bluuebunny/crossref_metadata_2025 huggingface dataset:
Fibromyalgia in women: association of inflammatory plasma proteins, muscle blood flow, and metabolism with body mass index and pain characteristics
Authors: Ghafouri Bijar , Edman Emelie , Löf Marie , Lund Eva , Leinhard Olof Dahlqvist , Lundberg Peter , Forsgren Mikael Fredrik , Gerdle Björn , Dong Huan-Ji
Published: October 2022

Introduction:

Obesity is a common comorbidity in fibromyalgia (FM). Both FM and obesity have been connected to low-grade inflammation, although it is possible that previously reported inflammatory alterations in FM primarily may be linked to increased body mass index (BMI).

Objective:

This study aimed to investigate whether the inflammatory plasma protein profile, muscle blood flow, and metabolism and pain characteristics (clinical parameters and patient-reported outcome measurements) differed between female patients with FM with and without obesity.

Methods:

Patients with FM underwent clinical examinations, physical tests, and answered questionnaires. They were dichotomized according to BMI (<30 kg/m2 [n = 14]; ≥30 kg/m2 [n = 13]). Blood samples were collected and analyzed using a panel of 71 inflammatory plasma proteins.

Results:

There were significant (P < 0.05) differences in blood pressure, pulse, max VO2, pain intensity, physical capacity, and Fibromyalgia Impact Questionnaire between the groups; the obese group had higher blood pressure, pulse, pain intensity, and Fibromyalgia Impact Questionnaire. There were 14 proteins that contributed to the group belonging. The 4 most important proteins for the group discrimination were MIP1β, MCP4, IL1RA, and IL6, which showed higher concentrations in obese patients with FM. Significantly decreased blood flow and increased concentration of pyruvate were detected in obese patients compared with nonobese patients. There was significant correlation between inflammatory proteins and sedentary behavior and health status in obese patients with FM.

Conclusions:

These findings suggest that metabolism and inflammation interact in female patients with FM with obesity and might cause chronic low-grade inflammation. Screening for obesity and monitoring of BMI changes should be considered in the treatment of patients with FM.
Somatoform Symptoms in Parkinson Disease
Authors: Glovinsky David , Gruber-Baldini Ann L. , Himelhoch Seth , Anderson Karen E. , Shulman Lisa M.
Published: October 2022

Background:

Co-occurring somatoform symptoms complicate the diagnosis and treatment of Parkinson disease (PD).

Objective:

To learn more about the relationship between somatoform symptoms and PD by comparing demographic and clinical features across PD groups differing in somatoform symptom severity.

Method:

Using standardized Brief Symptom Inventory—18 (BSI–18) scores to measure somatoform symptom severity, we assigned 1093 individuals with PD to one of four subgroups using comparisons to normative means: low (M < –½ SD), average (M ± ½ SD), high (M +½ SD to +1 SD), very high (M > +1 SD). We used demographics and disease severity measures to assess each subgroup.

Results:

Most of the individuals with PD (56%) had high or very high somatoform symptom levels. Increased somatoform symptom levels were associated with female gender, lower socioeconomic status, greater disease duration, increased PD severity (Total Unified Parkinson’s Disease Rating Scale), greater disability (Older Americans Resource and Services Disability subscale), increased BSI–18 Depression and Anxiety subscale scores, lower cognitive function (Mini-Mental State Examination), lower self-efficacy scores (Self-Efficacy to Manage Chronic Disease Scale), lower quality of life scores (SF–12 Health Status Survey), and greater medical comorbidity (Cumulative Illness Rating Scale—Geriatrics) (all comparisons: P < 0.001). We found no significant between-group differences for age, race, or marital status.

Conclusion:

Somatoform symptom severity in individuals with PD is associated with greater PD severity and disability and is more common in females and in individuals with low socioeconomic status. Greater awareness of somatoform symptoms should help improve PD treatment.
Human infections caused by Streptococcus canis. A case series and description of a zoonotic infection in a northern Spain university hospital.
Authors: Fernández Vecilla Domingo , Díaz de Tuesta del Arco José Luis
Published: October 2022

Streptococcus canis is a β-hemolytic streptococcus first described in 1986. It belongs to Lancefield's group G and is part of the commensal flora of the skin and mucosa of the urinary, gastrointestinal and reproductive tract, mainly in dogs and cats. The first human infection by this microorganism was described in 1997 in a patient with sepsis. We conducted a retrospective descriptive study by reviewing medical records of all patients presenting with a positive culture of S. canis between December 2017 and June 2022, both as a pure culture and accompanied by other microorganisms. Thirty-nine patients (18 males and 21 females) with a mean of 51.2 years and median of 51 years (range, 5 to 90 years) were included. This series demonstrates the ability of S. canis to produce serious infections in humans.
Technologies to decontaminate bacterial biofilm on hospital surfaces: a potential new role for cold plasma?
Authors: Fallon Muireann , Kennedy Sarah , Daniels Stephen , Humphreys Hilary
Published: October 2022

Healthcare-associated infections (HCAIs) are a major challenge and the near patient surface is important in harbouring causes such as methicillin-resistant

Staphylococcus aureus

(MRSA) and

Clostridioides difficile

. Current approaches to decontamination are sub-optimal and many studies have demonstrated that microbial causes of HCAIs may persist with onward transmission. This may be due to the capacity of these microbes to survive in biofilms on surfaces. New technologies to enhance hospital decontamination may have a role in addressing this challenge. We have reviewed current technologies such as UV light and hydrogen peroxide and also assessed the potential use of cold atmospheric pressure plasma (CAPP) in surface decontamination. The antimicrobial mechanisms of CAPP are not fully understood but the production of reactive oxygen and other species is believed to be important. CAPP systems have been shown to partially or completely remove a variety of biofilms including those caused by Candida albicans, and multi-drug-resistant bacteria such as MRSA. There are some studies that suggest promise for CAPP in the challenge of surface decontamination in the healthcare setting. However, further work is required to define better the mechanism of action. We need to know what surfaces are most amenable to treatment, how microbial components and the maturity of biofilms may affect successful treatment, and how would CAPP be used in the clinical setting.
After NICU Discharge: Preterm Infant Feeding and Growth Through the First Year
Authors: Fernández Cristina R.
Published: October 2022

Background

Little is known about preterm infant feeding and growth in the outpatient community setting and there are no standardized post-hospital discharge feeding guidelines.

Objective

To describe the post-neonatal intensive care unit (NICU) discharge growth trajectories of very preterm (<32 weeks gestational age (GA)) and moderately preterm (32-34 6/7 weeks GA) infants managed by community pediatric providers and to determine the association between post-discharge feeding type and growth Z-scores and z-score changes through 12 months corrected age (CA).

Methods

Very preterm infants (n=104) and moderately preterm infants (n=109) born 2010-2014 and followed in hospital-affiliated community health clinics were enrolled in a single-center retrospective cohort study. Infant home feeding type and anthropometry were abstracted from outpatient medical chart review, and repeated measures analysis of variance calculated adjusted growth z-scores and z-score differences between 4 and 12 months CA. Linear regression models tested the relationship between type of home feeding at 4 months CA and anthropometry at 12 months CA.

Results

By 12 months CA, 5% of very preterm and 10% of moderately preterm infants were overweight. Moderately preterm infants on nutrient-enriched vs. standard term feeds had lower length z-scores at 12 months CA (−0.04 vs. 0.37, P=.03). Feeding type at 4 months CA predicted 12 month CA body mass index z-scores for very preterm infants (β=-0.66(−1.28, -0.04)).

Conclusion

Community pediatric providers may manage preterm infant post-NICU discharge feeding in the context of growth. Further research is needed to explore modifiable drivers of obesity risk in preterm infants to optimize infant development.
Effectiveness and duration of a second COVID-19 vaccine booster
Authors: Jara Alejandro , Cuadrado Cristobal , Undurraga Eduardo A. , García Christian , Nájera Manuel , Bertoglia María Paz , Vergara Verónica , Fernández Jorge , Garcia Heriberto , Araos Rafael
Published: October 2022

Using a prospective national cohort of 3.75 million individuals aged 20 or older, we evaluated the effectiveness against COVID-19 related ICU admissions and death of mRNA-based second vaccine boosters for four different three-dose background regimes: BNT162b2 primary series plus a homologous booster, and CoronaVac primary series plus an mRNA booster, a homologous booster, and a ChAdOx-1 booster. We estimated the vaccine effectiveness weekly from February 14 to August 15, 2022, by estimating hazard ratios of immunization over non-vaccination, accounting for relevant confounders. The overall adjusted effectiveness of a second mRNA booster shot was 88.2% (95%CI, 86.2-89.9) and 90.5% (95%CI 89.4-91.4) against ICU admissions and death, respectively. Vaccine effectiveness showed a mild decrease for all regimens and outcomes, probably associated with the introduction of BA.4 and BA.5 Omicron sub-lineages and immunity waning. The duration of effectiveness suggests that no additional boosters are needed six months following a second booster shot.
Interpretable deep learning architectures for improving drug response prediction performance: myth or reality?
Authors: Li Yihui , Hostallero David Earl , Emad Amin
Published: October 2022

Motivation: Recent advances in deep learning model development have enabled more accurate prediction of drug response in cancer. However, the black-box nature of these models still remains a hurdle in their adoption for precision cancer medicine. Recent efforts have focused on making these models interpretable by incorporating signaling pathway information in model architecture. While these models improve interpretability, it is unclear whether this higher interpretability comes at the cost of less accurate predictions, or a prediction improvement can also be obtained. Results: In this study, we comprehensively and systematically assessed four state-of-the-art interpretable models developed for drug response prediction to answer this question using three pathway collections. Our results showed that models that explicitly incorporate pathway information in the form of a latent layer perform worse compared to models that incorporate this information implicitly. Moreover, in most evaluation setups the best performance is achieved using a simple black-box model. In addition, replacing the signaling pathways with randomly generated pathways shows a comparable performance for the majority of these interpretable models. Our results suggest that new interpretable models are necessary to improve the drug response prediction performance. In addition, the current study provides different baseline models and evaluation setups necessary for such new models to demonstrate their superior prediction performance. Availability and Implementation: Implementation of all methods are provided inhttps://github.com/Emad-COMBINE-lab/InterpretableAI_for_DRP. Generated uniform datasets are inhttps://zenodo.org/record/7101665#.YzS79HbMKUk. Contact:amin.emad@mcgill.ca

Supplementary Information: Online-only supplementary data is available at the journal’s website.
Copper chelation inhibits TGF-βpathways and suppresses epithelial-mesenchymal transition in cancer
Authors: Poursani E. M. , Mercatelli D. , Raninga P. , Bell J. L. , Saletta F. , Kohane F. V. , Zheng Y. , Rouaen J. , Jue T. R. , Michniewicz F. T. , Kasiou E. , Tsoli M. , Cirillo G. , Waters S. , Shai-Hee T. , Valli E. , Brettle M. , Whan R. , Vahadat L. , Ziegler D. , Lock J. G. , Giorgi F. M. , Khanna K. K. , Vittorio O.
Published: October 2022

Copper is a trace element essential to cellular function with elevated levels implicated in cancer progression. Clinical trials using copper chelators are associated with improved patient survival, however, the molecular mechanisms by which copper depletion inhibits tumor progression are poorly understood. This remains a major hurdle to the clinical translation of copper chelators. Epithelial-mesenchymal transition (EMT) is often exploited by malignant cells to promote growth and metastasis. Transforming growth factor (TGF)-βis a master regulator of EMT and facilitates cancer progression through changes in the tumor and its microenvironment. Herein, we report that a reduction of copper with the chelating agent tetraethylenepentamine (TEPA) inhibited EMTin vitroin three diverse cancer cell types; human triple-negative breast cancer (TNBC), neuroblastoma (NB), and diffuse intrinsic pontine glioma (DIPG) cell lines. Single-molecule imaging demonstrated EMT markers including Vimentin,β-catenin, ZEB1, and p-SMAD2 had increased expression with copper treatment and this pro-mesenchymal shift was rescued by the addition of TEPA. Moreover, SNAI1, ZEB1, and p-SMAD2 demonstrated increased accumulation in the cytoplasm after treating with TEPA. Transcriptomic analyses revealed a significant downregulation of the EMT pathway, including canonical (TGF-β/SMAD2&3) and non-canonical (TGF-β/PI3K/AKT and TGF-β/RAS/RAF/MEK/ERK) TGF signaling pathways. Matrix metalloproteinases MMP-9 and MMP-14 proteins which activate latent TGF-βcomplexes were also downregulated by TEPA treatment. These molecular changes are consistent with reduced plasma levels of TGF-βwe observed in cancer models treated with TEPA. Importantly, copper chelation reduced metastasis to the lung in a TNBC orthotopic syngeneic mouse model. Our studies suggest copper chelation therapy can be used to inhibit EMT-induced metastasis by targeting TGF-βsignalling. Because on-target anti-TGF-βtherapies are failing in the clinic, copper chelation presents itself as a potential therapy for targeting TGF-βin cancer.
Effect of Odor Stimulations on Physical Activity: A Systematic Review
Authors: Cournoyer Mathieu , Maldera Alice , Gauthier Alexandre-Charles , Maso Fabien Dal , Mathieu Marie-Eve
Published: October 2022

Fewer and fewer people are reaching physical activity recommendations. Therefore, it seems important to make the practice of physical activity more enjoyable to increase the participation rate. Several environmental factors have been studied to see their impact on sports practice, and some studies investigated the effect of odors. This systematic review aims to provide a thorough view of the literature on the effect of different odors on physical activity. The search strategy consisted of using index terms and keywords in MEDLINE, EMBASE, EBM Reviews – Cochrane Central Register of Controlled Trials, CINAHL, SPORTDiscus, and Web of Science search engine. Data from 19 studies that included 421 participants revealed that the odors had different results on strength, cardiovascular, precision, and postural balance tasks depending on the odors’ exposition. Among results, an important distinction was made between pleasant and unpleasant odors. Therefore, pleasant odors had better results on physical activity by improving participants’ feeling. Even though this review clarified evidence about the effect of odors on physical activity, better methodological consistency is needed across studies such as the odor administration method to produce more meaningful results.
Vaccines alone cannot slow the evolution of SARS-CoV-2
Authors: Van Egeren Debra , Stoddard Madison , White Laura F. , Hochberg Natasha S. , Rogers Michael S. , Zetter Bruce , Joseph-McCarthy Diane , Chakravarty Arijit
Published: October 2022

The rapid emergence of immune-evading viral variants of SARS-CoV-2 calls into question the practicality of a vaccine-only public health strategy for managing the ongoing COVID-19 pandemic. It has been suggested that widespread vaccination is necessary to prevent the emergence of future immune-evading mutants. Here we examine that proposition using stochastic computational models of viral transmission and mutation. Specifically, we look at the likelihood of emergence of immune escape variants requiring multiple mutations, and the impact of vaccination on this process. Our results suggest that the transmission rate of intermediate SARS-CoV-2 mutants will impact the rate at which novel immune-evading variants will appear. While vaccination can lower the rate at which new variants appear, other interventions that reduce transmission can also have the same effect. Crucially, relying solely on widespread and repeated vaccination (vaccinating the entire population multiple times a year) is not sufficient to prevent the emergence of novel immune-evading strains if transmission rates remain high within the population. Thus, vaccines alone are incapable of slowing the pace of evolution of immune evasion, and vaccinal protection against severe and fatal outcomes for COVID-19 patients is therefore not assured.
Association of upper respiratory Streptococcus pneumoniae colonization with SARS-CoV-2 infection among adults
Authors: Parker Anna M. , Jackson Nicole , Awasthi Shevya , Kim Hanna , Alwan Tess , Wyllie Anne L. , Baldwin Alisha B. , Brennick Nicole B. , Moehle Erica A. , Giannikopoulos Petros , Kogut Katherine , Holland Nina , Mora-Wyrobek Ana , Eskenazi Brenda , Riley Lee W. , Lewnard Joseph A.
Published: October 2022

Background

Streptococcus pneumoniae interacts with numerous viral respiratory pathogens in the upper airway. It is unclear whether similar interactions occur with SARS-CoV-2.

Methods

We collected saliva specimens from working-age adults receiving SARS-CoV-2 molecular testing at outpatient clinics and via mobile community-outreach testing between July and November 2020 in Monterey County, California. Following bacterial culture enrichment, we tested for pneumococci by quantitative polymerase chain reaction (qPCR) targeting the lytA and piaB genes, and measured associations with SARS-CoV-2 infection via conditional logistic regression.

Results

Analyses included 1,278 participants, with 564 enrolled in clinics and 714 enrolled through outreach-based testing. Prevalence of pneumococcal carriage was 9.2% (117/1,278) among all participants (11.2% [63/564] clinic-based testing; 7.6% [54/714] outreach testing). Prevalence of SARS-CoV-2 infection was 27.4% (32/117) among pneumococcal carriers and 9.6% (112/1,161) among non-carriers (adjusted odds ratio [aOR]: 2.73; 95% confidence interval: 1.58-4.69). Associations between SARS-CoV-2 infection and pneumococcal carriage were enhanced in the clinic-based sample (aOR=4.01 [2.08-7.75]) and among symptomatic participants (aOR=3.38 [1.35-8.40]), when compared to findings within the outreach-based sample and among asymptomatic participants. Adjusted odds of SARS-CoV-2 co-infection increased 1.24 (1.00-1.55)-fold for each 1-unit decrease in piaB qPCR CT value among pneumococcal carriers. Last, pneumococcal carriage modified the association of SARS-CoV-2 infection with recent exposure to a suspected COVID-19 case (aOR=7.64 [1.91-30.7] and 3.29 [1.94-5.59]) among pneumococcal carriers and non-carriers, respectively).

Conclusions

Associations of pneumococcal carriage detection and density with SARS-CoV-2 suggest a synergistic relationship in the upper airway. Longitudinal studies are needed to determine interaction mechanisms between pneumococci and SARS-CoV-2.

Key points

In an adult ambulatory and community sample, SARS-CoV-2 infection was more prevalent among pneumococcal carriers than non-carriers.

Associations between pneumococcal carriage and SARS-CoV-2 infection were strongest among adults reporting acute symptoms and receiving SARS-CoV-2 testing in a clinical setting.
UBE2C promotes leptomeningeal dissemination and is a therapeutic target in brain metastatic disease
Authors: Paisana Eunice , Cascão Rita , Custódia Carlos , Qin Nan , Picard Daniel , Pauck David , Carvalho Tânia , Ruivo Pedro , Barreto Clara , Doutel Delfim , Cabeçadas José , Roque Rafael , Pimentel José , Miguéns José , Remke Marc , Barata João T. , Faria Claudia C.
Published: October 2022

Despite current improvements in systemic cancer treatment, brain metastases (BM) remain incurable, and there is an unmet clinical need for effective targeted therapies. Here, we sought common molecular events in brain metastatic disease. RNA sequencing of thirty human BM identified the upregulation of UBE2C, a gene that ensures the correct transition from metaphase to anaphase, across different primary tumor origins. Tissue microarray analysis of an independent BM patient cohort revealed that high expression of UBE2C was associated with decreased survival. UBE2C-driven orthotopic mouse models developed extensive leptomeningeal dissemination, likely due to increased migration and invasion. Early cancer treatment with dactolisib (dual PI3K/mTOR inhibitor) prevented the development of UBE2C-induced leptomeningeal metastases. Our findings reveal UBE2C as a key player in the development of metastatic brain disease and highlight PI3K/mTOR inhibition as a promising anticancer therapy to prevent late-stage metastatic brain cancer.
Intracellular helix-loop-helix domain modulates inactivation kinetics of mammalian TRPV5 and TRPV6 channels
Authors: Flores-Aldama Lisandra , Bustos Daniel , Cabezas-Bratesco Deny , Brauchi Sebastián E.
Published: October 2022

TRPV5 and TRPV6 are calcium-selective ion channels expressed at the apical membrane of epithelial cells. Important for systemic calcium (Ca2+) homeostasis, these channels are considered as gatekeepers of this cation transcellular transport. Intracellular Ca2+ exerts a negative control over the activity of these channels by promoting inactivation. TRPV5 and TRPV6 inactivation has been divided into fast and slow phases based on their kinetics. While slow inactivation is common to both channels, fast inactivation is characteristic of TRPV6. It has been proposed that the fast phase depends on Ca2+ binding and that the slow phase depends on the binding of the Ca2+/Calmodulin complex to the internal gate of the channels. Here, by means of structural analyses, site-directed mutagenesis, electrophysiology, and molecular dynamic simulations, we identified a specific set of amino acids and interactions that determine the inactivation kinetics of mammalian TRPV5 and TRPV6 channels. We propose that the association between the intracellular helix-loop-helix (HLH) and the TRP helix (TDh) domains favors the faster inactivation kinetics observed in mammalian TRPV6 channels.
Resolving Complexities in Taxonomic Lineages of the Organellar and Nuclear Genomes of Galdieria through Comparative Phylogenomic Analysis
Authors: Iovinella Manuela , Lock Sarah C. L. , Downing Jessica M. , Morley Jennifer , Chew Yen Peng , Mackinder Luke C. M. , Chong James P. J. , Feichtinger Georg A. , Ashton Peter D. , James Sally , Jeffares Daniel , Ciniglia Claudia , Davis Seth J.
Published: October 2022

Exploration of life in extreme environments allows the discovery of intriguing organisms with extraordinary biotechnological potential. An example of extreme environments is represented by hot springs, where harsh conditions (pH < 1; Temperature > 50°C; high concentrations of metals) are prohibitive for most living organisms, except for archaea, bacteria and a few eukaryotes like the unicellular red alga Galdieria. Phylogenetic analysis based on a few plastid and nuclear genes highlighted the intricate genetic structure of Galdieria and the hypothesis of diverging clades within the G. sulphuraria species. To resolve enigmatic relationships between lineages, we used plastid, mitochondrial and nuclear genome-scale data obtained from numerous strains from around the world. The resulting phylogenomic analysis identified: i) the divergence of each of the mitochondrial, plastid, and nuclear genomes into the same six clear lineages; ii) the independent evolution of the lineages; iii) the incongruent interlineages relationships between the three genomes. Differential evolutionary pressure between the strains and the genomes were also highlighted by synonymous and non-synonymous substitutions.
Learning Free Energy Pathways through Reinforcement Learning of Adaptive Steered Molecular Dynamics
Authors: Ho Nicholas , Cava John Kevin , Vant John , Shukla Ankita , Miratsky Jake , Turaga Pavan , Maciejewski Ross , Singharoy Abhishek
Published: October 2022

In this paper, we develop a formulation to utilize reinforcement learning and sampling-based robotics planning to derive low free energy transition pathways between two known states. Our formulation uses Jarzynski’s equality and the stiffspring approximation to obtain point estimates of energy, and construct an informed path search with atomistic resolution. At the core of this framework, is our first ever attempt we use a policy driven adaptive steered molecular dynamics (SMD) to control our molecular dynamics simulations. We show that both the reinforcement learning and robotics planning realization of the RL-guided framework can solve for pathways on toy analytical surfaces and alanine dipeptide.
Control of spatio-temporal patterning via cell density in a multicellular synthetic gene circuit
Authors: Santorelli Marco , Bhamidipati Pranav S. , Kavanagh Andriu , MacKrell Victoria A. , Sondkar Trusha , Thomson Matt , Morsut Leonardo
Published: October 2022

A major goal in synthetic development is to design and construct gene regulatory circuits that control the patterning and morphogenesis of synthetic multicellular structures. In natural development, an interplay between mechanical and chemical communication shapes the dynamics of gene regulatory circuits that underlie patterning and morphogenesis. However, for synthetic gene circuits, how the non-genetic properties of the growth environment impact circuit behavior remains poorly understood. Here, we describe an occurrence of mechano-chemical coupling in synthetic contact-dependent synNotch patterning circuits demonstrating that cell density modulates the transduction of signal between a sender and receiver cell. By exploiting density-dependent signaling, we construct multicellular signal propagation circuits with synNotch and control the patterning outcome both temporally and spatially via cell density gradients established in vitro via plating or small-molecule mediated modulation of proliferation. Our work demonstrates that synthetic gene circuits can be critically impacted by their context, providing an alternate means for programming multi-cellular circuit patterning outcomes.
Randomized, Double-Blind, Placebo-Controlled Trial of MUC1 Peptide Vaccine for Prevention of Recurrent Colorectal Adenoma
Authors: Schoen Robert E. , Boardman Lisa A. , Cruz-Correa Marcia , Bansal Ajay , Kastenberg David , Hur Chin , Dzubinski Lynda , Kaufman Sharon F. , Rodriguez Luz M. , Richmond Ellen , Umar Asad , Szabo Eva , Salazar Andres , McKolanis John , Beatty Pamela , Pai Reetesh K. , Singhi Aatur D. , Jacqueline Camille M. , Bao Riuye , Diergaarde Brenda , McMurray Ryan P. , Strand Carrie , Foster Nathan R. , Zahrieh David M. , Limburg Paul J. , Finn Olivera J.
Published: October 2022

Objective

Vaccines against antigens expressed on adenomas could prevent new adenoma formation. We assessed whether a MUC1 peptide vaccine produces an immune response and prevents subsequent colonic adenoma formation.

Design

Multicenter, double blind, placebo-controlled randomized trial in individuals age 40-70 with diagnosis of an advanced adenoma ≤1 year from randomization. Vaccine was administered at 0, 2, and 10 weeks with a booster injection at week 53. Adenoma recurrence was assessed ≥1 year from randomization. The primary endpoint was vaccine immunogenicity at 12 weeks defined by anti-MUC1 ratio ≥2.0.

Results

53 participants received the MUC1 vaccine and 50 placebo. 13/52 (25%) of MUC1 vaccine recipients had a ≥2-fold increase in MUC1 IgG (range 2.9-17.3) at week 12 vs. 0/50 placebo recipients (1-sided Fisher’s exact P<0.0001). Of the 13 responders at week 12, 11 (84.6%) had a ≥2-fold increase in MUC1 IgG with the booster and were considered immune responders. A recurrent adenoma was observed in 31 of 47 (66.0%) in the placebo group vs. 27 of 48 (56.3%) participants in the MUC1 group (adjusted relative risk (aRR) = 0.83 [95% CI, 0.60-1.14], P=0.25). Adenoma recurrence occurred in 3/11 (27.3%) immune responders, (aRR = 0.41 [95% CI, 0.15-1.11], P=0.08). Vaccine recipients had more injection site reactions than placebo recipients, but there was no difference in serious adverse events.

Conclusion

An immune response was observed only in vaccine recipients. Overall adenoma recurrence was not different than placebo, but a 38% absolute reduction in adenoma recurrence was observed in immune responders.

ClinicalTrials.gov Identifier: NCT02134925.

https://clinicaltrials.gov/ct2/show/NCT02134925

Key Points

What is already known

Antigens expressed on colonic adenomas are potential targets for immunopreventive vaccines. An effective vaccine could prevent subsequent adenoma formation.

What this Study Adds

In this multicenter, double blind, placebo-controlled randomized trial, MUC1 vaccine recipients developed an immune response. Overall adenoma recurrence was not different than placebo, but a 38% absolute reduction in adenoma recurrence was observed in immune responders.

How this study might affect research, practice or policy

Vaccine immunoprevention is a potential new frontier to colorectal cancer prevention.
The value of freedom: the introduction of option freedom in health-related capability wellbeing measurement
Authors: Ubels Jasper , Hernandez-Villafuerte Karla , Schlander Michael
Published: October 2022

The capability approach has been used to develop instruments. However, the capability concept by Sen has been argued to be ambiguous concerning some elements of freedom, such as the burdens that people experience whilst achieving capabilities. Developing instruments with a comprehensive definition of capability might increase their sensitivity to a broader range of constructs. Our study operationalizes a framework based on the comprehensive “option freedom” concept into measurable constructs and presents an illustrative instrument.

For this, the Multi Instrument Comparison (MIC) database was used. Items from the MIC database were matched to themes from a framework that had been developed in an earlier qualitative study. Then, a measurement model was constructed with the selected items and model fit was assessed. Lastly, an illustrative instrument was created that shows how the selected constructs can be measured concisely.

A measurement model was constructed with 57 items and 11 factors. Data-driven explorative adjustments were made to improve model fit. Based on this model an instrument was developed with three scales (“Reflective Wellbeing”, “Affective Wellbeing” and “Perceived Access to Options”) totaling 15 items. This instrument showed adequate psychometric characteristics in terms of reliability and fit index values.

This study shows how the concept of option freedom can be operationalized for health-related wellbeing assessment. Furthermore, the analysis indicates that in the context of outcome measurement, information about both capabilities and functionings related to subjective wellbeing is required to assess the overall wellbeing of an individual. Further research is needed to validate the instrument.
Reward-related activation of fronto-striatal regions scaled negatively with C-reactive protein but showed no association with anhedonia in depression
Authors: Aruldass Athina R. , Kitzbichler Manfred G. , Lim Tsen Vei ,   Wellcome Trust Consortium for Neuroimmunology of Mood Disorders and Alzheimer’s Disease (NIMA), Cavanagh Jonathan , Cowen Phil , Pariante Carmine M. , Bullmore Edward T. , Harrison Neil A.
Published: October 2022

Depression is characterized by divergent changes in positive and negative affect. Emerging roles of inflammation in depression portend avenues for novel immunomodulator-based monotherapy, targeting mechanistically distinct symptoms such as anhedonia and pessimism. To investigate fundamental links between these divergent affective components and inflammation, we used a probabilistic reinforcement-learning fMRI paradigm, testing for evidence of hyposensitivity to reward, and hypersensitivity to punishment in low-inflammation depression cases (loCRP depression; CRP ≤ mg/L; N=48), high-inflammation depression cases (hiCRP depression; CRP > 3mg/L; N=31), and healthy controls (HC; CRP ≤ mg/L; N=45). We aimed to (i) determine whether depression cases with high and low inflammation showed aberrant neural activation to monetary gains and losses compared to controls; (ii) examine if these alterations correlated with a continuous measure of C-reactive protein (CRP) in depression, (iii) test if neuroimaging responses to rewards and punishments scaled with indices of anhedonia and pessimism derived from behavioral instruments in depression. Voxel-wise activation was observed in key brain regions sensitive to monetary reward (ventromedial prefrontal cortex, vmPFC; nucleus accumbens, NAc) and punishment (insula) outcomes across all three groups. However, there was no significant difference in activation between groups. Within depression cases, increasing CRP scaled negatively with activation in the right vmPFC and left NAc but not insula cortex. However, there was no significant association between regional activation and severity of anhedonia or pessimism. Our results support the previously reported association between CRP and striatal reward reactivity in depression but do not extend this to processing of negatively valenced information.
Neurogenomic landscape associated with status-dependent cooperative behavior
Authors: Bolton Peri E. , Ryder T. Brandt , Dakin Roslyn , Houtz Jennifer L. , Moore Ignacio T. , Balakrishnan Christopher N. , Horton Brent M.
Published: October 2022

The neurogenomic mechanisms mediating male-male reproductive cooperative behaviors are unknown. We leveraged extensive transcriptomic and behavioral data on a neotropical bird (Pipra filicauda) that perform cooperative courtship displays to understand these mechanisms. Cooperative display is modulated by testosterone, it promotes cooperation in non-territorial birds, but suppresses cooperation in territory holders. We sought to understand the neurogenomic underpinnings of these three related traits: social status, cooperative behavior, and testosterone phenotype. To do this, we profiled gene expression in 10 brain nuclei spanning the social decision-making network (SDMN), and two key endocrine tissues that regulate social behavior. We associated gene expression with each bird’s behavioral and endocrine profile derived from three years of repeated measures taken from free-living birds in the Ecuadorian Amazon. We found distinct landscapes of constitutive gene expression were associated with social status, testosterone phenotype, and cooperation, reflecting the modular organization and engagement of neuroendocrine tissues. Sex-steroid and neuropeptide signaling appeared to be important in mediating status-specific relationships between testosterone and cooperation, suggesting shared regulatory mechanisms with male aggressive and sexual behaviors. We also identified differentially regulated genes involved in cellular activity and synaptic potentiation, suggesting multiple mechanisms underpin these genomic states. Finally, we identified SDMN-wide gene expression differences between territorial and floater males that could form the basis of “status-specific” neurophysiological phenotypes, potentially mediated by testosterone and growth hormone. Overall, our findings provide new, systems-level insights into the mechanisms of cooperative behavior and suggest that differences in neurogenomic state are the basis for individual differences in social behavior.
Emergency hematopoiesis proceeds without contribution of hematopoietic stem cells
Authors: Munz Clara M. , Dressel Nicole , Chen Minyi , Grinenko Tatyana , Roers Axel , Gerbaulet Alexander
Published: October 2022

Hematopoietic stem cells (HSCs) are the ultimate source of blood and immune cells. Under homeostatic conditions, these cells are considered a quiescent reserve population. However, it is not clear to what extent HSCs participate in emergency responses. Herein, we use fate mapping and proliferation tracking mouse models, which cumulatively record HSC activity in situ. We observed no direct contribution of HSCs to mature blood cell regeneration in response to common hematopoietic emergencies, including inflammation or blood loss. Innate immune training, in which HSCs were proposed to store and integrate information on previous infections, did not alter HSC activity upon secondary exposure. Only severe myeloablation resulted in a robust increase of HSC contribution. Our data demonstrates that HSCs do not directly participate in the regeneration of mature blood cells and therefore do not represent a reserve population to compensate for physiological hematopoietic perturbations.
CasTuner: a degron and CRISPR/Cas-based toolkit for analog tuning of endogenous gene expression
Authors: Noviello Gemma , Gjaltema Rutger A. F. , Schulz Edda G.
Published: October 2022

Certain cellular processes are dose-dependent, requiring a specific quantity of gene products or a defined stoichiometry between them. This is exemplified by haploinsufficiency or by the need for dosage compensation for X-linked genes between the sexes in many species. Understanding dosage-sensitive processes requires the ability to perturb endogenous gene products in a quantitative manner. Here we present CasTuner, a CRISPR-based toolkit that allows analog tuning of endogenous gene expression. In the CasTuner system, activity of Cas-derived repressors is controlled through a FKBP12F36Vdegron domain and can thereby be quantitatively tuned by titrating the small molecule degrader dTAG-13. The toolkit can be applied at the transcriptional level, using the histone deacetylase hHDAC4 fused to dCas9, or at the post-transcriptional level, using the RNA-targeting CasRx. To optimise efficiency, inducibility and homogeneity of repression we target a fluorescently tagged endogenous gene,Esrrb, in mouse embryonic stem cells. Through flow cytometry, we show that CasTuner allows analog tuning of the target gene in a homogeneous manner across cells, as opposed to the widely used KRAB repressor domain, which exhibits a digital mode of action. We quantify repression and derepression dynamics for CasTuner and use it to measure dose-response curves between the pluripotency factor NANOG and several of its target genes, providing evidence for target-specific dose dependencies. CasTuner thus provides an easy-to-implement tool to perturb gene expression in an inducible, tunable and reversible manner and will be useful to study dose-responsive processes within their physiological context.
Reciprocal inflammatory signaling in an ex-vivo explant model for neurofibromatosis type 1-related cutaneous neurofibromas
Authors: Grit Jamie , Turner Lisa , Essenburg Curt , Dischinger Patrick , Shurlow Nate , Pate Matt , Graveel Carrie , Steensma Matt
Published: October 2022

Cutaneous neurofibromas (CNF) are benign tumors that occur in the dermis of individuals with neurofibromatosis type 1 (NF), an inherited tumor predisposition syndrome. CNFs cause disfigurement, pain, burning, and itching, resulting in reduced quality of life in NF patients. However, due to their benign nature there are few in vitro or in vivo models of CNFs, which has limited the research of CNF biology and drug discovery efforts. To address this, we developed a patient derived explant (PDE) ex vivo culture model of CNF tumors and normal skin from NF patients. CNF PDEs remain viable in culture for over 9 days and recapitulate the cellular composition and molecular signaling of CNFs. We identified reciprocal inflammatory signaling in CNF PDEs, in which tumors rely on either prostaglandin or leukotriene mediated signaling pathways. Ex vivo glucocorticoid treatment reduced expression of pro-inflammatory genes, confirming CNF PDEs are a useful model for mechanistic studies and preclinical drug testing.
Untangling the relationship between work pressure and emotions in social media: a quantitative empirical study of construction industry
Authors: Liao Liping , Wu Zhijiang
Published: October 2022

Purpose

The booming social media attracts construction professionals (CPs) to express emotions caused by work pressure (WP) through online behaviors. Previous works focus on the analysis of WP and emotions but do not adequately consider how WP can be reflected through online emotions. Thus, this study aims to attempt to explore the quantitative relationship between online emotional intensity and WP.

Design/methodology/approach

This study developed a linguistic-sticker (LS) model to quantitatively evaluate the sentiment intensity of posts published on social media. Moreover, the authors designed two econometric models of ordinary least squares regression and negative binomial regression to test the hypothesis.

Findings

The research found that posts with stronger negative sentiment (or positive sentiment) indicate that CPs face higher (or lower) WP. Besides, there is a negative bias between the sentiment intensity of posts and the comment quantity.

Practical implications

The positive correlation between sentiment intensity of posts and WP has been confirmed, which indicates that construction managers should pay more attention to CPs' behavior on social media, and take a more direct way to analyze work-related online behavior (e.g. posting, commenting). The dynamic monitoring of emotion-related posts also provides a direct basis for the management team to learn about CP's pressure status and propose measures to reduce their negative emotions. Furthermore, the emotional posts published by CPs on social media provide a direct basis for team managers to obtain their psychological state.

Originality/value

The research contributes to incorporating CPs' emotions into the LS model and to providing information systems artifacts and new findings on the analysis of WP and online emotions.
Limited usefulness of firm-provided cybersecurity information in institutional investors’ investment analysis
Authors: Fortin Anne , Héroux Sylvie
Published: October 2022

Purpose

The purpose of this study is to examine how financial analysts deal with cybersecurity information in their investment analysis process and whether they find cybersecurity disclosures in companies’ financial reports useful.

Design/methodology/approach

Investment managers/financial analysts and chief information security officers (CISOs) at seven institutional investors were interviewed.

Findings

Not all financial analysts consider cybersecurity risk in their investment analyses. Those who do look at company strategy, how the company integrates cybersecurity into its processes and whether it has certified its cybersecurity information. The financial analysts use this qualitative information to adjust the results of their quantitative analysis. They do not find boilerplate or cursory cybersecurity information in financial reports to be useful. In fact, they view it as unreliable and prefer drawing on other information sources to assess the company’s cybersecurity risk.

Practical implications

The results of this study highlight to securities regulators that reported cybersecurity information is of limited usefulness. Regulators are challenged to revisit their disclosure requirements. Companies wishing to improve the usefulness of their cybersecurity information should provide more company-specific information.

Originality/value

To the best of the authors’ knowledge, this study is the first to look at financial analysts’ perception of cybersecurity-related information. It complements findings from prior market studies by adding new insights into the way influential market participants deal with this information in their investment analysis process.
An exploratory investigation of technology-assisted dining experiences from the consumer perspective
Authors: Gu Qiushi , Li Minglong , Huang Songshan (Sam)
Published: October 2022

Purpose

The use of modern technologies in restaurants has become a trend. For food and beverage services, embracing new technologies helps solve the dilemmas of increasing labor costs and the high level of staff turnover in the industry. However, knowledge regarding how consumers perceive and evaluate technology-assisted dining experiences (TADEs) is limited. This study aims to conceptualize and operationalize TADEs while considering increasing technological applications in restaurants.

Design/methodology/approach

This study conducted in-depth interviews with 71 restaurant consumers in Nanjing and Wuhan, China. Following the interviews, this study carried out a survey and identified the factor structure of TADEs.

Findings

The in-depth interviews identified 26 attributes of TADEs. An analysis of the survey data identified four important aspects (with 21 items) of TADEs, namely, novelty and fashion, convenience, high efficiency and restrictions and possible risks.

Practical implications

Hospitality managers can implement the suggested measures for dining service design and technology management to improve the experiences of customers.

Originality/value

These findings have theoretical implications for the new phenomenon of technology-integrated dining, the application of technology and consumer management in the catering industry.
Supervisor incivility and turnover intention of the employees in the hospitality industry of China
Authors: Yin Jie , Ji Yingchao , Ni Yensen
Published: October 2022

Purpose

As supervisor incivility and its negative effect may impact employees’ psychological health and even the sustainable development of hospitality enterprises, this study aims to explore the channels through which it affects employee turnover intention in China’s hospitality industry and suggest possible mitigation measures.

Design/methodology/approach

This study adopted exploratory factor analysis, measurement model analysis and the mediation and moderation model and used SPSS and PROCESS for the analysis.

Findings

This study found that the impact of supervisor incivility on the employees’ turnover intention would be through employees’ ego depletion and revealed that organizational support would alleviate such a negative effect. However, organizational support might not mitigate the impact of supervisor incivility on the employees’ ego depletion, which is inconsistent with previous studies. This study inferred that organizational support might be somewhat related to organizational pressure, thereby enhancing the impact of supervisor incivility on the employees’ ego depletion.

Research limitations/implications

This study not only enriches incivility literature but also suggests new insights into the mixed role of organizational support.

Originality/value

Unlike previous studies that mainly focused on workplace pressure from colleagues or customers, this study broadens our understanding of the employees’ turnover intention affected by supervisors’ workplace incivility and the mixed role of organizational support.