bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinicians’ experiences of obtaining informed consent for research and treatment: a nested qualitative study from Pakistan
Authors: Memon Rakhshi , Asif Muqaddas , Shah Bushra Ali , Kiran Tayyeba , Khoso Ameer B , Tofique Sehrish , Miah Jahanara , Ahmad Ayesha , Chaudhry Imran , Chaudhry Nasim , Husain Nusrat , Edwards Sarah J L 
Published: November 2024

Abstract
Background
Informed consent is considered to be the standard method for respecting the autonomy of individual participants in research and practices and is thought to be based on several conditions: (1) providing information on the purpose of the research or a specific treatment, what it will entail, (2) the participants being mentally competent to understand the information and weigh it in the balance, and (3) the participants to be free from coercion. While there are studies of informed consent in other countries, especially Low and Middle Income Countries (LMICs), this study explored the experiences of clinicians regarding the process of obtaining informed consent to participate in a Randomised Controlled Trial (RCT) in particular and treatment in general in healthcare settings, both general and mental health, specifically focusing on the tension between individualistic concept of autonomy and collectivist values in cultures such as Pakistan.

Methods
Qualitative interviews with 20 clinicians from healthcare settings in Pakistan who also served as recruiters in a suicide prevention RCT in Pakistan. The interviews were guided by semi-structured topic guide. All interviews were audio-recorded and transcribed verbatim.

Results
The interviews revealed that shared decision making was more morally important than individual autonomy, the role of the family played a dominant part in the consent-taking procedure, the decision of the elder and/or family patriarch took prominence, and that clinician-researchers encountered significant challenges in consent process in Pakistan, while recruiting patients into the trial as well as during routine treatment processes in healthcare settings. Four distinct themes emerged which were (1) Family deciding for patients, (2) Benefits of involving family in consent process, (3) Gender disparity in consent process, (4) Challenges experienced by clinician-researchers during consent process in Pakistan.

Conclusions
The concept of consent is generally considered important in many cultures, however, there are two strands of understanding. There seems to be consensus that participant agreement is necessary to protect the participant but with regards to autonomy there are significant cultural differences whether it is the right for autonomy of the individual (individualistic concept) or family, community, or expert authority in other cultures. In Pakistan clinician-researchers sometimes preferred one approach and sometimes the other as they appreciated the interests of the patient to be.
Efficacy of attractive targeted sugar bait stations against malaria in Western Province Zambia: epidemiological findings from a two-arm cluster randomized phase III trial
Authors: Ashton Ruth A. , Saili Kochelani , Chishya Chama , Banda Yikona Handrinah , Arnzen Annie , Orange Erica , Chitoshi Chanda , Chulu John , Tobolo Titus , Ndalama Frank , Kyomuhangi Irene , Ngulube Willy , Moonga Hawela , Chirwa Jacob , Slutsker Laurence , Wagman Joseph , Chanda Javan , Miller John , Silumbe Kafula , Hamainza Busiku , Eisele Thomas P. , Yukich Joshua , Littrell Megan 
Published: November 2024

Abstract
Background
Attractive targeted sugar bait (ATSB) stations containing bait (to attract) and ingestion toxicant (to kill) sugar-foraging mosquitoes are hypothesized to reduce malaria transmission by shortening the lifespan of Anopheles vectors.

Methods
A two-arm cluster-randomized controlled trial (cRCT) was conducted in Western Province Zambia. Seventy clusters of 250–350 households were assigned (1:1) by restricted randomization to an intervention arm (ATSB) or control arm (no ATSB) in the context of standard of care vector control (insecticide-treated nets and/or indoor residual spraying). Two ATSB stations (Westham Sarabi, 0.11% dinotefuran w/w) were maintained on exterior walls of eligible household structures for a 7-month deployment period (December-June) during the high malaria transmission season. The primary outcome was clinical malaria incidence among two consecutive seasonal cohorts of children aged 1–14 years, followed-up monthly from January-June in 2022 and 2023. Secondary outcome was Plasmodium falciparum prevalence among individuals aged over six months. Analysis compared clinical malaria incidence and prevalence between arms among the intention-to-treat population.

Results
ATSB coverage, assessed by cross-sectional survey, was 98.3% in March–April 2022 and 89.5% in March–April 2023. 4494 children contributed any follow-up time to the cohort, with 2313 incident malaria cases in the intervention arm (1.28 per child per six-month transmission season), and 2449 in the control arm (1.38 per child-season). The incidence rate ratio between the two arms was 0.91 (95% CI 0.72–1.15, p = 0.42). 2536 individuals participated in cross-sectional surveys, with prevalence of P. falciparum 50.7% in the intervention arm and 53.5% in the control arm. The odds ratio between the two arms was 0.89 (95% CI 0.66–1.18, p = 0.42). Secondary covariable-adjusted and subgroup analyses did not substantially alter the findings. No serious adverse events associated with the intervention were reported.

Conclusions
Two ATSB stations deployed per eligible structure for two consecutive transmission seasons did not result in a statistically significant reduction in clinical malaria incidence among children aged 1–14 years or in P. falciparum prevalence in rural western Zambia. Further studies are needed to assess the efficacy of ATSB stations in different settings and with different deployment strategies.

Trial registration
The trial is registered with Clinicaltrials.gov (NCT04800055).
Unpacking occupational and sex divides to understand the moderate progress in life expectancy in recent years (France, 2010’s)
Authors: Merville Ophélie , Bonnet Florian , Launoy Guy , Camarda Carlo Giovanni , Cambois Emmanuelle 
Published: November 2024

Abstract
Purpose
The growth in life expectancy (LE) slows down recently in several high-income countries. Among the underlying dynamics, uneven progress in LE across social groups has been pointed out. However, these dynamics has not been extensively studied, partly due to data limitations. In this paper, we explore this area for the 2010 decade using recent French data.

Methods
We utilize the recent change in French census mortality follow-up data (EDP) and apply P-spline models to estimate LEs across five occupational classes (OCs) and indicators of lifespan heterogeneity (edagger) within these OCs, for seven triennial periods (2011-2013 to 2017-2019).

Results
First, we found a similar ranking of OCs along the LE gradient over time and across sexes, from manual workers to higher-level OCs. Noteworthy, the lowest LE in women overlaps with the highest one in men drawing a sex-OC gradient. Second, we observe varying progress of LEs. In women, LE increases in higher-level OCs meanwhile it levels off in manual workers, so that the OCs gap widens (up to 3.4 years in 2017-2019). Conversely, in men LE stalls in higher-level OCs and increases in manual workers so that the gap, which is much larger than in women (+5.7 years in 2017-2019), is tending to narrow. Finally, the lifespan homogenizes in OCs only when LE is low.

Conclusion
Overall, the limited LE progress in France results from LE stalling in the middle of the sex-OC gradient, though LE increases at both ends. At the lower end, LE progress and lifespan homogenization suggest that laggards benefit recently improvements achieved earlier in other OCs. At the upper end, LE progress may come from a vanguard group within higher-lever OC, benefiting new sources of improvements. These findings underscore the need for further research to explore the diverse mortality dynamics coexisting in the current health landscape.
Nanotechnology in healthcare, and its safety and environmental risks
Authors: Ma Xiaohan , Tian Yaxin , Yang Ren , Wang Haowei , Allahou Latifa W. , Chang Jinke , Williams Gareth , Knowles Jonathan C. , Poma Alessandro 
Published: November 2024

AbstractNanotechnology holds immense promise in revolutionising healthcare, offering unprecedented opportunities in diagnostics, drug delivery, cancer therapy, and combating infectious diseases. This review explores the multifaceted landscape of nanotechnology in healthcare while addressing the critical aspects of safety and environmental risks associated with its widespread application. Beginning with an introduction to the integration of nanotechnology in healthcare, we first delved into its categorisation and various materials employed, setting the stage for a comprehensive understanding of its potential. We then proceeded to elucidate the diverse healthcare applications of nanotechnology, spanning medical diagnostics, tissue engineering, targeted drug delivery, gene delivery, cancer therapy, and the development of antimicrobial agents. The discussion extended to the current situation surrounding the clinical translation and commercialisation of these cutting-edge technologies, focusing on the nanotechnology-based healthcare products that have been approved globally to date. We also discussed the safety considerations of nanomaterials, both in terms of human health and environmental impact. We presented the in vivo health risks associated with nanomaterial exposure, in relation with transport mechanisms, oxidative stress, and physical interactions. Moreover, we highlighted the environmental risks, acknowledging the potential implications on ecosystems and biodiversity. Lastly, we strived to offer insights into the current regulatory landscape governing nanotechnology in healthcare across different regions globally. By synthesising these diverse perspectives, we underscore the imperative of balancing innovation with safety and environmental stewardship, while charting a path forward for the responsible integration of nanotechnology in healthcare.
Graphical abstract
Depression in patients with chronic otolaryngology symptoms – A vicious cycle
Authors: Khadilkar Meera Niranjan , K. Keshava Pai , Rai Thripthi , Shenoy Vijendra , Dosemane Deviprasad 
Published: November 2024

Abstract
Background
Depression is a common comorbidity among individuals with otolaryngologic disorders, particularly those with longstanding conditions. This study aims at analysing the sociodemographic profile of depressive disorders in patients with chronic otolaryngology symptoms or conditions, and the correlation with PHQ-9 score.

Methods
A cross-sectional study was conducted on a hundred patients presenting to the outpatient department with chronic otolaryngology symptoms or conditions. They were requested to fill in the PHQ-9 questionnaire, containing questions based on the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) for major depressive disorder (MDD).

Results
Median age was 39, male: female ratio was 1.17. Nasal obstruction (29%), ear discharge (25%), and headache (17%) were the common presenting complaints. Mean and median PHQ-9 scores were 5.03 and 4 respectively. Seven patients (7%) had MDD, while eleven (11%) had other depressive disorder; 9% of cases were found to have no significant otolaryngologic problem despite presenting with symptoms, two of which were found to have depressive disorder. Thirty-five (35%) and thirty-six (36%) patients had minimal and mild depressive symptoms respectively, while one (1%) had severe depressive symptoms. Statistical significance was noted for the duration of symptoms (p-value 0.005); high statistical significance was found for occupation and otolaryngology diagnosis (p-value < 0.001 each). PHQ-9 score showed statistical significance in comparison with gender and duration of symptoms (p-value 0.046 and 0.005 respectively). Correlation of severity of depressive disorder revealed statistical significance with gender (p-value 0.049) and high statistical significance with duration of symptoms (p-value < 0.001).

Conclusion
Chronic otolaryngology conditions are associated with significant morbidity, attributable to longstanding disturbing symptoms and prolonged treatment protocols, leading to depression. Nevertheless, depression in chronic otolaryngology disorders may aggravate or overlap the clinical symptoms or may go undetected. Hence it may be worthwhile to evaluate for depressive disorders in chronic patients presenting to otolaryngology.
Characterization of exosome-mediated propagation of systemic inflammatory responses into the central nervous system
Authors: Kodali Mahesh Chandra , Salim Chinnu , Ismael Saifudeen , Lebovitz Sarah Grace , Lin Geng , Liao Francesca-Fang 
Published: November 2024

AbstractThe mechanisms through which systemic inflammation exerts its effect on the central nervous system (CNS) are still not completely understood. Exosomes are small (30 to 100 nm) membrane-bound extracellular vesicles released by most of the mammalian cells. Exosomes play a vital role in cell-to-cell communication. This includes regulation of inflammatory responses by shuttling mRNAs, miRNAs, and cytokines, both locally and systemically to the neighboring as well as distant cells to further modulate the transcriptional and/or translational states and affect the functional phenotype of those cells that have taken up these exosomes. The role of circulating blood exosomes leading to neuroinflammation during systemic inflammatory conditions was hereby characterized. Serum-derived exosomes from LPS-challenged mice (SDEL) were freshly isolated from the sera of the mice that were earlier treated with LPS and used to study the effects on neuroinflammation. Exosomes isolated from the sera of the mice injected with saline were used as a control. In-vitro studies showed that the SDEL upregulate pro-inflammatory cytokine gene expression in the murine cell lines of microglia (BV-2), astrocytes (C8-D1A), and cerebral microvascular endothelial cells (bEnd.3). To further study their effects in-vivo, SDEL were intravenously injected into normal adult mice. Elevated mRNA expression of pro-inflammatory cytokines was observed in the brains of SDEL recipient mice. Proteomic analysis of the SDEL confirmed the increased expression of inflammatory cytokines in them. Together, these results demonstrate and strengthen the novel role of peripheral circulating exosomes in causing neuroinflammation during systemic inflammatory conditions.
Exposure to air pollutants and breast cancer risk: mediating effects of metabolic health biomarkers in a nested case–control study within the E3N-Generations cohort
Authors: Mercoeur Benoît , Fervers Béatrice , Coudon Thomas , Noh Hwayoung , Giampiccolo Camille , Grassot Lény , Faure Elodie , Couvidat Florian , Severi Gianluca , Mancini Francesca Romana , Roy Pascal , Praud Delphine , Amadou Amina 
Published: November 2024

Abstract
Background
Growing epidemiological evidence suggests an association between exposure to air pollutants and breast cancer. Yet, the underlying mechanisms remain poorly understood. This study explored the mediating role of thirteen metabolic health biomarkers in the relationship between exposure to three air pollutants, i.e. nitrogen dioxide (NO2), polychlorinated biphenyls 153 (PCB153), and benzo[a]pyrene (BaP), and breast cancer risk.

Methods
We used data from a nested case–control study within the French national prospective E3N-Generations cohort, involving 523 breast cancer cases and 523 matched controls. The four-way decomposition mediation of total effects for thirteen biomarkers was applied to estimate interaction and mediation effects (controlled direct, reference interaction, mediated interaction, and pure indirect effects).

Results
The analyses indicated a significant increase in breast cancer risk associated with BaP exposure (odds ratio (OR)Q4 vs Q1 = 2.32, 95% confidence intervals (CI): 1.00–5.37). PCB153 exposure showed a positive association only in the third quartile (ORQ3 vs Q1 = 2.25, CI 1.13–4.57), but it appeared to be non-significant in the highest quartile (ORQ4 vs Q1 = 2.07, CI 0.93–4.61). No association was observed between NO2 exposure and breast cancer risk. Estradiol was associated with an increased risk of breast cancer (OR per one standard deviation (SD) increment = 1.22, CI 1.05–1.42), while thyroid-stimulating hormone was inversely related to breast cancer risk (OR per 1SD increase = 0.87, CI 0.75–1.00). We observed a suggestive mediated effect of the association between the three pollutants and breast cancer risk, through albumin, high-density lipoproteins cholesterol, low-density lipoprotein cholesterol, parathormone, and estradiol.

Conclusion
Although limited by a lack of statistical power, this study provides relevant insights into the potential mediating role of certain biomarkers in the association between air pollutant exposure and breast cancer risk, highlighting the need for further in-depth studies in large populations.
VI-VS: calibrated identification of feature dependencies in single-cell multiomics
Authors: Boyeau Pierre , Bates Stephen , Ergen Can , Jordan Michael I. , Yosef Nir 
Published: November 2024

AbstractUnveiling functional relationships between various molecular cell phenotypes from data using machine learning models is a key promise of multiomics. Existing methods either use flexible but hard-to-interpret models or simpler, misspecified models. (Variational Inference for Variable Selection) balances flexibility and interpretability to identify relevant feature relationships in multiomic data. It uses deep generative models to identify conditionally dependent features, with false discovery rate control. is available as an open-source Python package, providing a robust solution to identify features more likely representing genuine causal relationships.
Estimated diagnostic performance of prostate MRI performed with clinical suspicion of prostate cancer
Authors: Nakai Hirotsugu , Takahashi Hiroaki , LeGout Jordan D. , Kawashima Akira , Froemming Adam T. , Lomas Derek J. , Humphreys Mitchell R. , Dora Chandler , Takahashi Naoki 
Published: November 2024

Abstract
Purpose
To assess the diagnostic performance of prostate MRI by estimating the proportion of clinically significant prostate cancer (csPCa) in patients without prostate pathology.

Materials and methods
This three-center retrospective study included prostate MRI examinations performed for clinical suspicion of csPCa (Grade group ≥ 2) between 2018 and 2022. Examinations were divided into two groups: pathological diagnosis within 1 year after the MRI (post-MRI pathology) is present and absent. Risk prediction models were developed using the extracted eleven common predictive variables from the patients with post-MRI pathology. Then, the csPCa proportion in the patients without post-MRI pathology was estimated by applying the model. The area under the receiver operating characteristic curve (AUC), sensitivity, specificity, and positive and negative predictive values (PPV/NPV) of prostate MRI in diagnosing csPCa were subsequently calculated for patients with and without post-MRI prostate pathology (estimated statistics) with a positive threshold of PI-RADS ≥ 3.

Results
Of 12,191 examinations enrolled (mean age, 65.7 years ± 8.4 [standard deviation]), PI-RADS 1–2 was most frequently assigned (55.4%) with the lowest pathological confirmation rate of 14.0–18.2%. Post-MRI prostate pathology was found in 5670 (46.5%) examinations. The estimated csPCa proportions across facilities were 12.6–15.3%, 18.4–31.4%, 45.7–69.9%, and 75.4–88.3% in PI-RADS scores of 1–2, 3, 4, and 5, respectively. The estimated (observed) performance statistics were as follows: AUC, 0.78–0.81 (0.76–0.79); sensitivity, 76.6–77.3%; specificity, 67.5–78.6%; PPV, 49.8–66.6% (52.0–67.7%); and NPV, 84.4–87.2% (82.4–86.6%).

Conclusion
We proposed a method to estimate the probabilities harboring csPCa for patients who underwent prostate MRI examinations, which allows us to understand the PI-RADS diagnostic performance with several metrics.

Clinical relevance statement
The reported estimated performance metrics are expected to aid in understanding the true diagnostic value of PI-RADS in the entire prostate MRI population performed with clinical suspicion of prostate cancer.

Key Points

Calculating performance metrics only from patients who underwent prostate biopsy may be biased due to biopsy selection criteria, especially in PI-RADS 1–2.

The estimated area under the receiver operating characteristic curve of PI-RADS in the entire prostate MRI population ranged from 0.78 to 0.81 at three facilities.

The estimated statistics are expected to help us understand the true PI-RADS performance and serve as a reference for future studies.

Graphical Abstract
Peri-implant bone regeneration in pigs
Authors: Shanbhag Siddharth , Sanz-Esporrin Javier , Kampleitner Carina , Lie Stein-Atle , Gruber Reinhard , Mustafa Kamal , Sanz Mariano 
Published: November 2024

Abstract
Purpose
To review the current literature to answer the focused question: in the experimental pig model (population), which types of peri-implant bone defects (exposure) have been used evaluate different modes of therapy and what is their capacity for spontaneous healing and regeneration (outcome)?

Methods
Following PRISMA guidelines, electronic databases were searched for studies reporting peri-implant bone defects in the maxillae or mandibles of pigs. Those studies which reported a control group of untreated defects with assessment of spontaneous regeneration [new bone area (BA)] and/or re-osseointegration [new bone-to-implant contact (BIC)] via quantitative radiography or histomorphometry were included in a random effects meta-analysis for the outcomes BA and BIC.

Results
Overall, 21 studies, mostly performed in the mandibles of minipigs, were included. Most studies reported ‘acute’ intrabony (circumferential and/or dehiscence; n = 12) or supra-alveolar defects (horizontal; n = 4). Five studies attempted to induce ‘chronic’ peri-implantitis lesions using ligatures with conflicting results. Meta-analyses revealed pooled estimates (with 95% confidence intervals) of 48.07% BIC (30.14–66%) and 64.31% BA (42.71–85.91%) in intrabony defects, and 52.09% BIC (41.83–62.35%) and 28.62% BA (12.97–44.28%) in supra-alveolar defects. Heterogeneity in the meta-analysis was high (I2 > 90%).

Conclusion
Current evidence for peri-implant bone regeneration in pigs is mainly based on acute intrabony defects, which demonstrate a high capacity for spontaneous regeneration and re-osseointegration. The evidence for chronic peri-implantitis is limited and does not clearly indicate a spontaneous progression of the disease in this animal model.