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Selective regulation of β2AR-mediated effects on cellular signaling mechanisms is governed by the estrogen receptor status of the breast cancer cell lines.3 days agoSympathetic noradrenergic stimuli are transduced at the systemic and cellular level through multiple adrenergic receptor subtypes, the predominant of which is the β2-adrenoceptor (β2-AR). In female-specific hormone-sensitive cancers like breast cancer, the effects of adrenergic stimulation and altered hormone sensitivity on cancer cell survival signaling in the context of estrogen receptor (ER) status-dependent cellular responsiveness remain incompletely understood. ER-positive (MCF-7) and ER-negative (MDA-MB-231) breast cancer cell lines were cultured in vitro and treated with the β2-AR specific agonist terbutaline (10- 6 M and 10- 9 M) and non-selective β-AR antagonist propranolol (10- 5M) to examine their effects on proliferation by cell cycle analysis, expression of pro-angiogenic (VEGF-A, VEGF-C) and signaling (p-ERK, p-CREB) molecules by ELISA, nitric oxide (NO) production by Griess assay, and miRNA expression (miR-21, miR-191) by RT-qPCR. Terbutaline elicited distinct and opposing cellular responses depending on ER status, enhancing proliferation, VEGF-C expression, miR-191 levels, and p-ERK signaling in ER-positive MCF-7 cells, while attenuating proliferation, VEGF-C expression, miR-191 levels, and p-ERK signaling in ER-negative MDA-MB-231 cells. In contrast, p-CREB signaling was enhanced in both cell lines. VEGF-A expression was downregulated in both cell lines, whereas NO production and miR-21 expression were increased in an ER-independent manner, suggesting involvement of β-adrenergic signaling mechanisms beyond direct ER mediation. Propranolol significantly attenuated terbutaline-induced effects in both cell lines, with greater magnitude of inhibition observed in ER-positive cells. These findings demonstrate that β2-AR-mediated regulation of proliferation, angiogenic signaling, and epigenetic modulators in breast cancer cells is differentially modulated by ER status, likely through selective engagement of ERK- and CREB-dependent signaling pathways. While ER-dependent crosstalk contributes to divergent outcomes, ER-independent β-adrenergic mechanisms may also play a role, underscoring the complexity of adrenergic signaling in breast cancer progression.CancerPolicy
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MicroRNA circuits and regulatory networks: emerging therapeutic paradigm.3 days agoMicroRNAs (miRNAs) are small non-coding RNAs whose function is to regulate gene expression post-transcriptionally. Transcription factors (TFs) are the DNA-binding proteins responsible for activation or repression of a gene. Together, miRNAs and TFs form regulatory networks that modulate cellular homeostasis. In these regulatory networks, these TFs often regulate the expression of miRNAs, and in turn, miRNAs regulate the expression of TFs, thus forming feedback and feedforward loops. These loops and regulatory networks allow precise control over gene expression patterns by enabling accurate signal processing. Utilizing mathematical modelling and machine learning approaches helps understand the global structure of these networks. These reveal cellular fate selection, stress adaptation, disease development, and gaining insights into these interconnected regulatory systems opens new prospects for novel biomarker discovery and therapeutic approaches in a variety of disciplines, including cancer and immunotherapy.CancerPolicy
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Making Interventions More Effective: Changes in Theoretical Constructs During Delivery of a Peer-Led Physical Activity Program for Breast Cancer Survivors.3 days agoTheory-based physical activity (PA) interventions improve moderate to vigorous physical activity (MVPA) among breast cancer survivors, yet limited research has examined when psychosocial changes occur during intervention delivery. Understanding temporal changes in theoretical constructs during PA adoption may enhance intervention delivery and outcomes. The purpose of this study is to examine longitudinal changes in self-efficacy, self-regulation and affect (intrapersonal constructs from Social Cognitive Theory) and social support (interpersonal construct) during a 12-week theory-based PA program (webMFT) and their association with participants' active minutes (measured by Fitbit) over 12 weeks and intervention engagement (receipt of 12 weekly peer coaching calls).
In a randomized controlled trial with 61 participants, 30 were randomized to receive webMFT (mean age = 58.1 [SD = 8.55], 1.40 years post-diagnosis [SD = 0.5], 80% Stage 0-1 cancer, 80% White) delivered by 10 peer coaches. Only the webMFT participants were assessed; the comparison group (MVPA Tracking) was not included in the analyses. webMFT participants received a Fitbit tracker and weekly PA coaching calls tailored to Fitbit PA data. At baseline, 4, 8 and 12 weeks, they completed questionnaires assessing multidimensional self-efficacy (task, coping, scheduling), self-regulation skills, affective response and social support for PA. Mixed effects regression models examined changes in constructs and their association with Fitbit active minutes/week and intervention engagement.
Increases in total self-efficacy, scheduling self-efficacy, positive affect and social support from family and friends were significantly associated with participants' PA over 12 weeks. There were no significant associations between changes in self-regulation skills, task or coping self-efficacy with PA. Improvements in total self-efficacy, scheduling self-efficacy, self-regulation, affective response and family social support were positively associated with intervention engagement.
Participants' self-efficacy, specifically, for scheduling PA, positive affect and social support for PA adoption and intervention engagement merit future examination.CancerPolicy -
[Expression of Concern] MicroRNA‑195‑5p is a potential diagnostic and therapeutic target for breast cancer.3 days agoFollowing the publication of the above article, a concerned author drew to the authors' attention that, regarding the cell migration assay experiments shown in Fig. 4 on p. 1099, Fig. 4B and C, showing the results of the 'NC' and 'Mock' experiments, contained an overlapping section of data, suggesting that these data panels were derived from the same original source where different experiments were intended to have been portrayed. The authors have been contacted by the Editorial Office to offer an explanation for this apparent anomaly in the presentation of the data in this paper, and we are awaiting their response. Owing to the fact that the Editorial Office has been made aware of this potential issue concerning the scientific integrity of this paper, we are issuing an Expression of Concern to notify readers of this potential problem while the Editorial Office continues to investigate this matter further. [Oncology Reports 31: 1096‑1102, 2014; DOI: 10.3892/or.2014.2971].CancerPolicy
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Top 20 Research Studies of 2025 for Primary Care Physicians.3 days agoThis article summarizes the top 20 research studies of 2025 identified as POEMs (patient-oriented evidence that matters). Treating male sex partners of female patients with oral and topical medication reduces recurrence of bacterial vaginosis. Anti-influenza drugs do not reduce hospitalizations or mortality. COVID-19 vaccines still improve mortality and reduce hospitalizations. Influenza vaccines are safe in pregnancy. Vaginal estrogen appears to be safe in breast cancer survivors. Women with normal bone density given zoledronic acid every 5 years have fewer fractures. Early post-partum insertion of a long-acting reversible contraceptive is associated with fewer pregnancies vs delayed insertion. Early medication abortion before pregnancy confirmation is safe and effective. After stent placement in patients with atherosclerotic coronary vascular disease who are taking an anticoagulant, adding aspirin worsens outcomes. After catheter ablation for atrial fibrillation, discontinuing anticoagulants after 1 year is safe if atrial arrhythmia does not recur, whereas left atrial appendage closure is superior to oral anticoagulation. For patients with provoked venous thromboembolism and at least one ongoing risk factor, 12 months of apixaban is better than 3 months. Clopidogrel is slightly more effective than aspirin for the secondary prevention of myocardial infarction and stroke over 3 years. Intensive blood pressure lowering decreases cardiovascular events but increases rates of hypotension and syncope, and there are concerns about the applicability of the data to the United States. Duloxetine, milnacipran, and pregabalin provide meaningful pain reduction in adults with fibromyalgia. Amyloid-directed monoclonal antibodies do not provide clinically meaningful cognitive benefits and may cause harms. Bright light therapy is effective for nonseasonal depression. Water exposure 6 hours after cutaneous surgery does not increase the risk of complications. A meta-analysis of platelet-rich plasma injections for knee osteoarthritis concluded that high-quality studies found no meaningful pain improvement. Using an oral challenge to rule out sulfonamide allergy is safe when used with a risk assessment tool.Chronic respiratory diseaseAccessCare/Management
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Respiratory viral and bacterial co-infections in adults in acute care: A multiplex PCR-based study.3 days agoData on the clinical significance of viral-bacterial co-detection by molecular methods in adults is limited. We aimed to determine how often respiratory viruses and bacteria are co-detected in acutely ill adults and whether co-detection is associated with worse clinical outcomes than detection of a virus or bacterium alone.
We prospectively enrolled 998 adult patients presenting to the emergency department with symptoms of respiratory infection, fever, chest pain, or poor general condition. Nasal swab samples were taken at entry and analysed by multiplex PCR for 16 respiratory viruses. PCR for 7 bacterial pathogens was performed later on 912 frozen-thawed samples. Medical records were reviewed for the clinical outcomes. Analysis of variance (ANOVA) was used to compare the differences in CRP and age between detection groups. The risk of major outcomes was evaluated using multivariate logistic regression.
Both viral and bacterial PCR were positive in 36 of 912 patients (4%). The most common virus in the Co-detection group was rhinovirus (21/36, 58%) and the most common bacterium Streptococcus pneumoniae (20/36, 56%). The patients in the Co-detection group were younger than those in the Sole bacteria group, who in turn were younger than those in the Sole virus group. Relative to the Negative group, the risk of pneumonia was highest in the Sole bacteria group (aOR 3.53, p < 0.01) and lower, though still elevated, in the Co-detection group (aOR 2.36, p = 0.03). The risk for antibiotic treatment during 30-day follow-up was greatest in the Co-detection group (aOR 4.42), followed by the Sole bacteria (aOR 2.40) and Sole virus (aOR 2.15) groups (all p < 0.01). There was no significant difference between the groups in the risk of death or ICU care.
Viral and bacterial co-detection was rare in acutely ill adults. Although co-detection was associated with the highest risk of antibiotic treatment, it did not carry the highest risk of pneumonia and was not associated with death or ICU admission. Routine use of multiplex PCR for detecting respiratory viral and bacterial pathogens is therefore unlikely to add clinical value in this population. Larger cohorts powered for severe outcomes and real-time result reporting, are needed to determine whether respiratory viral bacterial testing can meaningfully guide clinical management.Chronic respiratory diseaseAccessCare/ManagementAdvocacy -
Asthma Intervention with Residential Ventilation and Air Cleaner (AIRVAC) Study: A 4-arm parallel-group randomized controlled trial protocol.3 days agoEvidence linking exposure to airborne particulate and gaseous pollutants, as well as mold spores, with asthma control and severity is well established. A growing body of literature has demonstrated that ventilation and air filtration can improve indoor air quality (IAQ); however, clinical evidence on their comparative health impacts remains limited. Therefore, this trial aims to evaluate the long-term effectiveness of energy recovery ventilators (ERVs) and portable air cleaners (PACs) in reducing indoor air pollutants and mold levels and improving health outcomes in individuals with asthma. Secondary objectives includes associations between housing conditions, occupant behaviors, indoor environmental exposures, and asthma-related health outcomes.
The AIRVAC study is a single-blind, placebo-controlled, 4-arm, parallel-group, randomized controlled trial, with a pre-intervention period of up to 1 year and a 1-year post-intervention period. Children aged 5-17 years and adults with physician-diagnosed asthma will be recruited from more than 80 households across the Dallas-Fort Worth (DFW) area in Texas. Following the pre-intervention period, each household will be randomized to receive one of four different interventions midway through the study: (1) active ERVs, (2) sham ERVs, (3) active PACs, and (4) sham PACs. Primary health outcomes include asthma control; secondary outcomes include pulmonary function, asthma-related quality of life, stress, and sleep quality. Initial housing assessments will be conducted prior to the pre-intervention period to characterize occupant behaviors and housing-related factors that may contribute to asthma exacerbations and affect ERV installation. Environmental exposures will be assessed by combining measurements of indoor and outdoor air pollutants, including particulate matter (PM), nitrogen dioxide (NO2), carbon monoxide (CO), and volatile organic compounds (VOCs), as well as temperature, relative humidity, and indoor and outdoor mold, using low-cost and research-grade air quality sensors and mold sampling methods.
Findings from the AIRVAC study will provide important evidence on the comparative effects of residential ventilation and air cleaning interventions on IAQ, mold, and asthma-related health outcomes among children and adults with asthma. The study will also examine the relationships among housing characteristics, occupant behaviors, indoor environmental exposures, and asthma-related health outcomes, while providing insights into the operation and performance of residential ventilation and air cleaning interventions in vulnerable households.Chronic respiratory diseaseAccessCare/ManagementAdvocacy -
Healthy Trust and Pandemic Readiness in the Context of Messenger RNA Vaccines: Protocol for a Sequential Deliberative Dialogue Study.3 days agoPandemics threaten economies, security, and public health, requiring strong global and local collaboration and coordination. Public receptivity to emergent vaccine technologies is essential to pandemic readiness. Although messenger RNA (mRNA) vaccines offer rapid adaptability and hold promise, their use during the COVID-19 pandemic was met with polarizing debates that raise questions about the conditions needed to support acceptable and equitable use of new vaccines.
This deliberative dialogue study aims to generate consensus on how to ensure informed, accessible public engagement and strengthen public trust in a climate of divisiveness and misinformation, disinformation, and malinformation. Using mRNA vaccines as a case study, the project's specific research objective is to seek insights into what people believe is needed for public understanding, equitable access, and acceptance of emerging vaccine technologies.
Using a sequential deliberative dialogue design, this study invites individuals with significant influence on pandemic readiness and those most likely to be disproportionately affected by related decisions into reflective, conversational, workshop-style online events and self-led dialogues. Dialogues and guiding questions are informed by a knowledge synthesis on what is unknown about mRNA vaccine public sentiments based on a rapid review, an environmental scan, consultations with experts across sectors, and ongoing updates from the dialogues. Data will be analyzed in situ in an iterative and collaborative synthesis of general agreements between dialogue contributors in response to guiding questions and emerging themes. Dialogue reports will be drafted by the research team based on observational notes, transcripts, and video recordings and reviewed by contributors. In summative dialogues, the research team will present main threads of dialogue, responding to research objectives and newly identified knowledge gaps and collecting input to inform dialogue outputs.
This study was funded in May 2025. As of June 2026, we have conducted 10 deliberative dialogues and supported 1 self-led dialogue, engaging 77 contributors across sectors and disciplines. We held 2 summative dialogues with 18 attendees, where we presented the main threads of dialogue as identified by the research team through collaborative analysis. We have started incorporating input from closing dialogues into the final reports and expect to publish the results in the second half of 2026, both as lay-language reports and peer-reviewed manuscripts.
This protocol outlines a consensus-building process capable of deepening the understanding of vaccine hesitancy and strengthening pandemic readiness and public trust in Canada. Dialogues are expected to provide general agreements on how to enhance science and health literacy, tailor communications considering historical inequities, respond to the needs of health care workers, and navigate polarization around vaccination. By creating space for shared learning and collective insight, this study supports the rebuilding of trust in public health institutions as they adapt to evolving societal expectations.Chronic respiratory diseaseAccessAdvocacy -
Predictors of Treatment Adherence in Outpatients With Chronic Obstructive Pulmonary Disease: Cross-Sectional Study.3 days agoGaps in knowledge, inhalation skills, and adherence continue to hinder effective chronic obstructive pulmonary disease (COPD) management.
The study was conducted to describe the status of COPD-related knowledge, practical skills for inhalation and breathing exercises, and treatment adherence among patients with COPD and to identify the relationships between these variables.
A cross-sectional study was conducted among 420 outpatients with COPD. Data were collected in 2 rounds, including interviews to assess patients' knowledge and treatment adherence and checklist-based observations of patients' practical skills. Multivariable logistic regression analysis was used to evaluate the associations between knowledge and practical skills and the status of treatment adherence.
A total of 420 outpatients with COPD were included; 331 (78.8%) participants had inadequate COPD-related knowledge, 268 (63.8%) demonstrated adequate practical skills, and 155 (36.9%) achieved overall treatment adherence. In multivariable logistic regression, higher knowledge scores were associated with better treatment adherence (adjusted odds ratio [aOR] 1.20, 95% CI 1.06-1.31; P=.001). Participants who correctly performed inhaler-use techniques were more likely to be adherent than those with incorrect technique (aOR 3.10, 95% CI 2.10-4.70; P=.001). Likewise, adequate breathing-exercise skills were associated with higher adherence (aOR 1.70, 95% CI 1.08-2.71; P=.02).
Higher COPD-related knowledge and better practical skills in inhaler use and breathing exercises were associated with better treatment adherence among outpatients with COPD. Because of the cross-sectional design, these findings indicate associations rather than causal relationships. These observed associations may help inform future intervention studies evaluating patient education and skill-based training, although their effectiveness should be confirmed in longitudinal or interventional studies.Chronic respiratory diseaseAccessCare/ManagementAdvocacy -
Strategic health policy and health system resilience in protracted crisis settings: policymaker perspectives from Yemen.3 days agoHealth system resilience is often described through the World Health Organization building blocks, yet in protracted crises it depends on whether governance, financing, workforce, information systems, service delivery, and accountability can convert crisis response into institutional reform.
This study examines how far Yemen's health system responses to prolonged conflict, economic decline, disease outbreaks, and COVID-19 progressed beyond absorptive and adaptive resilience toward transformative resilience, and how strategic health policy across the building blocks shaped this transition.
We conducted 30 in-depth interviews with national and subnational policymakers and health leaders in Yemen between May and July 2025. Data were analysed in ATLAS.ti 25 using framework-informed thematic analysis that combined a priori categories from the World Health Organization health system building blocks and resilience capacities with inductively developed empirical codes.
Yemen demonstrated externally buffered absorptive capacity sufficient to prevent complete system collapse, together with uneven and localised adaptation through crisis committees, donor-supported financing, temporary workforce mobilisation, intensified surveillance, oxygen and isolation capacity, and referral workarounds. However, these responses were largely reactive, donor-dependent, and unevenly institutionalised. Transformative resilience remained constrained by fragmented authority, under-protected recurrent financing, workforce instability, weak data-to-decision pathways, limited referral governance, and the absence of formal learning-to-reform mechanisms.
Yemen's experience shows that resilience in protracted crisis settings should be judged not only by the survival of repeated shocks, but by whether absorptive and adaptive gains are converted into institutional capability through strategic policy alignment across the health system.Chronic respiratory diseaseAccessPolicyAdvocacy