bluuebunny/crossref_metadata_2025_split huggingface dataset:
Synergistic effects of novel penicillin-binding protein 1A amino acid substitutions contribute to high-level amoxicillin resistance of
Helicobacter pylori
Authors: Cimuanga-Mukanya Alain , Tshibangu-Kabamba Evariste , Kisoko Patrick de Jesus Ngoma , Fauzia Kartika Afrida , Tshibangu Fabien Mbaya , Wola Antoine Tshimpi , Kashala Pascal Tshiamala , Ngoyi Dieudonné Mumba , Ahuka-Mundeke Steve , Revathi Gunturu , Disashi-Tumba Ghislain , Kido Yasutoshi , Matsumoto Takashi , Akada Junko , Yamaoka Yoshio 
Published: August 2024

ABSTRACT

The growing resistance to amoxicillin (AMX)—one of the main antibiotics used in
Helicobacter pylori
eradication therapy—is an increasing health concern. Several mutations of penicillin-binding protein 1A (PBP1A) are suspected of causing AMX resistance; however, only a limited set of these mutations have been experimentally explored. This study aimed to investigate four PBP1A mutations (i.e., T558S, N562H, T593A, and G595S) carried by strain KIN76, a high-level AMX-resistant clinical
H. pylori
isolate with an AMX minimal inhibition concentration (MIC) of 2 µg/mL. We transformed a recipient strain 26695 with the DNA containing one to four mutation allele combinations of the
pbp1
gene from strain KIN76. Transformants were subjected to genomic exploration and antimicrobial susceptibility testing. The resistance was transformable, and the presence of two to four PBP1A mutations (T558S and N562H, or T593A and G595S), rather than separate single mutations, was necessary to synergistically increase the AMX MIC up to 16-fold compared with the wild-type (WT) strain 26695. An AMX binding assay of PBP1A was performed using these strains, and binding was visualized by chasing Bocillin, a fluorescent penicillin analog. This revealed that all four-mutation allele-transformed strains exhibited decreased affinity to AMX on PBP1A than the WT. Protein structure modeling indicated that functional modifications occur as a result of these amino acid substitutions. This study highlights a new synergistic AMX resistance mechanism and establishes new markers of AMX resistance in
H. pylori
.

IMPORTANCE

The development of resistance to antibiotics, including amoxicillin, is hampering the eradication of
Helicobacter pylori
infection. The identification of mechanisms driving this resistance is crucial for the development of new therapeutic strategies. We have demonstrated
in vitro
the synergistic role of novel mutations in the
pbp1
gene of
H. pylori
that is suspected to drive amoxicillin resistance. Also deepening our understanding of amoxicillin resistance mechanisms, this study establishes new molecular markers of amoxicillin resistance that may be useful in molecular-based antibiotic susceptibility testing approaches for clinical practice or epidemiologic investigations.
‘Let me recommend… ’: use of digital nudges or recommender systems for overweight and obesity prevention—a scoping review protocol
Authors: Forberger Sarah , Reisch Lucia A , van Gorp Pieter , Stahl Christoph , Christianson Lara , Halimi Jihan , De Santis Karina Karolina , Malisoux Laurent , de-Magistris Tiziana , Bohn Torsten 
Published: August 2024

Introduction
Recommender systems, digital tools providing recommendations, and digital nudges increasingly affect our lives. The combination of digital nudges and recommender systems is very attractive for its application in preventing overweight and obesity. However, linking recommender systems with personalised digital nudges has a potential yet to be fully exploited. Therefore, this study aims to conduct a scoping review to identify which digital nudges or recommender systems or their combinations have been used in obesity prevention and to map these systems according to the target population, health behaviour, system classification (eg, mechanisms for developing recommendations, delivery channels, personalisation, interconnection, used combination), and system implementation.

Methods and analysis
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews guideline was used to inform protocol development. The eligibility criteria are based on the PCC framework (Population: any human; Concept: recommender systems or digital nudges; Context: obesity prevention). MEDLINE, PsycINFO, Web of Science, CINHAL, Scopus, ACM Digital Library and IEEE Xplore were searched until September 2023. Primary studies with any design published in peer-reviewed academic journals and peer-reviewed conference papers will be included. Data will be extracted into a pre-developed extraction sheet. Results will be synthesised descriptively and narratively.

Ethics and dissemination

No ethical approval is required for the scoping review, as data will be obtained from publicly available sources. The results of this scoping review will be published in a peer-reviewed journal, presented at conferences and used to inform the co-creation process and intervention adaptation in the context of a HealthyW8 project (
www.healthyw8.eu
).
Longitudinal multisite study of the chronobiological control of chronic pain: the CircaHealth CircaPain study protocol
Authors: Taccardi Doriana , Gowdy Hailey G M , Singer Norris Lesley , Daly-Cyr Jennifer , Zacharias Amanda M , Lu Zihang , Choinière Manon , Pagé M. Gabrielle , Ghasemlou Nader 
Published: August 2024

Introduction
One in five Canadians lives with chronic pain. Evidence shows that some individuals experience pain that fluctuates in intensity following a circadian (24-hour) rhythm. Endogenous molecular rhythms regulate the function of physiological processes that govern pain mechanisms. Addressing chronic pain rhythmicity on a molecular and biopsychosocial level can advance understanding of the disease and identify new treatment/management strategies. Our CircaHealth CircaPain study uses an online survey combined with ecological momentary assessments and biosample collection to investigate the circadian control of chronic pain and identify potential biomarkers. Our primary objective is to understand interindividual variability in pain rhythmicity, by collecting biopsychosocial measures. The secondary objective accounts for seasonal variability and the effect of latitude on rhythmicity.

Methods and analysis
Following completion of a baseline questionnaire, participants complete a series of electronic symptom-tracking diaries to rate their pain intensity, negative affect, fatigue and stress on a 0–10 scale at 8:00, 14:00 and 20:00 daily over 10 days. These measures are repeated at 6 and 12 months postenrolment to account for potential seasonal changes. We aim to recruit ≥2500 adults with chronic pain within Canada. Infrastructure is being developed to facilitate the collection of blood samples from subgroups of participants (~800) two times per day over 24–48 hours to identify rhythmic expression of circulating genes and/or proteins.

Ethics and dissemination
Ethical approval for this study was obtained by the Queen’s University Health Sciences and Affiliated Teaching Hospitals Research Ethics Board (File No. 6038114). Participants provide informed consent to participate, and their data will not be identifiable in any publication or report. Findings will be published in a relevant scientific journal and disseminated at scientific meetings and online webinars. We maintain a website to post updated resources and engage with the community. We employ knowledge mobilisation in the form of direct data sharing with participants.
Disappearing sperms and changing climate: correlating decreasing semen quality and population dynamics within the Sustainable Development Goals framework
Authors: Sengupta Pallav , Dutta Sulagna 
Published: August 2024

BackgroundRecent studies have reported a significant decline in human semen quality worldwide, raising concerns about climate change and its extensive effects on human health and biodiversity.MethodsThis article investigates the correlation between deteriorating semen quality and changing climate conditions, within the context of the United Nations Sustainable Development Goals (SDGs). It aims to explore the linkage between decreasing semen quality and climate change, and to understand its implications for population dynamics, reproductive health and sustainability.ResultsIntegrating findings within the SDGs framework, the study emphasises SDG 3 (good health and well-being), SDG 13 (climate action) and SDG 15 (life on land). A multidisciplinary approach, incorporating data from environmental science, epidemiology and demography, is used to statistically analyse global and regional trends in semen quality against climate variability indicators, such as temperature fluctuations and pollution levels. Preliminary findings indicate a strong correlation between adverse climate conditions and reduced semen quality, suggesting potential impacts on fertility rates and population health. The research highlights the importance of climate action (SDG 13) in protecting human reproductive health and ensuring population stability (SDG 3), while emphasising the interconnectedness of ecosystem health and human well-being (SDG 15).ConclusionThe article calls for integrated policy responses addressing climate change and reproductive health as interconnected challenges, advocating for enhanced cross-sectoral collaboration to achieve the SDGs through comprehensive strategies encompassing environmental protection, reproductive healthcare and population management for a sustainable future.
Precarious employment and the workplace transmission of COVID-19: evidence from workers’ compensation claims in Ontario, Canada
Authors: Shahidi Faraz V , Liao Qing , Landsman Victoria , Mustard Cameron A , Robson Lynda , Biswas Aviroop , Smith Peter M 
Published: August 2024

Objective
To examine the association between precarious employment and risk of work-related COVID-19 infection in Ontario, Canada.

Methods
We combined data from an administrative census of workers’ compensation claims with corresponding labour force statistics to estimate rates of work-related COVID-19 infection between April 2020 and April 2022. Precarious employment was imputed using a job exposure matrix capturing temporary employment, low wages, irregular hours, involuntary part-time employment and a multidimensional indicator of ‘low’, ‘medium’, ‘high’ and ‘very high’ overall exposure to precarious employment. We used negative binomial regression models to quantify associations between precarious employment and accepted compensation claims for COVID-19.

Results
We observed a monotonic association between precarious employment and work-related COVID-19 claims. Workers with ‘very high’ exposure to precarious employment presented a nearly fivefold claim risk in models controlling for age, sex and pandemic wave (rate ratio (RR): 4.90, 95% CI 4.07 to 5.89). Further controlling for occupational exposures (public facing work, working in close proximity to others, indoor work) somewhat attenuated observed associations. After accounting for these factors, workers with ‘very high’ exposure to precarious employment were still nearly four times as likely to file a successful claim for COVID-19 (RR: 3.78, 95% CI 3.28 to 4.36).

Conclusions
During the first 2 years of the pandemic, precariously employed workers were more likely to acquire a work-related COVID-19 infection resulting in a successful lost-time compensation claim. Strategies aiming to promote an equitable and sustained recovery from the pandemic should consider and address the notable risks associated with precarious employment.
An innovative single-cell approach for phenotyping and functional genotyping of CAR NK cells
Authors: Sullivan Matthew Ryan , Finocchiaro Michael , Yang Yichao , Thomas Judene , Ali Alaa , Kaplan Isabel , Abdulhamid Yasmin , Bobilev Eden , Sheffer Michal , Romee Rizwan , Konry Tania 
Published: August 2024

BackgroundTo accelerate the translation of novel immunotherapeutic treatment approaches, the development of analytic methods to assess their efficacy at early in vitro stages is necessary. Using a droplet-based microfluidic platform, we have established a method for multiparameter quantifiable phenotypic and genomic observations of immunotherapies. Chimeric antigen receptor (CAR) natural killer (NK) cells are of increased interest in the current immunotherapy landscape and thus provide an optimal model for evaluating our novel methodology.MethodsFor this approach, NK cells transduced with a CD19 CAR were compared with non-transduced NK cells in their ability to kill a lymphoma cell line. Using our microfluidic platform, we were able to quantify the increase in cytotoxicity and synaptic contact formation of CAR NK cells over non-transduced NK cells. We then optimized our droplet sorter and successfully used it to separate NK cells based on target cell killing to perform transcriptomic analyses.ResultsOur data revealed expected improvement in cytotoxicity with the CD19 CAR but more importantly, provided unique insights into the factors involved in the cytotoxic mechanisms of CAR NK cells. This demonstrates a novel, improved system for accelerating the pre-clinical screening of future immunotherapy treatments.ConclusionsThis study provides a new potential approach for enhanced early screening of immunotherapies to improve their development, with a highly relevant cell model to demonstrate. Additionally, our validation studies provided some potential insights into transcriptomic determinants influencing CAR NK cytotoxicity.
Role of emotions in change and change management in an emergency department: a qualitative study
Authors: Ratnapalan Savithiri , Lang Daniel , Janzen Katharine , Muzzin Linda 
Published: August 2024

BackgroundChanges in emergency departments are frequently implemented to improve efficiency and reduce costs. However, staff acceptance and adoption are crucial for the intended success of changes.ObjectivesThis study explored staff perceptions of factors influencing the implementation of changes and any common themes linking changes and factors influencing changes in an emergency department at a university teaching hospital in the UK.MethodsWe used constructivist grounded theory methodology to perform a secondary analysis of 41 interview transcripts of physicians, nurses, support workers and managers involved in paediatric emergency care.ResultsParticipants identified leadership, communication and education as factors impacting change management. They described many emotions associated with changes and with communication, leadership and education or the lack of any of them during changes. Both positive and negative emotions sometimes coexisted at individual, team or organisational levels. Negative emotions were due to real-life challenges and concern over compromised patient care. Professional values dictated the actions or inactions that transpired either because of these emotions or despite these emotions in health professionals.ConclusionsEmotions to change should be acknowledged and addressed by credible leadership clear communication and education to improve the change process, its success and ultimately, patient care.
Does exercise modality and posture influence cerebrovascular and cardiovascular systems similarly?
Authors: Burkart Joshua J. , Johnson Nathan E. , Burma Joel S. , Neill Matthew G. , Smirl Jonathan D. 
Published: August 2024

Cerebral hemodynamics have been quantified during exercise via transcranial Doppler ultrasound, as it has high-sensitivity to movement artifacts and displays temporal superiority. Currently, limited research exists regarding how different exercise modalities and postural changes impact the cerebrovasculature across the cardiac cycle. Ten participants (4 females and 6 males) ages 20–29 completed three exercise tests (treadmill, supine, and upright cycling) to volitional fatigue. Physiological data collected included middle cerebral artery velocity (MCAv), blood pressure (BP), heart rate, and respiratory parameters. Normalized data were analyzed for variance and effect sizes were calculated to examine differences between physiological measures across the three exercise modalities. Systolic MCAv was greater during treadmill compared to supine and upright cycling ( p < 0.001, (large) effect size), and greater during upright versus supine cycling ( p < 0.017, (large)). Diastolic MCAv was lower during treadmill versus cycling exercise only at 60% maximal effort ( p < 0.005, (moderate)) and no differences were observed between upright and supine cycling. No main effect was found for mean and diastolic BP ( p > 0.05, (negligible)). Systolic BP was lower during treadmill versus supine cycling at 40% and 60% intensity ( p < 0.05, (moderate–large)) and greater during supine versus upright at only 60% intensity ( p < 0.003, (moderate)). The above differences were not explained by partial pressure of end-tidal carbon dioxide levels (main effect: p = 0.432) . The current study demonstrates the cerebrovascular and cardiovascular systems respond heterogeneously to different exercise modalities and aspects of the cardiac cycle. As physiological data were largely similar between tests, differences associated with posture and modality are likely contributors.
Diminishing productivity and hyperstable harvest in northern Wisconsin walleye fisheries
Authors: Mrnak Joseph T. , Embke H.S. , Wilkinson M.V. , Shaw S.L. , Vander Zanden M.J. , Sass G.G. 
Published: August 2024

Managing fisheries in a changing socio-ecological environment may require holistic approaches for identifying and adapting to novel ecosystem dynamics. Using 32 years of Ceded Territory of Wisconsin (CTWI) walleye ( Sander vitreus) data, we estimated production ( P), biomass ( B), biomass turnover ( P/B), yield ( Y), and yield over production ( Y/P) and tested for hyperstability in walleye yield. Most CTWI walleye populations showed low P and B, and Y/P < 1 . Yet, production overharvest ( Y/P > 1) was prevalent among Wisconsin walleye recruitment-based management approaches (natural recruitment (NR), sustained only by stocking, combination). Production, B, and P/B have declined in NR populations, while Y and Y/P have remained constant. Walleye Y was hyperstable along a production gradient among all management approaches and fishery types (i.e., angling only, angling/tribal harvest combined). Diminishing productivity and hyperstable yield may be jointly contributing to observed walleye declines. We classified lakes into management groups of low, moderate, or high vulnerability to harvest based on Y/P and P/B dynamics and identify that harvest may benefit from declines to maintain or increase the adaptive capacity of CTWI walleye.
Gravity’s rainbow effects on higher curvature modification of $$R^{2}$$ inflation
Authors: Yuennan Jureeporn , Channuie Phongpichit , Momeni Davood 
Published: August 2024

AbstractIn this work, we study several extensions of the higher curvature modification of $$R^{2}$$

R
2

inflation in the context of gravity’s rainbow. We modify the $$(R+R^{2})$$

(
R
+

R
2

)

model by adding an $$f_{1}R^3$$

f
1

R
3

-term, an $$f_{2}R^4$$

f
2

R
4

-term, and an $$f_{3}R^{3/2}$$

f
3

R

3
/
2

-term to the original model. We calculate the inflationary observables and confront them using the latest observational bounds from Planck 2018 data. We assume the rainbow function of the form $${\tilde{f}}=1+\left( \frac{H}{M}\right) ^{\lambda }$$

f
~

=
1
+

H
M

λ

with $$\lambda $$
λ
being a rainbow parameter and M a mass-dimensional parameter. We demonstrate that the power spectrum of curvature perturbation relies on the dimensionless coefficient $$f_{i},\,i=1,2,3$$

f
i

,

i
=
1
,
2
,
3

, a rainbow parameter $$\lambda $$
λ
and a ratio H/M. Likewise, the scalar spectral index $$n_s$$

n
s

is affected by both $$f_{i}$$

f
i

and the rainbow parameter. Moreover, the tensor-to-scalar ratio r is solely determined by the rainbow parameter. Interestingly, by ensuring that $$n_s$$

n
s

aligns with the Planck collaboration’s findings at the $$1\sigma $$

1
σ

confidence level, the tensor-to-scalar ratio could reach up to $$r\sim 0.01$$

r
∼
0.01

, which is possibly measurable for detection in forthcoming Stage IV CMB ground experiments and is certainly feasible for future dedicated space missions.
Elacestrant in ER+, HER2− Metastatic Breast Cancer with ESR1-Mutated Tumors: Subgroup Analyses from the Phase III EMERALD Trial by Prior Duration of Endocrine Therapy plus CDK4/6 Inhibitor and in Clinical Subgroups
Authors: Bardia Aditya , Cortés Javier , Bidard François-Clément , Neven Patrick , Garcia-Sáenz José , Aftimos Phillipe , O’Shaughnessy Joyce , Lu Janice , Tonini Giulia , Scartoni Simona , Paoli Alessandro , Binaschi Monica , Wasserman Tomer , Kaklamani Virginia 
Published: August 2024

Abstract

Purpose:
Elacestrant significantly prolonged progression-free survival (PFS) with manageable safety versus standard-of-care (SOC) endocrine therapy (ET) in patients with estrogen receptor–positive (ER+), HER2− metastatic breast cancer and tumors harboring estrogen receptor 1 (ESR1) mutation following ET plus a cyclin-dependent kinase 4/6 inhibitor (ET+CDK4/6i). In patients with ESR1-mutated tumors, we evaluated the efficacy and safety of elacestrant versus SOC based on prior ET+CDK4/6i duration and in clinical subgroups with prior ET+CDK4/6i ≥12 months.

Patients and Methods:
EMERALD, an open-label phase III trial, randomly assigned patients with ER+, HER2− metastatic breast cancer who had received 1–2 prior lines of ET, mandatory CDK4/6i, and ≤1 chemotherapy to elacestrant (345 mg daily) or SOC (aromatase inhibitor or fulvestrant). PFS was assessed across subgroups in post hoc exploratory analyses without adjustment for multiple testing.

Results:
In patients with ESR1-mutated tumors and prior ET+CDK4/6i ≥12 months, the median PFS for elacestrant versus SOC was 8.6 versus 1.9 months (HR, 0.41; 95% confidence interval, 0.26–0.63). In this population, the median PFS (in months) for elacestrant versus SOC was 9.1 versus 1.9 (bone metastases), 7.3 versus 1.9 (liver and/or lung metastases), 9.0 versus 1.9 (&lt;3 metastatic sites), 10.8 versus 1.8 (≥3 metastatic sites), 5.5 versus 1.9 (PIK3 catalytic subunit α mutation), 8.6 versus 1.9 (tumor protein p53 gene mutation), 9.0 versus 1.9 (HER2-low), 9.0 versus 1.9 (ESR1D538G-mutated tumors), and 9.0 versus 1.9 (ESR1Y537S/N-mutated tumors). Subgroup safety was consistent with the overall population.

Conclusions:
The duration of prior ET+CDK4/6i ≥12 months in metastatic breast cancer was associated with a clinically meaningful improvement in PFS for elacestrant compared with SOC and was consistent across all subgroups evaluated in patients with ER+, HER2−, ESR1-mutated tumors.