bluuebunny/crossref_metadata_2025 huggingface dataset:
“It Took Away the Joy:” First American Mothers' Experiences with Postpartum Depression
Authors: Heck Jennifer L. , Wilson Janet Sullivan , Parker Judy Goforth
Published: September 2021

Background:

Postpartum depression (PPD) is a devastating mental illness associated with adverse health outcomes for mother, child, and family. Higher PPD prevalence in First American women suggests a racial/ethnic disparity, yet little is known about how PPD is experienced from their perspective.

Purpose:

To 1) describe First American women's PPD experiences and the meanings they ascribe to those experiences and 2) describe the cultural knowledge, influences, and practices during the perinatal period.

Study Design and Methods:

This phenomenological study used a community-based participatory research approach. Criterion and snowball sampling captured First American women who had PPD now or in the past (N = 8). Interviews used a semistructured guide and thematic analysis followed.

Results:

Mean age was 30.25 years. Most women were multigravidas (n = 7) and rated themselves as “very” (n = 4) or “mostly” (n = 3) Native American. Women were mostly of low socioeconomic status and had a history of depression (n = 7) and/or a history of prenatal depression (n = 6). Themes: 1) stressors that contributed to PPD; 2) how PPD made me feel; 3) what made my PPD better; 4) heritage-centered practices; 5) support through PPD; 6) how I felt after PPD; and 7) am I a good mother?

Clinical Implications:

This study provides a better understanding of some First American women's PPD experiences that facilitates judgment of the importance of PPD within a cultural context. Clinicians need to create culturally appropriate responses to First American women's PPD needs.
The Potential Role of Appetite in Mediating the Relationship of Whole Grains and Body Weight
Authors: Sanders Lisa M. , Maki Kevin C.
Published: September 2021

Observational studies have consistently shown a relationship between whole grain (WG) intake and lower body weight and body weight gain over time. However, randomized controlled trials (RCTs) have not established a consistent causal relationship between WG intake and body weight. There are several plausible mechanisms for how WGs may be able to influence body weight, particularly through effects on appetite and energy intake. Recently, several systematic reviews and meta-analyses have evaluated WG intake and the relationship to body weight in observational studies and RCTs, as well as relationships to appetite and energy intake in RCTs. This review summarizes these recent findings and explores how modest changes in short-term appetite may impact energy intake and body weight in the long term. In addition, reasons for possible inconsistencies in RCTs and observational studies on body weight will be discussed, as well as the limitations of the current research and future opportunities to improve the relevance of the research for public health.
Can You Trust Dr Google for Health and Nutrition?
Authors: Cai Hannah C. , Dwyer Johanna T.
Published: September 2021

Most patients realize that the Internet is no substitute for professional advice, but they cannot resist the impulse to cruise the Web to get a second opinion from “Dr Google.” Can they trust Dr Google for health and nutrition advice?

This article describes what the Google search engine is, how it is funded, and why health professionals and consumers should be wary of using it for health and nutrition information. These search results often lack objectivity, feature unsound recommendations based on faulty evidence, and include a confusing mixture of advertisements, anecdotal reports, and even outlandish claims. The Internet is no substitute for professional advice, but it is here to stay, and we summarize ways to separate dependable from dubious search engine results.
The Relationship between High-reliability practice and Hospital-acquired conditions among the Solutions for Patient Safety Collaborative
Authors: Randall Kelly H. , Slovensky Donna , Weech-Maldonado Robert , Sharek Paul
Published: September 2021

Introduction:

Theoretically, the application of reliability principles in healthcare can improve patient safety outcomes by informing process design. As preventable harm continues to be a widespread concern in healthcare, evaluating the association between integrating high-reliability practices and patient harms will inform a patient safety strategy across the healthcare landscape. This study evaluated the association between high-reliability practices and hospital-acquired conditions.

Methods:

Twenty-five pediatric organizations participating in the Children’s Hospitals Solutions for patient safety collaborative participated in this nonexperimental design study. A survey utilizing the high-reliability healthcare maturity model assessed the extent of implementing high-reliability practices at each participating site. We analyzed responses for each component and a composite score of high reliability against an aggregate measure of hospital-acquired conditions.

Results:

Of the 95 invited sites, 49 responded and 25 were included in the final results. There was a significant inverse relationship between the culture of safety component score and the Serious Harm Index (odds ratio [OR] = 0.63, 95% confidence interval [CI] 0.42–0.95, P = 0.03). There was no association between the overall high-reliability score (OR = 0.91, 95% CI 0.78–1.05, P = 0.19), the Leadership component score (OR = 0.97, 95% CI 0.70–1.33, P = 0.84), or the robust process improvement (RPI) component score (OR = 0.75, 95% CI 0.41–1.28, P = 0.26) and the Serious Harm Index.

Conclusion:

The integration of high-reliability principles within healthcare may support improved patient safety in the hospital setting. Further research is needed to articulate the breadth and magnitude of the impact of integrating high-reliability principles into healthcare.
Healthcare Quality for Acute Illness during the COVID-19 Pandemic: A Multisite Qualitative Analysis
Authors: Leyenaar JoAnna K. , McDaniel Corrie E. , Arthur Kimberly C. , Stevens Cathryn A. , St Ivany Amanda R.
Published: September 2021

Introduction:

The coronavirus disease 2019 (COVID-19) pandemic incited substantial changes to acute care delivery, including the rapid scale-up of telehealth and numerous changes to in-person care. This study explored health system changes associated with the COVID-19 pandemic and their influences on pediatric acute care delivery and quality of care.

Methods:

We conducted 38 semistructured interviews May–November 2020 with families and clinicians from 3 US regions, eliciting their perspectives and experiences regarding changes to acute care delivery during the pandemic. Interviews were analyzed using a general inductive approach to identify relationships between clinical care infrastructure, care processes, and healthcare quality.

Results:

Emerging knowledge of COVID-19 epidemiology and associated restrictions influenced care-seeking behaviors and clinical infrastructure and processes. Infrastructure changes included the closure of some clinics, limited “sick visit” hours and locations, and increased resources for telehealth. Modified care processes included the assignment of clinicians to specific roles, limitations on sibling attendance, increased referrals to other clinics, and iterative development of procedures and protocols. Although intended to increase safety, these changes appear to have decreased access, timeliness, and equity of care. High-quality care was supported by telephone triage processes, in-person visits following initial assessments by telehealth, and identification of diagnoses and populations best-suited to telehealth versus in-person care.

Conclusions:

Changes in acute care delivery during the COVID-19 pandemic may have negatively impacted healthcare quality in some domains. Implementation of pediatric-specific guidelines and decision aids describing diagnoses, populations, and procedures best-suited to telehealth may improve the quality of acute care delivery.
Effects of pH, heat, and intestinal protease treatments on
antioxidant activity of antioxidant peptides derived from protein
hydrolysate of perilla seed meal
Authors: Kim Ja Min , Yoon Kyung Young
Published: September 2021

Perilla seed meal (PSM) is a by-product of perilla seed oil extraction and a good
source of bioactive peptides. In this study, the effects of heat, pH, and
intestinal protease treatments on the antioxidant activity and stability of two
antioxidant peptides (PAP1 and PAP2) were assessed and quantified; the stability
was evaluated by measuring the 1,1-diphenyl-2-picrylhydrazine (DPPH) radical
scavenging activity, 2,2'-azinobis-(3-ethylbenzothiazoline-6-sul- fonic acid
(ABTS) radical scavenging activity, and reducing power. The strength of the
antioxidant effects of PAP1 and PAP2 was found to be reasonably well preserved
relative to that of positive controls. Specifically, PAP1 and PAP2 maintained
their antioxidant activity or exhibited only slightly decreased activity after
heat treatment, with >76% activity retention. The antioxidant activities of PAP1
and PAP2 were lower than those of the controls under acidic and basic conditions
but remained above 70% at all pH values except pH 12. Additionally, the
antioxidant activity of both peptides remained above 66%, even after treatments
of pepsin, chymotrypsin, and trypsin. Thus, the results indicate that
antioxidant peptides from PSM protein hydrolysate are reasonably resistant to
heat, pH, and intestinal proteases. Furthermore, these results demonstrate that
antioxidant peptides derived from PSM hydrolysate exhibit high potential as
natural antioxidant peptides for food and/or nutraceutical applications.
Effect of organic acid and ultraviolet-C treatment on putrefactive
microorganisms and shelf-life of seasoned squid product
Authors: Xu Xiaotong , Lee Ji-Eun , Kim Eun-Jin , Jeong So-Mi , Ryu Si-Hyeong , Kang Woo-Sin , Kim Su-Ryong , Kim Han-Ho , Lee Ga-Hye , Ahn Dong-Hyun
Published: September 2021

The purpose of this study was to determine the effect of organic acid and
ultraviolet (UV)-C treatment on the storage stability and microbial quality of
seasoned squid product. The overall preference score was lower in the 1.5 M
citric acid group than in the untreated group. Since the pH of the citric
acid-treated product remained low during storage, its viable cell count reduced
21.34% compared with that of the untreated group. Compared with the untreated
group, the samples treated with lemon concentrate showed a remarkably lower
taste score but no significant difference in the scores for color, overall
smell, fishy smell, off-flavor, texture, and hardness. In addition, during
storage, the viable cell count in the lemon concentrate-treated group reduced to
7.42% compared to that of the untreated group. On day 50 of storage, the viable
cell count of the lemon concentrate-treated group reduced 28.16% more than that
of the untreated group. UV-C treatment of Bacillus subtilis and
Aspergillus ruber isolated from seasoned squid products
inhibited growth after irradiation for 35 and 90 minutes, respectively. These
findings indicate that UV-C, citric acid, and lemon concentrate treatment during
the product manufacturing process can improve the storage and quality of
seasoned squid products.
Quality and antioxidant properties of morning bread added with
sourdough according to the mixing ratios of sea buckthorn leaf
Authors: Park Min Gyu , Ji Hui Yeong , Joo Shin Youn
Published: September 2021

In this study, a natural fermentation starter formulation was developed for
functional bread products by substituting baker’s yeast with naturally fermented
sourdough added with sea buckthorn leaf (SBL). The quality and antioxidant
properties of morning bread (MB) with 0%, 10%, 20%, and 30% SBL added to
sourdough were investigated. The pH of MB dough decreased when the mixing ratio
(MR) of SBL was increased. The dough-raising power by incubation time (20-60
min) increased when the MR of SBL was increased. In the MB containing 30% SBL
sourdough, the height was lowest, and the baking loss rate was highest. The
specific volume of the control was the highest. The L value decreased, whereas
the b values increased, when MR of SBL was increased. Hardness was the highest
in MB containing 20% SBL sourdough. Total polyphenolic and total flavonoid
contents tended to increase as SBL increased. DPPH and ABTS+ radical
scavenging activities and reducing power of MB were also elevated due to
addition of MR of SBL. The sensory evaluation results revealed that MB
containing 20% SBL sourdough the highest overall preference. Collectively, these
results indicated that sourdough with 20% SBL was a very useful substitute for
baker’s yeast when making naturally fermented functional bread.
Changes in physicochemical and functional properties of
Opuntia humifusa by fermentation with Citrus
junos flesh and peel
Authors: Yong Sojin , Jeong Beom-Gyun , Shin Eui Cheol , Chun Jiyeon
Published: September 2021

In this study, Opuntia humifusa was fermented with
Citrus junos and its physicochemical and functional
properties were investigated. O. humifusa (Oh) was combined
with C. junos flesh (Oh-CF), peel (Oh-CP), or whole fruit
(Oh-CFP) and fermented at 30°C for 14 d. The number of lactic acid
bacteria rapidly increased to 7.1 log CFU/mL during the initial 10 d of
fermentation, resulting in decreases in pH and soluble sugar contents of Oh
samples. Total polyphenol content increased 4-5 folds in all samples during
fermentation. Isorhamnetin content was highest in Oh after 14 d of fermentation
whereas naringin and hesperidin contents were highest in Oh-CP after 6 d.
Antioxidant activity of samples increased approximately 3-4 folds during
fermentation. DPPH radical scavenging ability was highest in Oh-CFP after 10 d
of fermentation whereas reducing power was highest in Oh after 14 d.
α-Glucosidase inhibitory activity (GIA) of samples fermented with
C. junos was higher than that of acarbose (0.85
μg/mL), with the highest GIA observed for Oh-CFP fermented for 14 d (0.38
μg/mL). Favorable essential oils such as limonene, pinene, linalool,
terpinene and terpinolene were detected in samples with C.
junos. The addition of C. junos flesh and peel
would be useful for enhancement of physicochemical and functional properties
(antioxidant and GIA activities) of O. humifusa, which could be
effectively improved by modulating the fermentation period.
Analytical method validation of ellagic acid as an antioxidative marker compound of the Rubus occidentalis extract
Authors: Lee Jeong Ho , Jeong Kyoung Ok , Im So Yeon , Lee Seung Je
Published: September 2021

The content of ellagic acid obtained from the extracts of Rubus occidentalis (RC) and its antioxidant activity were measured to secure basic data for developing functional materials. The extract was prepared by boiling RC in water for 3 h at 90°C. The polyphenol content and 2,2'-azinbis-(3-ethyl-benzothiazoline-6-sulfonic acid) (ABTS) radical scavenging activity (IC50) of RC was 30.60±1.27 mg/g and 176±3.95 μg/mL, respectively. RC acid hydrolysate (RCH) was analyzed using HPLC and ellagic acid as a marker compound. HPLC was used to separate the content using the following experimental conditions. Gradient solvent made of 0.1% formic acid and acetonitrile/methanol (85:15 v/v) was used with elution solvent gradient. Separation was performed on a C18 MGII column (4.6×250 mm, 5 μm) and with a 254 nm PDA detector. Limit of detection (LOD), limit of quantification (LOQ), precision, accuracy, and recall rate were measured. Ellagic acid and RCH were separated from other substances with a consistent detection time and peak retention time. Ellagic acid and RCH were eluted as a single peak on the chromatogram at approximately about 17.9 min. The maximum absorbance of ellagic acid and RCH was consistent at 254 nm PDA spectrum. These results indicate that ellagic acid and RCH are similar and there are some specific differences. The correlation coefficient (R2) of the calibration curve showed a 0.9999 linearity, 0.1330 μg/mL LOD, and 0.4029 μg/mL LOQ. Inter-day precision, and intermediate precision were 12.95-13.48 mg/g (1.38-3.70% RSD) and 13.16-13.41 mg/g (1.19-2.51% RSD), respectively. The ellagic acid and RCH contents were 6.17±0.80 mg/g and 19.56±3.56 mg/g, respectively. The content of ellagic acid increased with increasing extraction and hydrolysis time. Our findings suggest that HPLC analysis could be used for validating ellagic acid as a marker compound of RC.
Production of D-fructose from starch by amylase and glucose
isomerase
Authors: Kim Sang Jin , Choi Ji In , Choi Min Su , Park Chang-Su
Published: September 2021

Two commercial enzymes, amylase and glucose isomerase, were applied in sequential
and simultaneous enzyme reactions to produce D-fructose from starch. 80 U/g
Fungamyl 800L, 35 U/mL glucose isomerase, and 20% of starch were the most
effective concentrations for this reaction. In the sequential enzyme reaction,
Fungamyl 800L maximally produced 56 g/L D-glucose from starch at pH 5.0 and
55°C for 2 h. Consequently, glucose isomerase was reacted with D-glucose
produced from starch by Fungamyl 800L at pH 6.0 and 55°C for 2 h. This
resulted in the production of 18.5 g/L D-fructose, however, the production of
D-fructose did not increase any more after a 2 h enzyme reaction. In the
simultaneous enzyme reaction, Fungamyl 800L and glucose isomerase were
simultaneously reacted with starch at pH 5.0 and 55°C. In the
simultaneous reaction, D-fructose production continued to increase as the
reaction time increased and finally 39 g/L D-fructose was produced from starch
after 18 h. Based on these results, the simultaneous enzyme reaction was found
to be more efficient than the sequential enzyme reaction with respect to the
production of D-fructose from starch using amylase and glucose isomerase.
Early-life respiratory viral infection results in impairment of adult lung function
Authors: Harb Laith H , Holt Patrick G , Strickland Deborah , Martino David , Larcombe Alexander N , Bosco Anthony
Published: September 2021

Respiratory viral infections in early-life are linked to the development of chronic lung diseases that persist into adulthood. The aim of this study was to develop a mouse model of early-life respiratory viral infection that would lead to impaired lung function in adulthood. BALB/c pups were infected at seven days of life with one of the following respiratory viruses: influenza A/Mem/1/71 “M71”, influenza A/Puerto Rico/8/34 “PR8” or attenuated mengovirus “Mengo”. Lung function and airways responsiveness (AHR) to methacholine were assessed seven weeks later, using the forced oscillation technique, and data were compared between male and female mice. PR8 infection was associated with significantly increased responsiveness to methacholine (for airway resistance, tissue damping, tissue elastance and hystersivity) for both sexes. M71 infection resulted in less severe responses especially in adult males. Early-life Mengo infection led to significantly higher responsiveness to MCh for males only (for airway resistance and tissue damping), suggesting sex dependant effects in lung function parameters measured. In summary, we have established a murine model where respiratory viral infection on day seven of life leads to AHR in adulthood. Importantly, the model recapitulates key variations in susceptibility related to sex and nature of viral pathogen that have previously been observed in human epidemiological studies. Our findings reveal new insights into the early origins of AHR and provide a tractable model system for future studies to unlock the mechanisms that determine pathogenesis.
Multiple stressors and recruitment failure of long-lived endangered freshwater mussels with a complex life cycle
Authors: Miura Kazuki , Ishiyama Nobuo , Negishi Junjiro N. , Ito Daisetsu , Kawajiri Keita , Izumi Hokuto , Inoue Takahiro , Nakaoka Masahiro , Nakamura Futoshi
Published: September 2021

Multiple stressors can interactively affect the population of organisms; however, the process by which they affect recruitment efficiency remains unclear for empirical populations. Recruitment efficiency can be regulated at multiple stages of life, particularly in organisms with complex life cycles. Understanding the interactive effects of multiple stressors on recruitment efficiency and determining the bottleneck life stages is imperative for species conservation.

The proportion of <20-year-old juveniles of the endangered freshwater pearl mussel Margaritifera togakushiensis, which has an obligate parasitic larval stage, was investigated in 24 rivers from eastern Hokkaido, northern Japan to reveal the influence of nutrients, fine sediment, and their combined effects on juvenile recruitment efficiency. The following indices for recruitment at adult, parasitic, and post-parasitic juvenile stages were obtained from 11 of these rivers: gravid female density, glochidia density (the number of glochidia infections per stream area), and juvenile survival rate. This study explored the bottleneck stages of recruitment efficiency and the interactive effects of the two stressors on these stages.

Twenty-four population status assessments determined that the proportion of juveniles ranged from 0.00 to 0.53, and juveniles were absent from four rivers. The results showed that the parasitic and post-parasitic juvenile stages were bottlenecks for recruitment efficiency. Juvenile survival rates had a more significant positive effect on recruitment efficiency in rivers with a high glochidia density. Juvenile survival rate was decreased by the synergistic interaction of nutrients and fine sediment, although factors limiting glochidia density were not found.

The nutrient concentration of rivers in the study region was well explained by the proportion of agricultural land cover and urban areas in the watersheds, but no relationship was detected between fine sediment abundance and land use.

This study suggests that nutrient management at a catchment scale can be effective for re-establishing the recruitment of M. togakushiensis, particularly in rivers with a high content of fine sediments. The results also emphasise the importance of considering both parasitic and post-parasitic juvenile stages of mussels to maximise the positive effects of stressor mitigation.
Probing nanomotion of single bacteria with graphene drums
Authors: Rosłoń I.E. , Japaridze A. , Steeneken P.G. , Dekker C. , Alijani F.
Published: September 2021

Motion is a key characteristic of every form of life1. Even at the microscale, it has been reported that colonies of bacteria can generate nanomotion on mechanical cantilevers2, but the origin of these nanoscale vibrations has remained unresolved3,4. Here, we present a novel technique using drums made of ultrathin bilayer graphene, where the nanomotion of single bacteria can be measured in its aqueous growth environment. A singleE. colicell is found to generate random oscillations with amplitudes of up to 60 nm, exerting forces of up to 6 nN to its environment. Using mutant strains, we are able to pinpoint the bacterial flagella as the main source of nanomotion. By real-time tracing of changes in nanomotion upon administering antibiotics, we demonstrate that graphene drums can perform antibiotic susceptibility testing with single-cell sensitivity. These findings deepen our understanding of processes underlying cellular dynamics, and pave the way towards high throughput and parallelized rapid screening of the effectiveness of antibiotics in bacterial infections with graphene devices.
Bioactive Hydrogel Microcapsules for Guiding Stem Cell Fate Decisions by Release and Reloading of Growth Factors
Authors: Gwon Kihak , Hong Hye Jin , Gonzalez-Suarez Alan M. , Slama Michael Q. , Choi Daheui , Hong Jinkee , Baskaran Harihara , Stybayeva Gulnaz , Peterson Quinn P. , Revzin Alexander
Published: September 2021

Human pluripotent stem cells (hPSC) hold considerable promise as a source of adult cells for treatment of diseases ranging from diabetes to liver failure. Some of the challenges that limit the clinical/translational impact of hPSCs are high cost and difficulty in scaling-up of existing differentiation protocols. In this paper, we sought to address these challenges through the development of bioactive microcapsules. A co-axial flow focusing microfluidic device was used to encapsulate hPSCs in microcapsules comprised of an aqueous core and a hydrogel shell. Importantly, the shell contained heparin moieties for growth factor (GF) binding and release. The aqueous core enabled rapid aggregation of hPSCs into 3D spheroids while the bioactive hydrogel shell was used to load inductive cues driving pluripotency maintenance and endodermal differentiation. Specifically, we demonstrated that one-time 1h long loading of pluripotency signals, fibroblast growth factor (FGF)-2 and transforming growth factor (TGF)-β1, into bioactive microcapsules was sufficient to induce and maintain pluripotency of hPSCs over the course of 5 days at levels similar to or better than a standard protocol with soluble GFs. Furthermore, stem cell-carrying microcapsules that previously contained pluripotency signals could be reloaded with an endodermal cue, Nodal, resulting in higher levels of endodermal markers compared to stem cells differentiated in a standard protocol. Overall, bioactive heparin-containing core-shell microcapsules decreased GF usage five-fold while improving stem cell phenotype and are well suited for 3D cultivation of hPSCs.
piRNAdb: A piwi-interacting RNA database
Authors: Piuco Ricardo , Galante Pedro A. F.
Published: September 2021

Motivation

Found in several metazoan species, piwi-interacting RNAs (piRNAs) regulate the expression of a wide variety of transposable elements and genes associated with cellular development, differentiation, and growth. Despite their importance, piRNAs are not well known and are still underexplored. To facilitate piRNA research, a comprehensive and easy-to-use piRNA database is still needed.

Results

Here, we present piRNAdb, an integrative and user-friendly database designed to encompass several aspects of piRNAs. We selected piRNAs from four reliable human RNA-sequencing datasets to start our database. After data processing, we displayed these sequences, their genomic location, clustering information, putative targets on known genes and transposable elements, as well as direct links to other databases. In this first release, piRNAdb catalogues 27,329 piRNAs, as well as 23,380 genes that are putative targets and 47,060 associated gene ontology terms, both of which are organized and linked to each respective piRNA. Finally, to improve information exchange and increase the confidence of sequences, a feedback system is provided to users of piRNAdb.

Conclusion

The inclusion of new features to facilitate piRNA analyses, data visualization, and integration is the major pillar of piRNAdb. Our main goal was to make this database an easy interface between the data and the user. We believe that this web tool achieves this objective by providing a streamlined and well-organized data repository for piRNAs and that it will be extremely useful to those already studying piRNAs and to the broader community.

Availability

piRNAdb is available freely and is compatible with smartphones and tablets: https://www.pirnadb.org/
Computationally-guided tuning of ligand sensitivity in a GPCR-based sensor
Authors: Keri Daniel , Cola Reto B. , Kagiampaki Zacharoula , Tommaso Patriarchi , Barth Patrick
Published: September 2021

Genetically-encoded fluorescent sensors for neuromodulators are increasingly used molecular tools in neuroscience. However, these protein-based biosensors are often limited by the sensitivity of the protein scaffold towards endogenous ligands. Here, we explored the possibility of applying computational design approaches for enhancing sensor sensitivity. Using the dopamine sensor dLight1 as proof of concept, we designed two variants that boost the sensor’s potency (EC50) for dopamine and norepinephrine by up to 5- and 15-fold, respectively. Interestingly, the largest effects were obtained through improved designed allosteric transmission in the transmembrane region of the sensor. Our approach should prove generally useful for enhancing sensing capabilities of a large variety of neuromodulator sensors.
Dynamics of fibril collagen remodeling by tumor cells using individual cell-based mathematical modeling
Authors: Poonja Sharan , Damaghi Mehdi , Rejniak Katarzyna A.
Published: September 2021

Many solid tumors are characterized by dense extracellular matrix (ECM) composed of various ECM fibril proteins that provide structural support and biological context for the residing cells. The growing tumor cell colonies are capable of remodeling the ECM structure in tumor immediate vicinity to form specific microenvironmental niches. The changes in fibril patterns of the collagen (one of the ECM proteins) surrounding the tumor can be visualized experimentally using both histology and fluorescent imaging. In particular, three diverse tumor associated collagen signatures (TACS) were identified and related to tumor behavior, such as benign growth or invasion. Here we will use an off-lattice hybrid agent-based model (MultiCell-LF) to identify the rules of cell-ECM interactions that guide the development of various patterns of alignment of the ECM fibrils.
Epidemiological rather than macro-economic factors correlate with socioeconomic inequalities in HIV testing in 16 sub-Saharan African countries
Authors: Ante-Testard Pearl Anne , Temime Laura , Jean Kévin
Published: September 2021

In order to reach the first 95 (i.e., 95% of people living with HIV having knowledge of their status) of the 2030 UNAIDS 95-95-95 targets, it is crucial to better understand the contextual or structural factors driving socioeconomic inequalities in HIV testing uptake. It is still unclear whether they are mostly influenced by epidemiological or by macro-economic factors. Here, to shed light on this issue, we measured and decomposed socioeconomic inequalities in HIV testing in sub-Saharan Africa in relation to contextual factors using a novel method, the Recentered Influence Function decomposition method. Indeed, we found that HIV testing uptake was more concentrated among the rich in 12 of 16 sub-Saharan African countries based on population-based surveys. The level of the HIV epidemic seems to drive the level of response of HIV testing programs, rather than the per capita Gross Domestic Product of a country (i.e., national indicator of economic development). Our results suggest that when responding to the HIV epidemic, there is a need to monitor and assess inequalities in addition to monitoring HIV incidence and prevalence.
Predicting Progression Free Survival after Systemic Therapy in Advanced Head and Neck Cancer: Bayesian regression and Model development
Authors: Barber Paul R , Flores-Borja Fabian , Alfano Giovanna , Ng Kenrick , Weitsman Gregory , Dolcetti Luigi , Mustapha Rami , Wong Felix , Vicencio Jose M , Galazi Myria , Opzoomer James W , Arnold James N , Kordasti Shahram , Doyle Jana , Greenberg Jon , Dillon Magnus T , Harrington Kevin J , Forster Martin D , Coolen Anthony C C , Ng Tony
Published: September 2021

Background

Advanced Head and Neck Squamous Cell Cancer (HNSCC) is associated with a poor prognosis, and biomarkers that predict response to treatment are highly desirable. The primary aim was to predict Progression Free Survival (PFS) with a multivariate risk prediction model.

Methods

Blood samples from 56 HNSCC patients were prospectively obtained within a Phase 2 clinical trial (NCT02633800), before and after the first treatment cycle of platinum-based chemotherapy, to identify biological covariates predictive of outcome. A total of 42 baseline covariates were derived pre-treatment, which were combined with 29 covariates after one cycle of treatment. These covariates were ranked and selected by Bayesian multivariate regression to form risk scores to predict PFS, producing “baseline” and “combined” risk prediction models respectively.

Results

The baseline model comprised of CD33+CD14+ monocytes, Double Negative B cells and age, in a weighted risk signature which predicted PFS with a concordance index (C-index) of 0.661. The combined model composed of baseline CD33+CD14+ monocytes, baseline Tregs, after-treatment changes in CD8 effector memory T cells, CD8 Central memory T cells and CD3 T Cells, along with the hypopharyngeal primary tumor subsite. This weighted risk signature exhibited an improved C-index of 0.757. There was concordance between levels of CD33+CD14+ myeloid cells in tumor tissue, as demonstrated by imaging mass cytometry, and peripheral blood in the same patients. This monocyte subpopulation also had univariate predictive value (log-rank p value = 0.03) but the C-index was inferior to the combined signature.

Conclusions

This immune-based combined multimodality signature, obtained through longitudinal peripheral blood monitoring, presents a novel means of predicting response early on during the treatment course.

Funding

Daiichi Sankyo Inc, Cancer Research UK, EU IMI2 IMMUCAN, UK Medical Research Council, European Research Council (335326), National Institute for Health Research and The Institute of Cancer Research.
Feasibility, Acceptability, and Barriers to Implementing Select Non-Pharmaceutical Interventions to Reduce the Transmission of Pandemic Influenza - United States, 2019
Authors: Ahmed Faruque , Qualls Noreen , Kowalczyk Shelly , Cunningham Suzanne Randolph , Zviedrite Nicole , Uzicanin Amra
Published: September 2021

Objective

To assess feasibility and acceptability of implementing non-pharmaceutical interventions (NPIs) reserved for influenza pandemics (voluntary home quarantine; use of face masks by ill persons; childcare facility closures; school closures; and social distancing at schools, workplaces, and mass gatherings), and the availability and usefulness of influenza surveillance data for triggering implementation of NPIs.

Methods

Public health officials in all 50 states, Washington, DC, and 8 territories, and a stratified, random sample of 822 local health departments (LHDs) were surveyed in 2019.

Results

The response rates for the states/territories and LHDs were 75% (44/59) and 25% (206/822), respectively. About two-thirds to three-fourths of the state/territorial respondents stated that the feasibility and acceptability of implementing the NPIs were high, except for K-12 school closures lasting up to 6 weeks or 6 months. The LHD respondents also indicated that feasibility and acceptability were lowest for prolonged school closures. Compared to LHD respondents in suburban or urban areas, those in rural areas expressed lower feasibility and acceptability. Availability of influenza surveillance data in near real-time was lowest for influenza-like illness and influenza cases in schools.

Conclusions

The findings can provide insights regarding the implementation of NPIs during the Corona Virus Disease 2019 (COVID-19) pandemic.
CAR T cell therapy drives endogenous locoregional T cell dynamics in a responding patient with glioblastoma
Authors: Jonsson Vanessa D. , Ng Rachel H. , Dullerud Natalie , Wong Robyn A. , Hibbard Jonathan , Wang Dongrui , Aguilar Brenda , Starr Renate , Weng Lihong , Alizadeh Darya , Forman Stephen J. , Badie Behnam , Brown Christine E.
Published: September 2021

CAR T cell therapy has transformed clinical care and management of patients with certain hematological cancers. However, it remains unclear whether the success of CAR T cell therapy relies solely on CAR T cell engagement with tumor antigen, or if it also requires the stimulation of an individual patient’s endogenous T cell response. Here, we performed combined analysis of longitudinal, single cell RNA and T cell receptor sequencing on glioblastoma tumors, peripheral blood (PB), and cerebrospinal fluid (CSF) from a patient with recurrent multifocal glioblastoma that underwent a remarkable response followed by recurrence on IL13RA2-targeted CAR T cell therapy (Brown et al. 2016). Single cell analysis of a tumor resected prior to CAR T cell therapy revealed the existence of an inflamed tumor microenvironment including a CD8+ cytotoxic, clonally expanded and antigen specific T cell population that disappeared in the recurrent setting. Longitudinal tracking of T cell receptors uncovered distinct T cell dynamics classes in the CSF during CAR T cell therapy. These included T cell clones with transient dynamics, representing intraventricular CAR T cell delivery and endogenous T cell recruitment from the PB into the CSF; and a group of T cells in the cerebrospinal fluid, that tracked with clonally expanded tumor resident T cells and whose dynamics contracted concomitantly with tumor volume. Our results suggest the existence of an endogenous T cell population that was invigorated by intraventricular CAR T cell infusions, and combined with the therapy to produce a complete response.
Mitochondrial stress-induced GDF15-GFRAL axis promotes anxiety-like behavior and CRH-dependent anorexia
Authors: Gil Carla Igual , Coull Bethany M. , Jonas Wenke , Lippert Rachel , Ost Mario , Klaus Susanne
Published: September 2021

Growth differentiation factor 15 (GDF15) is a stress-induced cytokine that modulates food intake and energy metabolism. Until now, most mechanistic studies on GDF15 rely on pharmacological interventions using exogenous GDF15, but little is known about its mode of action when induced both chronically and endogenously. Mitochondrial stress is one of the most described physiological conditions that induces GDF151, and therefore an important model to study the underlying mechanisms of endogenous GDF15’s action. Here, using a mouse model of mitochondrial dysfunction via elevated respiratory uncoupling in skeletal muscle, we show a circadian oscillation of muscle-derived GDF15 to promote a daytime-restricted anorexia without signs of nausea or reduced physical activity, contrary to findings using recombinant GDF152–5. We find that mitochondrial stress-induced GDF15 associates with increased anxiety and hypothalamic corticotropin releasing hormone (CRH) induction, without further activation of the hypothalamic-pituitary-adrenal (HPA) axis and corticosterone response. Strikingly, the daytime-restricted anorexia, lean phenotype, systemic shift in substrate metabolism and anxiety-like behavior are completely abolished in conditions of mitochondrial stress coupled with genetic ablation of the GDF15 receptor GDNF receptor alpha-like (GFRAL), which is predominantly expressed in the hindbrain. Finally, we demonstrate that stress-induced GDF15-GFRAL signaling is required for hypothalamic CRH induction to control diurnal food intake in a CRH-receptor 1 (CRHR1)-dependent manner. With this, we uncover for the first time a molecular target of the GDF15-GFRAL axis that links anxiolytic and anorectic behavior as downstream effects of the chronic activation of this pathway by mitochondrial stress.
DSS-induced inflammation in the colon drives a pro-inflammatory signature in the brain that is ameliorated by prophylactic treatment with the S100A9 inhibitor paquinimod
Authors: Talley Sarah , Valiauga Rasa , Anderson Lillian , Cannon Abigail R , Choudhry Mashkoor A , Campbell Edward M
Published: September 2021

Background: Inflammatory Bowel Disease (IBD) is established to drive pathological sequelae in organ systems outside the intestine, including the central nervous system (CNS). Many patients exhibit cognitive deficits, particularly during disease flare. The connection between colonic inflammation and neuroinflammation remains unclear and characterization of the neuroinflammatory phenotype in the brain during colitis is ill-defined. Methods: Transgenic mice expressing a bioluminescent reporter of active caspase-1 were treated with 2% Dextran Sodium Sulfate (DSS) for 7 days to induce acute colitis, and colonic, systemic and neuroinflammation were assessed. In some experiments, mice were prophylactically treated with paquinimod (ABR-215757) to inhibit S100A9 inflammatory signaling. As a positive control for peripheral-induced neuroinflammation, mice were injected with lipopolysaccharide (LPS). Colonic, systemic and brain inflammatory cytokines and chemokines were measured by cytokine bead array (CBA) and Proteome profiler mouse cytokine array. Bioluminescence was quantified in the brain and caspase activation was confirmed by immunoblot. Immune cell infiltration into the CNS was measured by flow cytometry, while light sheet microscopy was used to monitor changes in resident microglia localization in intact brains during DSS or LPS-induced neuroinflammation. RNA sequencing was performed to identify transcriptomic changes occurring in the CNS of DSS-treated mice. Expression of inflammatory biomarkers were quantified in the brain and serum by qRT-PCR, ELISA and WB. Results: DSS-treated mice exhibited clinical hallmarks of colitis, including weight loss, colonic shortening and inflammation in the colon. We also detected a significant increase in inflammatory cytokines in the serum and brain, as well as caspase and microglia activation in the brain of mice with ongoing colitis. RNA sequencing of brains isolated from DSS-treated mice revealed differential expression of genes involved in the regulation of inflammatory responses. This inflammatory phenotype was similar to the signature detected in LPS-treated mice, albeit less robust and transient, as inflammatory gene expression returned to baseline following cessation of DSS. Pharmacological inhibition of S100A9, one of the transcripts identified by RNA sequencing, attenuated colitis severity and systemic and neuroinflammation. Conclusions: Our findings suggest that local inflammation in the colon drives systemic inflammation and neuroinflammation, and this can be ameliorated by inhibition of the S100 alarmin, S100A9.
Literature-Based Discovery beyond the ABC paradigm: a contrastive approach
Authors: Moreau Erwan , Hardiman Orla , Heverin Mark , O’Sullivan Declan
Published: September 2021

Literature-Based Discovery (LBD) aims to help researchers to identify relations between concepts which are worthy of further investigation by text-mining the biomedical literature. The vast majority of the LBD research follows the ABC model: a relation (A,C) is a candidate for discovery if there is some intermediate concept B which is related to both A and C. The ABC model has been successful in applications where the search space is strongly constrained, but there is limited evidence about its usefulness when applied in a broader context.

Through a case study of 8 recent discoveries related to neurodegenerative diseases (NDs), we show the limitations of the ABC model in an open-ended context. The study emphasizes the impact of the choice of source data and extraction method on the resulting knowledge base: different “views” of the biomedical literature offer different levels of accuracy and coverage. We propose a novel contrastive approach which leverages these differences between “views” in order to target relations between concepts of interest. We explore various parameters and demonstrate the relevance of our approach through quantitative evaluation on the 8 target discoveries.

The source data used in this article are publicly available. The different parts of the software used to process the data are published under open-source license and provided with detailed instructions. The main code for this paper is available at https://github.com/erwanm/lbd-contrast (required dependencies are detailed in the documentation). A prototype of the system is also provided as an online exploration tool at brainmend.adaptcentre.ie.
Characterizing pupil dynamics coupling to brain state fluctuation based on lateral hypothalamic activity
Authors: Takahashi Kengo , Sobczak Filip , Pais-Roldán Patricia , Yu Xin
Published: September 2021

Pupil dynamics presents varied correlation features with brain activity under different vigilant levels. The modulation of brain state changes can arise from the lateral hypothalamus (LH), where diverse neuronal cell types contribute to arousal regulation in opposite directions via the anterior cingulate cortex (ACC). However, the relationship of the LH and pupil dynamics has seldom been investigated. Here, we performed local field potential (LFP) recordings at the LH and ACC, and the whole brain fMRI with simultaneous fiber photometry Ca2+ recording in the ACC, to evaluate their correlation with brain state-dependent pupil dynamics. Both LFP and functional MRI (fMRI) data showed opposite correlation features to pupil dynamics, demonstrating an LH activity-dependent manner. Our results demonstrate that the correlation of pupil dynamics with ACC LFP and whole-brain fMRI signals depends on LH activity, indicating a role of the latter in brain state regulation.
Enculturating a Community of Action (CoA): A qualitative study of health professions educators’ perspectives on teaching with Wikipedia
Authors: Martin Paolo C. , Maggio Lauren A. , Murray Heather , Willinsky John M.
Published: September 2021

Purpose

There is a growing desire for health professions educators to engage learners in more meaningful instruction. Many have tapped Wikipedia to offer an applied approach to engage learners, particularly as it relates to evidence-based medicine (EBM). However, little is known about the benefits and challenges of using Wikipedia as a pedagogical tool from the collective experience of educators who have sought to improve their instructional practice with it. This study aims to uncover and synthesize the perspectives of health professions education (HPE) instructors who have incorporated Wikipedia in their HPE courses.

Methods

Applying a constructivist approach, the authors conducted semi-structured interviews with 17 participating HPE instructors who had substantively integrated Wikipedia into their curriculum. Participants were interviewed about their experiences of integrating Wikipedia editing into their courses. Thematic analysis was conducted on resulting transcripts.

Results

Authors observed two broad themes among participants’ expressed benefits of teaching with Wikipedia: 1) provides a meaningful instructional alternative that also benefits society and develops learners’ information literacy and EBM skills, and 2) supports learners’ careers and professional identity formation. Identified challenges included: 1) high effort and time, 2) issues with sourcing references, and 3) challenging interactions with skeptics, editors, and students.

Discussion

Findings build on known benefits, such as providing a real-world collaborative project that contextualizes students’ learning experiences. They also echo known challenges, such as the resource-intensive nature of teaching with Wikipedia. At the same time, findings extend the current literature by revealing a potential opportunity to approach crowd-sourced information tools, like Wikipedia, as a vehicle to engage and enculturate HPE students within a situated learning context. These findings present implications for HPE programs considering implementing Wikipedia and faculty development needed to help instructors harness crowd-sourced information tools’ pedagogical opportunities as well as anticipate their challenges.