophosphamide plus dexamethasone (PCD) with transplantation plus 2 PCD consolidation or without transplantation but with 5 PCD and for all patients pomalidomide plus dexamethasone maintenance therapy. This consisted of 28‐day cycles of pomalidomide 4 mg daily on days 1–21 and dexamethasone 20 mg weekly until progression. The primary endpoint was an improved response to treatment. A total of 75/100 patients reached therapy. The median follow‐up time was 73 months. The median duration of treatment was 23.7 months. One third of patients improved their response from the initiation of treatment: 11%, 19% and 4% to a very good partial response, complete response or stringent complete response respectively. The median progression‐free survival time was 33.2 months and the median overall survival time was not reached. Among the 75 patients, the reasons for pomalidomide discontinuation were progressive disease (54%), adverse events (AEs) (30%), investigator discretion (11%) and consent withdrawal (5%). Grade (G) 3/4 haematological AEs included neutropenia (51%) and lymphopenia (35%); G3/4 drug‐related non‐haematological AEs (>5%) comprised 13% infections. Long‐term administration of pomalidomide and dexamethasone is feasible and one third of the patients improved their response.